[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"small-lymphocytic-lymphoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:small-lymphocytic-lymphoma":28},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,54,0,25,[9,42,65,94,121,144,169,203,223,270,295,320,345,374,400,438,460,482,515,539,560,583,602,634,661],{"id":10,"slug":11,"hasResults":12,"nctId":13,"briefTitle":14,"officialTitle":15,"acronym":4,"eligibilityCriteria":16,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":30,"lastUpdatePostDateStruct":31,"startDateStruct":34,"completionDateStruct":36,"leadSponsor":38,"locationsCount":41},"100383227","phase-3-testing-early-treatment-for-patients-with-high-risk-chronic-lymphocytic-leukemia-cll-or-small-lymphocytic-leukemia-sll-evolve-cllsll-study-100383227",false,"NCT04269902","Testing Early Treatment for Patients With High-Risk Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL), EVOLVE CLL\u002FSLL Study","Randomized, Phase III Study of Early Intervention With Venetoclax and Obinutuzumab Versus Delayed Therapy With Venetoclax and Obinutuzumab in Newly Diagnosed Asymptomatic High-Risk Patients With Chronic Lymphocytic Leukemia\u002FSmall Lymphocytic Lymphoma (CLL\u002FSLL): EVOLVE CLL\u002FSLL Study","Inclusion Criteria:\n\n* Participants must have a confirmed diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (collectively referred to as CLL throughout) according to the 2018 International Workshop on CLL. Participants must have been diagnosed within 18 months prior to registration\n* Participants must have CLL-International Prognostic Index (CLL-IPI) score \\>= 4 and\u002For complex cytogenetics (defined as 3+ chromosomal abnormalities)\n* Cytogenetic AND\u002FOR FISH analyses must be completed at a Clinical Laboratory Improvement Act (CLIA)-approved (or laboratories accredited under Accreditation Canada Diagnostics to conduct FISH analyses) laboratory within 18 months prior to registration. At minimum, FISH panel should use probes to detect for abnormalities in chromosomes 13q, 12, 11q, and 17p\n* TP53 gene mutation analysis performed at any CLIA-approved (or laboratories accredited under Accreditation Canada Diagnostics) lab (if completed) must be obtained within 18 months prior to registration. This sequencing test is distinct from FISH studies for del(17p)\n\n  * Note: TP53 gene mutation analysis is recommended but not required if the participant meets disease-related study criteria via a combination of risk factors that totals a score of 4 on the CLL-IPI score and\u002For has complex cytogenetics completed\n* Immunoglobulin heavy chain locus variable (IgVH) gene mutation analysis performed at any CLIA-approved lab (or laboratories accredited under Accreditation Canada Diagnostics) must be obtained prior to registration (at any time prior to registration)\n* Serum beta-2 microglobulin level must be obtained within 28 days prior to registration\n* Participants must not meet any of the IWCLL specified criteria for active CLL therapy\n* Treatment with high dose corticosteroids and\u002For intravenous immunoglobulin for autoimmune complications of CLL must be complete at least 4 weeks prior to enrollment\n* Steroids used for treatment of conditions other than CLL\u002FSLL must be at a dose of at most 20 mg\u002Fday of prednisone or equivalent corticosteroid at the time of registration\n* Prior therapy with anti CD20 monoclonal antibodies is not allowed\n* Participants must not have received or be currently receiving any prior CLL-directed therapy, including non-protocol-related therapy, anti-cancer immunotherapy, experimental therapy (with exception of agents approved for emergency access use for the prevention or treatment of coronavirus disease 2019 \\[COVID-19\\]), or radiotherapy\n* Participants must not be receiving or planning to receive any other investigational agents before completing protocol therapy\n* Participants must be \\>= 18 years of age\n* Participants must have Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 2\n* Platelet count \\>= 100,000\u002Fmm\\^3 within 28 days prior to registration\n* Absolute neutrophil count (ANC) \\>= 1,000\u002Fmm\\^3 within 28 days prior to registration\n* Creatinine clearance \\>= 30mL\u002Fmin (by Cockcroft Gault) within 28 days prior to registration\n* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \\\u003C 3.0 x upper limit of normal (ULN) within 28 days prior to registration\n* Total bilirubin =\\\u003C 2.0 x ULN (or 5.0 x ULN if the participant has a history of Gilbert's disease), within 28 days prior to registration\n* Participants must be able to take oral medications\n* Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* Participants with history of malignancy are allowed providing the cancer has not required active treatment within 2 years prior to registration (hormonal therapy is permissible). The following exceptions are permissible: basal cell, squamous cell skin, or non-melanomatous skin cancer, in situ cervical cancer, superficial bladder cancer not treated with intravesical chemotherapy or Bacillus Calmette-Guerin (BCG) within 6 months, localized prostate cancer treated with surgical resection and\u002For radiation only or requiring no more than chronic hormonal therapy, or prostate cancer with Gleason score ≤ 6, or localized breast cancer treated with surgical resection and\u002For radiation only or requiring no more than chronic hormonal therapy\n* Participants must not have current, clinically significant gastrointestinal malabsorption, in the opinion of treating doctor\n* Participants must not have cirrhosis\n* Obinutuzumab has been associated with hepatitis reactivation. Participants must not have uncontrolled active infection with hepatitis B or C. Participants with latent hepatitis B infection must agree to take prophylaxis during and for 6 months following active protocol therapy with V-O.\n\n  * Active infection with hepatitis B or C:\n\n    * Active infection is defined as detectable hepatitis B deoxyribonucleic acid (DNA) or hepatitis C ribonucleic acid (RNA) by quantitative polymerase chain reaction (PCR).\n  * Latent infection with hepatitis B:\n\n    * Latent infection is defined as meeting all of the following criteria:\n\n      * Hepatitis B surface antigen positive\n      * Anti-hepatitis B total core antibody positive\n      * Anti-hepatitis IgM core antibody undetectable\n      * Hepatitis B PCR undetectable\n    * Participants with latent hepatitis B infection must agree to take prophylaxis with anti-hepatitis agents during and for 6 months following active protocol therapy with V-O.\n    * Participants who have received intravenous immunoglobulin (IVIG) therapy within 6 months who are hepatitis B core total antibody positive but PCR undetectable are not mandated to take prophylaxis\n* Participants must not have had major surgery within 30 days prior registration or minor surgery within 7 days prior to registration. Examples of major surgery include neurosurgical procedures, joint replacements, and surgeries that occur inside the thoracic or abdomino-pelvic cavities. Examples of minor surgery include dental surgery, insertion of a venous access device, skin biopsy, or aspiration of a joint. If a participant has had a bone marrow biopsy for diagnosis or evaluation of CLL, this will not exclude the participant from registration to the study. If there is a question about whether a surgery is major or minor, this should be discussed with the Study Chair\n* Participants must not have known bleeding disorders (e.g., von Willebrand's disease or hemophilia)\n* Participants must not have a history of stroke or intracranial hemorrhage within 6 months prior to enrollment\n* Participants must not require continued therapy with a strong inhibitor or inducer of CYP3A4\u002F5, as venetoclax is extensively metabolized by CYP3A4\u002F5\n* Participants must not have uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura\n* Participants must not have any currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification\n* Participants must not have a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment\n* Participants must not be pregnant or nursing, as there are no safety data available for these drug regimens during pregnancy. Women\u002Fmen of reproductive potential must have agreed to use an effective contraceptive method. A woman is considered to be of \"reproductive potential\" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, \"effective contraception\" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he\u002Fshe is responsible for beginning contraceptive measures\n* Participants must agree to have specimens submitted for translational medicine (MRD) as outlined\n* Participants must be offered the opportunity to participate in specimen banking for future research as outlined.\n\n  * NOTE: With participant's consent, the site must follow through with specimen submission as outlined\n* Participants who are able to complete patient reported outcome (PRO) forms in English, Spanish, French, German, Russian or Mandarin must be offered the opportunity to participate in the quality of life assessments. (Those participants who are unable to read and write in English, Spanish, French, German, Russian or Mandarin may be registered to S1925 without contributing to the quality of life portion of the study.)\n* Participants must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines\n* NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system","ALL","18 Years",{"count":20,"type":21},247,"ESTIMATED","INTERVENTIONAL",[24],"PHASE3","This phase III trial compares early treatment with venetoclax and obinutuzumab versus delayed treatment with venetoclax and obinutuzumab in patients with newly diagnosed high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Starting treatment with the venetoclax and obinutuzumab early (before patients have symptoms) may have better outcomes for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma compared to starting treatment with the venetoclax and obinutuzumab after patients show symptoms.",[27,28],"Chronic Lymphocytic Leukemia","Small Lymphocytic Lymphoma","RECRUITING","2026-07-01",{"date":32,"type":33},"2026-07-02","ACTUAL",{"date":35,"type":33},"2021-03-02",{"date":37,"type":21},"2028-10-01",{"name":39,"class":40},"National Cancer Institute (NCI)","NIH",631,{"id":43,"slug":44,"hasResults":12,"nctId":45,"briefTitle":46,"officialTitle":47,"acronym":4,"eligibilityCriteria":48,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":49,"targetDuration":4,"studyType":22,"phases":50,"briefSummary":52,"conditions":53,"keywords":4,"overallStatus":54,"whyStopped":4,"lastUpdateSubmitDate":55,"lastUpdatePostDateStruct":56,"startDateStruct":57,"completionDateStruct":59,"leadSponsor":61,"locationsCount":64},"100635774","phase-2-nemtabrutinib-and-venetoclax-for-the-treatment-of-patients-with-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma-100635774","NCT07557056","Nemtabrutinib and Venetoclax for the Treatment of Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma","A Phase 2 Study of Nemtabrutinib and Venetoclax as Frontline Treatment for Chronic Lymphocytic Leukemia (CLL)","Inclusion Criteria:\n\n* Confirmed diagnosis of CLL\u002FSLL meeting criteria established in the 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines\n* Is an individual of any sex\u002Fgender, who is at least 18 years of age on the day of signing informed consent\n* Participants must have treatment-naïve CLL\u002FSLL. Palliative loco-regional radiotherapy, rituximab for autoimmune conditions, or corticosteroids for symptom control will not be considered prior therapy\n* Participants must meet criteria for treatment as defined by 2018 iwCLL guidelines which includes at least one of the following criteria:\n\n  * Massive (\\>= 6 cm below the costal margin), progressive or symptomatic splenomegaly\n  * Massive nodes (\\>= 10 cm) or progressive or symptomatic lymphadenopathy\n  * Progressive lymphocytosis with a lymphocyte doubling time \\\u003C 6 months or an increase of \\>= 50% over a 2 month period\n  * Autoimmune anemia and\u002For thrombocytopenia that is poorly responsive to standard therapy\n  * Symptomatic or functional extranodal involvement (e.g. skin, kidney, lung, spine)\n  * Constitutional symptoms, which include any of the following:\n\n    * Unintentional weight loss of 10% or more within 6 months\n    * Significant fatigue\n    * Fevers \\> 100.5 degrees Fahrenheit (F) for 2 weeks or more without evidence of infection\n    * Night sweats \\>= 1 month without evidence of infection\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention\n* Adequate bone marrow independent of growth factor support or infusion support at screening unless evidence shows that the cytopenia(s) is due to marrow involvement by CLL\u002FSLL and\u002For disease-related immune thrombocytopenia, or anemia. If cytopenias are due to disease in the bone marrow any degree of cytopenias are allowed. Patients with active uncontrolled autoimmune cytopenias are excluded\n* Absolute neutrophil count (ANC) \\>= 1000\u002Fmm\\^3\n* Platelets \\>= 50,000\u002Fmm\\^3\n* Hemoglobin \\>= 8 g\u002FdL\n* Willing and able to participate in all required evaluations and procedures in this study protocol\n* Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information\n* Participants assigned male sex at birth: If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:\n\n  * Nemtabrutinib: 12 days\n  * Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR\n  * Uses contraception as detailed below unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel's review of the participant's medical records, medical examination, or medical history interview) as detailed below:\n  * Uses a penile\u002Fexternal condom plus nonparticipant of childbearing potential who is not currently pregnant and should also be advised of the benefit for that partner to use an additional method of contraception, as a condom may break or leak.\n\n    * Note: Participants capable of producing ejaculate whose partner is pregnant or breastfeeding must agree to use penile\u002Fexternal condom during each episode of sexual activity in which the partner is at risk of drug exposure via ejaculate.\n  * Contraceptive use by participants capable of producing sperm should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed\n* Participants assigned female sex at birth: A participant assigned female sex at birth is eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies:\n\n  * Is not a person of childbearing potential (POCBP) OR\n  * Is a POCBP and:\n\n    * Uses a contraceptive method that is highly effective (with a failure rate of \\\u003C 1% per year), with low user dependency, or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:\n\n      * Nemtabrutinib: 1 month\n    * The investigator should evaluate the potential for contraceptive method failure (i.e., noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by POCBPs should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed.\n    * Has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for urine test) or 72 hours (for serum test) before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.\n    * Abstains from breastfeeding during the study intervention period and for at least 30 days after study intervention with nemtabrutinib.\n    * Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy\n* The ability to swallow and retain oral medication.\n\n  * NOTE: Administration of nemtabrutinib is not permitted through a percutaneous endoscopic gastro-jejunostomy (J-PEG) tube\n* Participants who are hepatitis B surface antigen (HbsAg) positive are eligible if they have received hepatitis B viral (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to screening.\n\n  * Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. Hepatitis B screening tests, including HBsAg and anti-HBc (hepatitis B core), are required for all participants\n* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.\n\n  * Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.\n  * Hepatitis C screening tests are not required unless:\n\n    * Known history of HCV infection\n    * As mandated by local health authority\n* Participants with human immunodeficiency virus (HIV) are eligible if they meet ALL of the following criteria:\n\n  * The CD4 count is \\> 350 cells\u002FìL at screening\n  * The HIV viral load is below the detectable level as per locally available testing\n  * Are on a stable antiretroviral therapy (ART) regimen for at least 4 weeks prior to study entry\n  * NOTE: ART includes drugs, which are NOT strong CYP3A4 inducers (participants receiving ART that are strong CYP3A4 inducers are not eligible to be included in the study).\n  * HIV screening tests are not required unless:\n\n    * Known history of HIV infection\n    * As mandated by local health authority\n  * Are compliant with their ART\n  * NOTE: If the participant has had an acquired immunodeficiency syndrome (AIDS) defining opportunistic infection in the past 12 months prior to screening, they are not eligible to be included in the study\n* Absolute neutrophil count (ANC) \\>= 1000\u002FuL\n\n  * Growth factor and\u002For transfusion support is permissible to stabilize participant prior to study treatment if needed.\n  * No lower limit if cytopenia is related to bone marrow involvement\n* Platelets \\>= 50000\u002FuL\n\n  * Growth factor and\u002For transfusion support is permissible to stabilize participant prior to study treatment if needed.\n  * No lower limit if cytopenia is related to bone marrow involvement\n* Hemoglobin \\>= 8 g\u002FdL\n\n  * Growth factor and\u002For transfusion support is permissible to stabilize participant prior to study treatment if needed.\n  * No lower limit if cytopenia is related to bone marrow involvement\n* Creatinine clearance (CrCl) \\>= 30mL\u002Fmin\n* Total bilirubin ≤ 1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin levels \\> 1.5 × ULN\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) =\\\u003C 2.5 x ULN (=\\\u003C 5 x ULN for participants with liver metastases)\n* International normalized ratio (INR) OR prothrombin time (PT) activated partial thromboplastin time (aPTT) =\\\u003C 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants\n\nExclusion Criteria:\n\n* Subject with other malignancies that are associated with a life expectancy of \\\u003C 2 years or that would confound assessment of toxicity in this study.\n\n  * NOTE: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder\n* Clinically significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification. Note: Subjects with controlled atrial fibrillation can enroll on study\n* Active HBV\u002FHCV infection\n* Inability to swallow oral medication or gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy)\n* Diagnosis of Richter transformation\n* Active central nervous system (CNS) involvement\n* Active infection requiring systemic therapy, including intravenous (IV) antibiotics during screening. Participants may be rescreened followed completion of IV antibiotic course\n* AIDS defining opportunistic infection in the past 12 months prior to screening\n* History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator\n* Corrected QT (QTc) prolongation (defined as a Fridericia-corrected QT interval \\[QTcF\\] \\> 450 msecs) or other significant electrocardiogram (ECG) abnormalities including second degree atrioventricular (AV) block type II, third degree AV block, or bradycardia (ventricular rate less than 50 beats\u002Fmin)\n* Known allergy\u002Fsensitivity (\\>= grade 3) to nemtabrutinib or any of the excipients.\n\n  * NOTE: Refer to the investigator brochure (IB) for details regarding excipients for nemtabrutinib\n* History of severe bleeding disorders\n* A POCBP who has a positive urine pregnancy test within 72 hours prior to enrollment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required\n\n  * Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication\n* Prior CLL\u002FSLL directed therapy\n* Currently being treated with the following drugs:\n\n  * P-glycoprotein (P-gp) substrates with a narrow therapeutic index\n  * CYP3A strong inducers\n  * CYP3A strong inhibitors\n  * NOTE: A washout period of at least 5 times the half-life after the last dose of any of the above treatments is required for a participant to be eligible for study enrollment. A list of example in vivo substrates for specific CYP enzymes and P-gp is provided\n  * NOTE: Refer to protocol regarding prohibited concomitant medications and potential drug interactions after participant randomization\n* Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (if prior therapy was a monoclonal antibody) or 5 half-lives before randomization (whichever is longer)\n* Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids\n\n  * Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease, with a 1-week washout, is permitted\n* Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.\n\n  * Note: please refer to protocol for information on COVID-19 vaccines\n* Is currently enrolled on another therapeutic clinical trial. Concurrent enrollment on another therapeutic clinical trial or any trial designed to impact the efficacy of anti-cancer therapy is prohibited\n* Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication\n* Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid)\n* Has an active infection requiring systemic therapy\n* Has not adequately recovered after 4 weeks from major surgery or has ongoing surgical complications.\n\n  * Note: Biopsy and placement of central venous access devices are not considered major surgery\n* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial",{"count":7,"type":21},[51],"PHASE2","This phase II trial tests how well nemtabrutinib and venetoclax work in treating patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Nemtabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cells (a type of white blood cell) in cancers such as CLL or SLL at abnormal levels. This may help keep cancer cells from growing and spreading. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Giving nemtabrutinib in combination with venetoclax may kill more cancer cells in patients with CLL or SLL.",[27,28],"NOT_YET_RECRUITING","2026-06-29",{"date":30,"type":33},{"date":58,"type":21},"2026-09-01",{"date":60,"type":21},"2027-12-31",{"name":62,"class":63},"Jennifer Woyach","OTHER",1,{"id":66,"slug":67,"hasResults":12,"nctId":68,"briefTitle":69,"officialTitle":69,"acronym":4,"eligibilityCriteria":70,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":71,"targetDuration":4,"studyType":22,"phases":73,"briefSummary":75,"conditions":76,"keywords":84,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":55,"lastUpdatePostDateStruct":87,"startDateStruct":88,"completionDateStruct":90,"leadSponsor":92,"locationsCount":64},"100582251","combating-cancer-related-fatigue-a-personalized-supportive-care-program-100582251","NCT06860880","Combating Cancer-Related Fatigue: A Personalized Supportive Care Program","In order to participate in this study a subject must meet all of the eligibility criteria outlined below.\n\nInclusion Criteria:\n\n* Written informed consent was obtained to participate in the study and HIPAA authorization for the release of personal health information.\n* Subjects are willing and able to comply with study procedures based on the judgment of the investigator.\n* Age ≥ 18 years at the time of consent.\n* Confirmed diagnosis of indolent lymphoma, Waldenström's Macroglobulinemia, or Cutaneous T Cell Lymphoma.\n* Significant symptoms of fatigue, as defined by PROMIS Fatigue score \\>50.\n\nExclusion Criteria:\n\n* Other co-existing malignancies.\n* Significant cognitive impairment as defined by Mini-Cog score 0-2 (out of 5) that would prevent understanding of assessments or interventions.\n* Unstable or serious illness (e.g., unstable cardiac arrhythmia, severe anemia\u002Fthrombocytopenia) that would prevent safe participation in an exercise regimen, per the discretion of the treating physician.\n* Individuals who are not able to consume an oral diet, due to swallowing difficulties or other reasons, as this might interfere with the nutritional intervention",{"count":72,"type":21},40,[74],"NA","This health services study will assess a multidisciplinary intervention program directed at fatigue mitigation among patients diagnosed with indolent lymphomas. Specifically, 30 subjects with chronic lymphocytic leukemia\u002Fsmall lymphocytic lymphoma (CLL\u002FSLL) and 10 subjects with Follicular Lymphoma (FL), marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma (LPL), Waldenström's Macroglobulinemia, or Cutaneous T Cell Lymphoma (CTCL) will be included.",[77,78,27,28,79,80,81,82,83],"Indolent Lymphomas","Lymphoma","Follicular Lymphoma","Marginal Zone Lymphoma","Lymphoplasmacytic Lymphoma","Waldenstrom Macroglobulinemia","Cutaneous T Cell Lymphoma",[85,86],"exercise","dietary intervention",{"date":30,"type":33},{"date":89,"type":33},"2025-06-03",{"date":91,"type":21},"2026-12-31",{"name":93,"class":63},"UNC Lineberger Comprehensive Cancer Center",{"id":95,"slug":96,"hasResults":12,"nctId":97,"briefTitle":98,"officialTitle":98,"acronym":4,"eligibilityCriteria":99,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":100,"enrollmentInfo":101,"targetDuration":4,"studyType":103,"phases":4,"briefSummary":104,"conditions":105,"keywords":108,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":114,"lastUpdatePostDateStruct":115,"startDateStruct":117,"completionDateStruct":4,"leadSponsor":119,"locationsCount":64},"100127162","natural-history-study-of-monoclonal-b-cell-lymphocytosis-mbl-chronic-lymphocytic-leukemiasmall-lymphocytic-lymphoma-cllsll-lymphoplasmacytic-lymphoma-lplwaldenstrom-macroglobulinemia-wm-and-splenic-marginal-zone-lymphoma-smzl-100127162","NCT00923507","Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia\u002FSmall Lymphocytic Lymphoma (CLL\u002FSLL), Lymphoplasmacytic Lymphoma (LPL)\u002FWaldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)","-INCLUSION CRITERIA:\n\n1. Diagnosis of CLL\u002FSLL will be made according to the updated criteria of the NCI Working Group.\n\n   * on treatment or previously treated\n   * requiring or nearing first-line treatment\n\n   OR\n\n   Diagnosis of LPL\u002FWM. LPL is defined as the presence of an intertrabecular pattern of bone marrow infiltration by small lymphocytes showing plasmacytoid\u002Fplasma cell differentiation. WM, comprising \\>95% of LPL cases, describes the clinical syndrome of LPL associated with an IgM monoclonal gammopathy of any concentration. The remaining cases may be IgA, IgM, or non-secreting LPL. Immunophenotyping is required for diagnosis\n2. Age greater than or equal to 18 years.\n3. ECOG performance status of 0-2.\n4. Able to comprehend the investigational nature of the protocol and provide informed consent\n\nEXCLUSION CRITERIA:\n\n1\\. None","110 Years",{"count":102,"type":21},1000,"OBSERVATIONAL","Background\n\nThe development of new technologies now allow scientists to investigate the molecular basis and clinical manifestations of monoclonal B cell lymphocytosis (MBL), chronic lymphocytic leukemia(CLL)\u002Fsmall lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL)\u002FWaldenstrom macroglobulinemia (WM), and splenic marginal zone lymphoma (SMZL). Applying these methods in a natural history study can help identify processes involved in disease progression, and possibly lead to the discovery or validation of treatment targets.\n\nObjectives\n\nStudy the history of MBL\u002FCLL\u002FSLL\u002FLPL\u002FWM\u002FSMZL in patients prior to and after treatment. Characterize clinical, biologic and molecular events of disease stability and progression of patients enrolled on this protocol.\n\nEligibility:\n\n* Diagnosis of CLL\u002FSLL and on treatment\u002Fpreviously treated\u002Fnearing treatment\n* Diagnosis of LPL\u002FWM\n* As of February 5, 2025, patients with MBL and SMZL will no longer be enrolled.\n* Age greater than or equal to 18 years.\n* ECOG performance status of 0-2.\n\nDesign\n\nPatients are typically followed every 6 to 24 months in the clinic and have blood drawn. Patients may be asked to undergo additional testing, including bone marrow biopsy and aspiration, lymph node biopsy, positron emission tomography, and CT and MRI scans. Some of these tests (e.g., blood draw) may be required to monitor CLL\u002FSLL and LPL\u002FWM. Other tests (e.g., lymph node biopsy) may not be clinically indicated, but patients may be asked to undergo these procedures for research purposes.\n\nNo treatment will be administered on this study. If a patients requires treatment for their cancer, available NIH clinical trials and alternative treatment options will be discussed with the patient.\n\n...",[82,81,106,28,107],"Monoclonal B-Cell Lymphocytosis","CLL (Chronic Lymphocytic Leukemia)",[109,110,111,112,113,78],"Chronic Lymphocytic Leukemia (CLL)","Monoclonal B Cell Lymphocytosis","Small Lymphocytic Lymphoma (SLL)","Natural History","Leukemia","2026-06-27",{"date":116,"type":33},"2026-06-30",{"date":118,"type":33},"2008-05-29",{"name":120,"class":40},"National Heart, Lung, and Blood Institute (NHLBI)",{"id":122,"slug":123,"hasResults":12,"nctId":124,"briefTitle":125,"officialTitle":126,"acronym":4,"eligibilityCriteria":127,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":128,"targetDuration":4,"studyType":22,"phases":130,"briefSummary":131,"conditions":132,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":133,"lastUpdatePostDateStruct":134,"startDateStruct":136,"completionDateStruct":138,"leadSponsor":140,"locationsCount":143},"100526578","phase-3-a-study-of-nemtabrutinib-mk-1026-versus-comparator-investigators-choice-of-ibrutinib-or-acalabrutinib-in-first-line-1l-chronic-lymphocytic-leukemia-cll-small-lymphocytic-lymphoma-sll-mk-1026-011bellwave-011-100526578","NCT06136559","A Study of Nemtabrutinib (MK-1026) Versus Comparator (Investigator's Choice of Ibrutinib or Acalabrutinib) in First Line (1L) Chronic Lymphocytic Leukemia (CLL)\u002F Small Lymphocytic Lymphoma (SLL) (MK-1026-011\u002FBELLWAVE-011)","A Phase 3, Randomized Study to Compare Nemtabrutinib Versus Comparator (Investigator's Choice of Ibrutinib or Acalabrutinib) in Participants With Untreated Chronic Lymphocytic Leukemia\u002FSmall Lymphocytic Lymphoma (BELLWAVE-011)","Inclusion Criteria:\n\nThe main inclusion criteria include but are not limited to the following:\n\n* Confirmed diagnosis of CLL\u002FSLL and active disease clearly documented to have a need to initiate therapy.\n* Has at least 1 marker of disease burden.\n* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days before randomization.\n* Has the ability to swallow and retain oral medication.\n* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV deoxyribonucleic acid (DNA) viral load before randomization.\n* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV ribonucleic acid (RNA) viral load is undetectable at screening.\n* Participants with human immunodeficiency virus (HIV) who meet ALL eligibility criteria.\n\nExclusion Criteria:\n\nThe main exclusion criteria include but are not limited to the following:\n\n* Has an active hepatitis B virus\u002F hepatitis C virus (HBV\u002FHCV) infection.\n* Has gastrointestinal (GI) dysfunction that may affect drug absorption.\n* Has diagnosis of Richter Transformation or active central nervous system (CNS) involvement by CLL\u002FSLL.\n* Has had acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in the past 12 months before screening.\n* Has clinically significant cardiovascular disease.\n* Has hypersensitivity to nemtabrutinib or contraindication to ibrutinib or acalabrutinib, or any of the excipients.\n* Has history of severe bleeding disorder.\n* Has known additional malignancy that is progressing or has required active treatment within the past 2 years.\n* Has received any systemic anticancer therapy for CLL\u002FSLL.\n* Is currently being treated with p-glycoprotein (P-gp) substrates with a narrow therapeutic index, cytochrome P450 3A (CYP3A) strong or moderate inducers or CYP3A strong inhibitors.\n* Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids.\n* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.\n* Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration.\n* Has active infection requiring systemic therapy, including intravenous (IV) antibiotics during screening.\n* Participants who have not adequately recovered from major surgery or have ongoing surgical complications.",{"count":129,"type":21},1200,[24],"The goal of this study is to evaluate nemtabrutinib compared with investigator's choice of ibrutinib or acalabrutinib in participants with chronic lymphocytic leukemia (CLL)\u002Fsmall lymphocytic lymphoma (SLL) who have not received any prior therapy. The primary hypotheses are that (1) nemtabrutinib is non-inferior to ibrutinib or acalabrutinib with respect to objective response rate (ORR) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 by blinded independent central review (BICR) and (2) nemtabrutinib is superior to ibrutinib or acalabrutinib with respect to progression free survival (PFS) per iwCLL Criteria 2018 by BICR.",[27,28],"2026-06-25",{"date":135,"type":33},"2026-06-26",{"date":137,"type":33},"2023-12-13",{"date":139,"type":21},"2032-09-07",{"name":141,"class":142},"Merck Sharp & Dohme LLC","INDUSTRY",199,{"id":145,"slug":146,"hasResults":12,"nctId":147,"briefTitle":148,"officialTitle":149,"acronym":4,"eligibilityCriteria":150,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":151,"targetDuration":4,"studyType":22,"phases":153,"briefSummary":154,"conditions":155,"keywords":156,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":160,"lastUpdatePostDateStruct":161,"startDateStruct":162,"completionDateStruct":164,"leadSponsor":166,"locationsCount":168},"100557951","phase-2-zanubrutinib-with-obinutuzumab-in-untreated-patients-with-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma-100557951","NCT06544785","Zanubrutinib With Obinutuzumab in Untreated Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma","A Multicenter, Phase 2 Randomized, Open Label Study to Evaluate Zanubrutinib in Combination With Obinutuzumab in Previously Untreated Patients With Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) (GELLC-10-ZANUBIO)","Inclusion Criteria:\n\n1. Adult patients with previously untreated CLL defined following IWCLL criteria (Hallek, 2018).\n2. Must understand and voluntarily sign an informed consent form.\n3. Age ≥ 18 years at the time of signing the informed consent form and must be able to adhere to the study visit schedule and other protocol requirements.\n4. Must have a documented diagnosis of CLL or SLL \\[IWCLL guidelines for diagnosis and treatment of CLL (Hallek, 2018)\\] meeting at least one of the following criteria:\n\n   * Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and\u002For thrombocytopenia.\n   * Massive (i.e. ≥6 cm below the left costal margin) or progressive or symptomatic splenomegaly.\n   * Massive nodes (i.e. ≥10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.\n   * Progressive lymphocytosis with an increase of ≥50% over a 2-month period, or lymphocyte doubling time (LDT) of less than 6 months.\n   * A minimum of any one of the following disease-related symptoms: unintentional weight loss ≥ 10% within the previous 6 months, significant fatigue (i.e., ECOG PS 2 or worse; cannot work or unable to perform usual activities), fevers of greater than 38.0°C for 2 or more weeks without other evidence of infection, or night sweats for more than 1 month without evidence of infection.\n   * Autoimmune complications including anemia or thrombocytopenia poorly responsive to corticosteroids.\n   * Symptomatic or functional extranodal involvement (eg, skin, kidney, lung, spine).\n5. Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2.\n6. Female patients of childbearing potential must practice highly effective methods of contraception initiated prior to first dose of study drug, for the duration of the study, and for ≥ 90 days after the last dose of zanubrutinib and 18 months after last dose of obinutuzumab.\n\n   Male patients are eligible if vasectomized or if they agree to the use of barrier contraception with other applicable highly effective methods described below during the study treatment period and for ≥ 90 days after the last dose of zanubrutinib and 18 months after last dose of obinutuzumab.\n\n   A woman is considered of childbearing potential, ie, fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. Contraception methods include the following:\n   * Combined (estrogen- and progestogen- containing) hormonal contraception associated with the inhibition of ovulation - Oral, intravaginal, or transdermal.\n   * Progestogen-only hormonal contraception associated with the inhibition of ovulation - Oral, injectable, implantable.\n   * An intrauterine device.\n   * Intrauterine hormone-releasing system.\n   * Bilateral tubal occlusion.\n   * Vasectomized partner (provided that the vasectomized partner is the sole sexual partner of the woman of childbearing potential study participant and that the vasectomized partner has received medical assessment of surgical success).\n   * Sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment, starting the day prior to first dose of study drug, for the duration of the study, and for ≥ 90 days after the last dose of zanubrutinib or ibrutinib. Total sexual abstinence should only be used as a contraceptive method if it is in line with the patients' usual and preferred lifestyle. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to investigational medicinal product, and withdrawal are not acceptable methods of contraception.\n\n   Of note, barrier contraception (including male and female condoms with or without spermicide) is not considered a highly effective method of contraception, and, if used, this method must be used in combination with another acceptable method listed above.\n\n   If patient is using hormonal contraceptives such as birth control pills or devices, a barrier method of contraception (eg, condoms) must also be used.\n\n   A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single follicle-stimulating hormone measurement is insufficient.\n7. Female subjects of childbearing potential must have a negative pregnancy test at screening. Females of child bearing potential are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to other causes, including prior chemotherapy, anti-estrogens, or ovarian suppression.\n\nExclusion Criteria:\n\n1. Prior treatment for CLL.\n2. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and\u002For Hepatitis C Virus (HCV) infection. Subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative could be eligible if they have an undetectable HBV DNA (negative polymerase chain reaction (PCR) \\\u003C20 IU). Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded. Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded.\n\n   Per published guidelines (NCCN 2012) or institutional guidelines, patients should be closely monitored for hepatitis B reactivation. Obtaining repeated hepatitis B PCR every 3 months during treatment and for the 12 months after last dose of study drug according to usual clinical practice in order to monitor for reactivation of hepatitis B is recommended.\n3. Estimated Glomerular Filtration Rate (Cockcroft-Gault Appendix C) ≤30 mL\u002Fmin\u002F1.73m2.\n4. Absolute neutrophil count (ANC) \\\u003C 1.0 X 109\u002FL.\n5. Platelet count \\\u003C 75 X 109\u002FL, except for patients with bone marrow involvement by CLL in which case the platelet count must be ≥ 30 X 109\u002FL.\n6. Serum aspartate aminotransferase (AST)\u002Fserum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)\u002Fserum glutamate pyruvate transaminase (SGPT) \\>2.5 x upper limit of normal (ULN).\n7. Serum total bilirubin \\> 1.5 x ULN, except in cases of Gilbert's syndrome.\n8. Prothrombin time\u002FINR or aPTT (in the absence of Lupus anticoagulant) \\> 2x ULN.\n9. Active bleeding, history of bleeding diathesis (eg, haemophilia or von Willebrand disease).\n10. Unable to swallow capsules, or has disease significantly affecting gastrointestinal function that would limit absorption of oral medication.\n11. Currently active, clinically significant cardiovascular disease or a history of myocardial infarction within 3 months prior to enrollment. Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening can enrol on study.\n12. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study drug.\n13. Systemic infection that has not resolved prior to initiating study treatment in spite of adequate anti-infective therapy.\n14. Pregnant or lactating females.\n15. Participation in any clinical study or having taken any investigational therapy within 28 days prior to initiating study therapy.\n16. Central nervous system (CNS) involvement as documented by spinal fluid cytology or imaging.\n17. Prior history of malignancies, other than CLL, unless the patient has been free of the disease for ≥ 3 years.\n\n    Exceptions include the following:\n    * Basal cell carcinoma of the skin\n    * Squamous cell carcinoma of the skin\n    * Carcinoma in situ of the cervix\n    * Carcinoma in situ of the breast\n    * Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)\n18. Presence of autoimmune haemolytic anaemia or autoimmune thrombocytopenia.\n19. Major surgery within the last 28 days prior to registration.\n20. History of stroke or intracranial haemorrhage within 6 months prior to enrollment.\n21. Requires treatment with strong CYP3A4\u002F5 Inhibitors.\n22. Known history of drug-specific hypersensitivity or anaphylaxis to study drug (including active product or excipient components).\n23. Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of zanubrutinib, or put the study outcomes at undue risk.",{"count":152,"type":21},106,[51],"The goal of this phase II randomized open label study is to compare the rate of complete remission (CR) with undetectable minimal residual disease (uMRD) obtained with zanubrutinib in combination with obinutuzumab with two different schedules of administration of obinutuzumab (starting obinutuzumab at cycle 2 or 12 months) in patients with previously untreated Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). There is scarce information about which is the most appropriate schedule of combining the BTKi and the anti-CD20 monoclonal antibody, and whether treatment can be safely stopped in those patients attaining deep responses (CR with uMRD) remains to be determined.\n\nResponse will be assessed after 20 cycles of treatment for the primary objective of the study. Patients attaining uMRD will stop treatment with zanubrutinib, whereas the rest of patients will continue on treatment with zanubrutinib until progression, unacceptable toxicity, or trial completion, whichever comes first.",[27,28],[157,158,159],"zanubrutinib","obinutuzumab","untreated CLL\u002FSLL","2026-06-23",{"date":133,"type":33},{"date":163,"type":33},"2024-09-02",{"date":165,"type":21},"2032-05-31",{"name":167,"class":63},"PETHEMA Foundation",19,{"id":170,"slug":171,"hasResults":12,"nctId":172,"briefTitle":173,"officialTitle":174,"acronym":4,"eligibilityCriteria":175,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":176,"enrollmentInfo":177,"targetDuration":4,"studyType":22,"phases":179,"briefSummary":181,"conditions":182,"keywords":189,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":160,"lastUpdatePostDateStruct":196,"startDateStruct":198,"completionDateStruct":200,"leadSponsor":202,"locationsCount":64},"100544095","phase-1-anti-cd19-chimeric-antigen-receptor-t-cell-immunotherapy-for-leukemias-100544095","NCT06364423","Anti-CD19 Chimeric Antigen Receptor T-Cell Immunotherapy for Leukemias","Phase I\u002FII Trial of Anti-CD19 Chimeric Antigen Receptor T-Cell Immunotherapy for B-cell Leukemias","* INCLUSION CRITERIA:\n* Malignancy criteria\n\n  * Histologically confirmed participants with either CLL or SLL or B-cell acute lymphoblastic leukemia or lymphoma (ALL) via immunohistochemical or flow cytometry methods will be eligible. Participants with evidence of Richter s transformation of CLL\u002FSLL are also eligible. Participants with Richter s transformation must have current or prior evidence of CLL, confirmed by review of a current or prior histological sample by NIH pathologists or confirmed by flow cytometry performed at the NIH.\n  * Demonstration of CD19 expression on CLL\u002FSLL or ALL, as assessed by the NCI Laboratory of Pathology or NIH Department of Laboratory Medicine Hematopathology section. For participants with pathologically confirmed Richter s transformation, the transformed cells must also have CD19 expression.\n  * CD19 expression must be uniform meaning no populations of clearly CD19-negative CLL\u002FSLL, Richter s or ALL cells are observed.\n  * CD20 must be detected on \\>= 20% of malignant cells by flow cytometry or immunohistochemistry. Documentation of CD20 expression is not required for patients who have received CD20-directed therapy within 90 days prior to the date of enrollment.\n  * The last dosage of systemic therapy (including corticosteroids) must be at least 14 days prior to the first dose of rituximab, with the exceptions of BTK inhibitors (BTKi) for CLL\u002FSLL and tyrosine kinase inhibitors (TKI) for ALL. Participants who were receiving a BTKi for CLL\u002FSLL or a TKI for ALL for at least 14 days prior to protocol enrollment can continue these agents during part of the time the participants are enrolled on this clinical trial.\n  * For participants who have received antibodies targeting CD19, at least sixty days must elapse between therapy with antibodies targeting CD19 and CAR T-cell infusion.\n  * Participants with CLL\u002FSLL must have received at least two prior treatment regimens, at least one of which must have contained a Bruton s tyrosine kinase (BTK) inhibitor. Participants who took a BTK inhibitor but stopped due to intolerance are potentially eligible. Participants with relapsed or refractory CLL\u002FSLL after alloHSCT are eligible.\n  * Participants with refractory ALL that failed induction or participants with relapsed ALL after a standard induction regimen or after any later line of therapy are eligibleParticipants with relapsed or refractory ALL after alloHSCT are eligible.\n  * All participants must have measurable malignancy as defined by at least one of the criteria below.\n\n    * Presence of CLL,SLL, or ALL masses that are measurable (minimum 1.5 cm in largest diameter) by CT scan or PET\u002FCT is required unless bone marrow or blood involvement with malignancy is detected.\n    * For CLL\u002FSLL or ALL with only bone marrow and\u002For blood involvement, no mass is necessary, but if a mass is not present, bone marrow and\u002For blood malignancy must be detectable by flow cytometry. Any level of CLL\u002FSLL or ALL detectable by flow cytometry is sufficient.\n* Other inclusion criteria:\n\n  * Age \\>= 18 years.\n  * Performance status (ECOG) 0-1.\n  * Participants must have adequate organ and marrow function as defined below:\n\n    * ANC \\>= 1,000\u002FmcL without the support of filgrastim or other growth factors in the 10 days prior to screening assessment\n    * platelets \\>= 50,000\u002FmcL without transfusion support\n    * hemoglobin \\>= 8 g\u002FdL\n    * total bilirubin \\\u003C= 2.0 mg\u002FdL\n    * ALT or AST Serum ALT and AST less or equal to 3 times the upper limit of the institutional normal unless liver involvement by malignancy is demonstrated. If liver involvement with malignancy is detected, ALT and AST must be less than or equal to 5 times the upper limit of normal\n    * Serum Creatinine Serum creatinine levels \\\u003C 1.5 X institutional ULN. Participants with serum creatinine \\>= 1.5 X institutional ULN may participate if serum creatinine eGFR is \\>=50 mL\u002Fmin\u002F1.73m\\^2 by 2021 CKD-EPI equation.\n\n      * ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase);\n      * AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.\n      * (A)Creatinine clearance (CrCl) or eGFR should be calculated per institutional standard.\n  * For CLL participants, B cells must make up less than 95% of blood lymphocytes on a lymphocyte phenotyping profile TBNK at the time of screening assessment. For ALL participants, the peripheral blood blast percentage on CBC differential must be 1% or less.\n  * Room air oxygen saturation of 92% or greater\n  * Participants of child-bearing or child-fathering potential must be willing to practice abstinence or highly effective contraception starting at the time of study entry, for the duration of study therapy, and for 12 months after receiving the protocol treatment.\n  * Participants must agree not to donate eggs for 12 months after receiving the protocol treatment\n  * Participants who are breastfeeding must be willing to cease breastfeeding from study treatment initiation through 12 months after the last dose of the study drugs.\n  * Participants must have a negative blood PCR test for hepatitis B DNA. If hepatitis B DNA (PCR) testing is not available, participants must have a negative hepatitis B surface antigen and negative hepatitis B core antibody test.\n  * Participants must have a negative blood PCR test for hepatitis C RNA. Only if Hepatitis C PCR testing is not available in a timely manner, participants must have a negative Hepatitis C antibody test.\n  * Cardiac ejection fraction of greater than or equal to 50% by echocardiography and no evidence of hemodynamically significant pericardial effusion as determined by an echocardiogram within 30 days prior to treatment start.\n  * All participants must have the ability to understand and willingness to sign a written informed consent.\n  * All participants must be willing to undergo mandatory biopsies during the study.\n\nEXCLUSION CRITERIA:\n\n* Participants who are receiving any other investigational agents.\n* Participants who have had prior CAR T-cell therapy.\n* Participants who have had a live-attenuated or viral vector-based vaccine in the last 60 days prior to pre-leukapheresis rituximab. Participants who plan to receive a live attenuated or viral vector-based vaccine within the first 100 days after CAR T-cell infusion.\n* Participants that require urgent therapy due to tumor mass effects or spinal cord compression.\n* Current\u002Factive HIV infection, as measured by seropositivity for HIV antibody.\n* Participants with second malignancies in addition to their CLL or ALL are not eligible if the second malignancy has required treatment with surgery, radiation or chemotherapy, or other therapies within the past 2 years or is not in complete remission. Exceptions are that, in the last 2 years, participants may have had successful resection of non-metastatic basal cell or squamous cell carcinoma of the skin, and participants may have received hormonal therapy for fully resected breast cancer.\n* Positive beta Human chorionic gonadotropin (Beta-HCG) serum or urine pregnancy test in women of childbearing potential (WOCBP) performed at screening.\n* Active uncontrolled systemic infections (defined as infections causing fevers within 48 hours of the date of planned protocol rituximab or chemotherapy start and infections requiring intravenous antibiotics when intravenous antibiotics have been administered for less than 72 hours at the time of protocol rituximab or chemotherapy start). There must be objective evidence of infection, including, but not limited to, a positive blood, urine or sputum culture, positive nasal swab or blood test for viral infection, or the appearance of infiltrates on imaging of the lung.\n* Active coagulation disorders, major uncontrolled medical illnesses of the cardiovascular, respiratory, endocrine, renal, gastrointestinal, genitourinary or immune system, history of myocardial infarction, history of ventricular tachycardia or ventricular fibrillation, active cardiac arrhythmias with the exception of atrial fibrillation with baseline heart rates less than or equal to 90 beats per minute, (Use of medications to control heart rate is allowed.), active obstructive or restrictive pulmonary disease, or active autoimmune diseases such as rheumatoid arthritis. These include uncontrolled intercurrent illness manifesting as electrolyte derangements or as assessed by chemistries.\n* Significant neurologic disorders, including a history of a seizure disorder as an adult, that are not completely and permanently resolved and not requiring current treatment.\n* Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease) that has not been cured by a prior allogeneic stem cell transplant.\n* For participants that have not had prior allogeneic stem cell transplant: Systemic corticosteroid steroid therapy of any dose greater than 5 mg\u002Fday or more of prednisone or equivalent is not allowed within 14 days prior to the first dose of rituximab. Corticosteroid creams, ointments, and eye drops are allowed.\n* For participants that have had prior allogeneic stem cell transplant: Receiving any systemic immunosuppressive drugs including corticosteroids at doses of greater than 5 mg\u002Fday prednisone or equivalent within 28 days prior to Rituximab. Topical corticosteroid preparations applied to the skin such as solutions, creams, and ointments are allowed. Inhaled corticosteroids are allowed, and corticosteroid eye drops are allowed.\n* History of severe immediate hypersensitivity reaction to any of the agents used in this study, including hypersensitivity to aminoglycoside antibiotics, which may be used in the cell culture media.\n* Participants with CNS3 disease, neurologic signs of CNS disease, radiologically detected active CNS lymphoma or meningeal involvement.\n* Checkpoint inhibitor drugs such as pembrolizumab or nivolumab or other antibodies targeting PD-1 or PDL-1 within 180 days of pre-leukapheresis rituximab. This is because of possible effects checkpoint inhibitor therapy could have on the participant's T cells.\n* Known active alcohol or drug abuse.\n* History of allergy to study drug components.\n* Active tumor lysis syndrome as assessed by serum uric acid, LDH, calcium, and phosphorus.\n* Active rhabdomyolysis as assessed by elevated CK and acute change in renal function as reflected by increased creatinine and blood urea nitrogen (BUN).\n* Active diabetic ketoacidosis or hyperosmolar hyperglycemic state, as assessed by serum glucose. The urine will be tested for ketones if serum glucose is over 350 mg\u002FdL at screening.\n* Participants who received a previous allogeneic HSCT must have no (grade 0) acute GVHD (Appendix H) and either no chronic GVHD or mild chronic GVHD. Participants with GVHD meeting the above criteria with local therapy (topical cutaneous steroids, inhaled steroids, and eye drops) will be eligible for enrollment.","120 Years",{"count":178,"type":21},132,[180,51],"PHASE1","Background:\n\nChronic lymphocytic leukemia (CLL),small lymphocytic lymphoma (SLL) and B-cell acute lymphoblastic leukemia or lymphoma (ALL) are blood cancers that affect certain white blood cells. Advanced forms of these diseases are difficult to treat. CD19 is a protein often found on the surfaces of these cancer cells. Researchers can modify a person's own immune cells (T cells) to target CD19. When these modified T cells are returned to the body-a treatment called anti-CD19 chimeric antigen receptor (CAR) T cell therapy-they may help kill cancer cells.\n\nObjective:\n\nTo test anti-CD19 CAR T cell therapy in people with CLL or SLL and ALL.\n\nEligibility:\n\nPeople aged 18 years and older with CLL or SLL and ALL that has not been controlled with standard drugs.\n\nDesign:\n\nParticipants will be screened. They will have imaging scans and tests of their heart function. If a sample of tissue from their tumor is not available, a new one may be taken; the sample will be tested for CD19.\n\nParticipants will receive a drug to reduce the leukemia cells in their blood. Then they will undergo apheresis: Blood will be taken from the body through a needle. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a different needle. The collected T cells will be gene edited to make them attack cells with CD19.\n\nParticipants will take drugs to prepare them for treatment for 3 days. These drugs will start 5 days before the treatment. Then their own modified CAR T cells will be returned to their bloodstream. Participants will stay in the hospital for at least 9 days after the treatment.\n\nFollow-up visits will continue for 5 years.",[183,184,185,186,187,188,28],"Leukemia, Lymphocytic, Chronic, B-Cell","B-Lymphocytic Leukemia, Chronic","B-Cell Chronic Lymphocytic Leukemia","Acute Lymphoblastic Leukemia","Lymphoblastic Lymphoma","Leukemia, Acute Lymphoblastic",[28,190,191,27,192,193,194,195,17,186],"Immunotherapy","CLL","Chimeric Antigen Receptors","Autologous T Cells Infusion","Adoptive T Cell Therapy","CAR",{"date":197,"type":33},"2026-06-24",{"date":199,"type":33},"2024-09-03",{"date":201,"type":21},"2030-07-01",{"name":39,"class":40},{"id":204,"slug":205,"hasResults":12,"nctId":206,"briefTitle":207,"officialTitle":208,"acronym":4,"eligibilityCriteria":209,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":210,"targetDuration":4,"studyType":22,"phases":212,"briefSummary":213,"conditions":214,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":160,"lastUpdatePostDateStruct":215,"startDateStruct":216,"completionDateStruct":218,"leadSponsor":220,"locationsCount":222},"100325407","phase-2-acalabrutinib-with-or-without-obinutuzumab-in-treating-patients-with-early-stage-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma-100325407","NCT03516617","Acalabrutinib With or Without Obinutuzumab in Treating Patients With Early-Stage Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma","Randomized Phase 2 Study Comparing Acalabrutinib to Acalabrutinib and Obinutuzumab in the Treatment of Patients With Early-Stage Chronic Lymphocytic Leukemia\u002FSmall Lymphocytic Lymphoma (CLL\u002FSLL) Who Are at High Risk of Disease Progression","Inclusion Criteria:\n\n* Age \\>= 18 years\n* Diagnosis of:\n\n  * Biopsy-proven small lymphocytic lymphoma (SLL) , or\n  * Diagnosis of chronic lymphocytic leukemia (CLL) with a clonal B-cell population in the peripheral blood with immunophenotyping consistent with CLL as follows:\n\n    * The population of lymphocytes share both B-cell antigens (CD19, CD20 \\[typically dim expression\\], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.)\n    * Clonality as evidenced by kappa or lambda light chain expression (typically dim immunoglobulin expression) or other genetic method (e.g. IGHV analysis)\n    * Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative fluorescence in situ hybridization (FISH) analysis for t(11;14)(IgH\u002FCCND1)\n* Patients must be previously untreated\n\n  * Note: Prior chemotherapy or monoclonal antibody based therapy for treatment of CLL or SLL will be considered prior therapy; nutraceutical treatments with no established benefit in CLL (such as epigallocatechin gallate or EGCG, found in green tea or other herbal treatments or supplemental vitamins) will not be considered \"prior treatment\"; prior corticosteroid therapy for an indication other than CLL\u002FSLL will not be considered \"prior treatment\"\n* All patients will undergo testing for prognostic factors according to the CLL-IPI (testing obtained =\\\u003C 730 days prior to registration)\n\n  * Note: If the results for any of the prognostic factors included in the CLL-IPI are unknown including IGVH mutation status results not being available due to a failed laboratory assay, the patient is not eligible\n  * Note: When determining CLL-IPI, use most recent test results, if more than one result is available\n  * Note: Patients with CLL-IPI risk category of high risk or very high risk (total score of 4-10) will be randomized to Arms A or B\n  * Note: Patients with CLL-IPI risk category of low risk or intermediate risk (total score of 0-3) will be registered to Arm C\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2\n* Provide written informed consent\n* Willing to provide blood and saliva samples for correlative research purposes\n* Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)\n* For high risk and very high risk CLL-IPI (Arms A and B) only: Absolute neutrophil count (ANC) \\>= 1500\u002Fmm\\^3 (obtained =\\\u003C 30 days prior to randomization)\n* For high risk and very high risk CLL-IPI (Arms A and B) only: Platelet count \\>= 100,000\u002Fmm\\^3 (obtained =\\\u003C 30 days prior to randomization)\n* For high risk and very high risk CLL-IPI (Arms A and B) only: Hemoglobin \\>= 11.0 g\u002FdL (obtained =\\\u003C 30 days prior to randomization)\n* For high risk and very high risk CLL-IPI (Arms A and B) only: Aspartate aminotransferase (aspartate transaminase \\[AST\\]) =\\\u003C 3 x upper limit of normal (ULN) (obtained =\\\u003C 30 days prior to randomization)\n* For high risk and very high risk CLL-IPI (Arms A and B) only: Creatinine =\\\u003C 1.5 X ULN (obtained =\\\u003C 30 days prior to randomization)\n* For high risk and very high risk CLL-IPI (Arms A and B) only: Total bilirubin =\\\u003C 1.5 x upper limit of normal (ULN) (or total bilirubin =\\\u003C 3.0 x ULN with direct bilirubin =\\\u003C 1.5 x ULN in patients with well-documented Gilbert's syndrome (obtained =\\\u003C 30 days prior to randomization)\n* For high risk and very high risk CLL-IPI (Arms A and B) only: Prothrombin time (PT), international normalized ratio (INR), and partial thromboplastin time (PTT) =\\\u003C 1.5 X ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of coagulants (obtained =\\\u003C 30 days prior to randomization)\n* Negative serum pregnancy test done =\\\u003C 7 days prior to registration, for persons of childbearing potential only\n* Will provide bone marrow aspirate sample for correlative research purposes\n\nExclusion Criteria:\n\n* Date of CLL\u002FSLL diagnosis \\>= 24 months prior to registration\n* Prior exposure to ibrutinib or to a BCR inhibitor (e.g. Btk or PI3 kinase or Syk inhibitors) or a BCL-2 inhibitor (e.g. venetoclax)\n* Known central nervous system (CNS) lymphoma or leukemia\n* Patients with any of the following indications for chemotherapy:\n\n  * Evidence of progressive marrow failure as manifested by the development of or worsening anemia (=\\\u003C 11 g\u002FdL) and\u002For thrombocytopenia (=\\\u003C 100 x 10\\^9\u002FL) not due to autoimmune disease\n  * Symptomatic or progressive lymphadenopathy, splenomegaly or hepatomegaly\n  * One or more of the following disease-related symptoms:\n\n    * Weight loss \\>= 10% within the previous 6 months\n    * Extreme fatigue attributed to CLL\n    * Fevers \\>= 100.4 degrees Fahrenheit (F) for 2 weeks without evidence of infection\n    * Drenching night sweats without evidence of infection\n* Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens\n* Patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm\n* Other active malignancy =\\\u003C 2 years prior to registration; EXCEPTIONS: Non-melanotic skin cancer, carcinoma-in-situ of the cervix, or early stage prostate cancer\n* History of myocardial infarction =\\\u003C 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias\n* For high risk and very high risk CLL-IPI (Arms A and B) only:\n\n  * Any of the following:\n\n    * Pregnant persons\n    * Nursing persons\n    * Persons of childbearing potential who are unwilling to employ highly effective contraception\n  * Serologic status reflecting active hepatitis B or C infection\n\n    * NOTE: Subjects with hepatitis B core antibody positive who are surface antigen negative or who are hepatitis C antibody positive will need to have a negative polymerase chain reaction (PCR) result before randomization; those who are hepatitis B surface antigen positive or hepatitis B PCR positive and those who are hepatitis C PCR positive will be excluded\n  * History of stroke or intracranial hemorrhage within 6 months before randomization\n  * History of bleeding diathesis (e.g. hemophilia, von Willebrand disease)\n  * Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon) within 7 days of first dose of study drug and while on study\n  * Requires treatment with a strong CYP3A inducer\n  * Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening\n  * History of confirmed progressive multifocal leukoencephalopathy (PML)\n  * Received a vaccination with a live vaccine =\\\u003C 28 days prior to randomization",{"count":211,"type":21},120,[51],"This phase II trials studies how well acalabrutinib with or without obinutuzumab works in treating patients with early-stage chronic lymphocytic leukemia or small lymphocytic lymphoma. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving acalabrutinib with or without obinutuzumab will work better in treating patients with early-stage chronic lymphocytic leukemia or small lymphocytic lymphoma.",[27,28],{"date":197,"type":33},{"date":217,"type":33},"2018-09-10",{"date":219,"type":21},"2030-10-16",{"name":221,"class":63},"Mayo Clinic",3,{"id":224,"slug":225,"hasResults":12,"nctId":226,"briefTitle":227,"officialTitle":228,"acronym":4,"eligibilityCriteria":229,"healthyVolunteers":12,"sex":17,"minAge":4,"maxAge":230,"enrollmentInfo":231,"targetDuration":4,"studyType":22,"phases":233,"briefSummary":234,"conditions":235,"keywords":257,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":160,"lastUpdatePostDateStruct":263,"startDateStruct":264,"completionDateStruct":266,"leadSponsor":268,"locationsCount":64},"100309946","phase-2-myeloablative-allo-hsct-with-related-or-unrelated-donor-for-heme-disorders-100309946","NCT03314974","Myeloablative Allo HSCT With Related or Unrelated Donor for Heme Disorders","Myeloablative Allogeneic Hematopoietic Cell Transplantation Using a Related or Unrelated Donor for the Treatment of Hematological Diseases","-Inclusion Criteria:\n\n* Age: ≤ 60 years of age\n* Performance Status: Karnofsky ≥ 70%, Lansky play score ≥ 70\n* Consent: Voluntary written consent (adult or legally authorized representative; or parental\u002Fguardian)\n* Adequate Organ Function:\n\n  * Renal: Creatinine \\\u003C2x upper limit of normal. Patients above this limit must have creatinine clearance ≥ 40 ml\u002Fmin\u002F1.73m2 as determined by an age-appropriate method, such as cystatin C GFR.\n  * Hepatic: Bilirubin, AST, alkaline phosphatase \\\u003C4 times the upper limit of institutional normal\n  * Pulmonary: Diffusion capacity of oxygen, corrected for hemoglobin, \\> 50% of predicted. For pediatric patients not able to undergo PFTs or diffusion testing: O2 sat of \\>95% on room air\n  * Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction \\> 45%. For children not able to cooperate with MUGA or echocardiography, such should be clearly stated in the physician's documentation\n  * HIV Status: HIV infection with undetectable viral load. All HIV+ patients must be evaluated by Infectious Disease (ID) and a HIV management plan establish prior to transplantation\n\nOther Inclusion Criteria:\n\n* Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment.\n* Donor Availability: Patients considered for transplantation must have a sufficient graft as based on current criteria of the University of Minnesota Blood and Marrow Transplantation Program\n* Eligible Diseases and Status: Patients are eligible unless their treatment is to be guided by a higher priority protocol.\n* Acute Leukemias: Must be in remission by morphology (≤5% blasts). Also a small percentage of blasts that is equivocal between marrow regeneration vs. early relapse are acceptable provided there are no associated cytogenetic markers consistent with relapse.\n* Acute Myeloid Leukemia (AML) and related precursor neoplasms: 2nd or greater complete remission (CR); first complete remission (CR1) in patients \\> 60 years old; CR1 in ≤ 60 years old that is NOT considered as favorable-risk.\n* Favorable risk AML is defined as having one of the following:\n\n  * t(8,21) without cKIT mutation\n  * inv(16) or t(16;16) without cKIT mutation\n  * Normal karyotype with mutated NPM1 and wild type FLT-ITD\n  * Normal karyotype with double mutated CEBPA\n  * Acute prolymphocytic leukemia (APL) in first molecular remission at the end of consolidation\n* Very high risk pediatric patients with AML: Patients \\\u003C21 years, however, are eligible with (M2 marrow) with \\\u003C 25% blasts in marrow after having failed one or more cycles of chemotherapy.\n* Acute lymphoblastic leukemia (ALL)\u002Flymphoma: second or greater CR; CR1 unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities; CR1 high-risk ALL.\n* High risk ALL is defined as having one of the following:\n\n  * Evidence of high risk cytogenetics, e.g. t(9;22), t(1;19), t(4;11), other MLL rearrangements, IKZF1\n  * 30 years of age or older at diagnosis\n  * White blood cell counts of greater than 30,000\u002FmcL (B-ALL) or greater than 100,000\u002FmcL (T-ALL) at diagnosis\n  * CNS leukemia involvement during the course of disease\n  * Slow cytologic response (\\>10% lymphoblasts in bone marrow on Day 14 of induction therapy)\n  * Evidence of persistent immonophenotypic or molecular minimal residual disease (MRD) at the end of induction and consolidation therapy\n* Very high risk pediatric patients with ALL: patients \\\u003C21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction. They are eligible once they achieve a complete remission.\n* Chronic Myelogenous Leukemia excluding refractory blast crisis: To be eligible in first chronic phase (CP1) patient must have failed or be intolerant to one or more tyrosine kinase inhibitors.\n* Plasma Cell Leukemia after initial therapy, in patients who have achieved at least a partial remission\n* Myeloproliferative Neoplasms\u002FMyelofibrosis, either primary as a result of polycythemia vera or essential thrombocythemia, with disease risk of intermediate or high-risk according to DIPSS criteria. Blasts must be \\\u003C10% by bone marrow aspirate morphology.\n* Myelodysplasia (MDS) IPSS INT-2 or High Risk (i.e. RAEB, RAEBt) or Refractory Anemia with severe pancytopenia, transfusion dependence, or high risk cytogenetics or molecular features. Blasts must be \\\u003C 10% by a representative bone marrow aspirate morphology.\n* Chronic Lymphocytic Leukemia\u002FSmall Lymphocytic Lymphoma (CLL\u002FSLL), Marginal Zone B-Cell Lymphoma or Follicular Lymphoma are eligible if there was disease progression\u002Frelapse within 12 of achieving a partial or complete remission. Patients who had remissions lasting \\> 12 months, are eligible after at least two prior therapies. Patients with bulky disease (nodal mass greater than 5 cm) should be considered for debulking chemotherapy before transplant.\n* Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia are eligible after initial therapy in CR1+ or PR1+.\n* Diffuse large Cell NHL \\> CR\u002F\\> PR: Patients in CR\u002FPR with initial short remission (\\\u003C6 months) are eligible, or those who have failed\u002For are not eligible for autologous transplant.\n* Lymphoblastic Lymphoma, Burkitt's Lymphoma, and other high-grade NHL after initial therapy if stage III\u002FIV in CR1\u002FPR1 or after progression if stage I\u002FII \\\u003C 1 year.\n* Multiple Myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or β-2 microglobulin \\> 3 mg\u002FL, may be considered for this protocol after initial therapy.\n* Juvenile myelomonocytic leukemia\n* Biphenotypic\u002FUndifferentiated\u002FProlymphocytic Leukemias in first or subsequent CR.\n* MRD positive leukemia (AML, ALL or accelerated\u002Fblast phase CML). Selected patients in morphologic CR, but with positive immunophenotypic (flow cytometry) or molecular evidence of MRD may be eligible if recent chemotherapy has not resulted in MRD negative status.\n* Natural Killer Cell Malignancies\n* Acquired Bone Marrow Failure Syndromes except for Fanconi Anemia or Dyskeratosis Congenita\n* Other Leukemia Subtypes: A major effort in the field of hematology is to identify patients who are of high risk for treatment failure so that patients can be appropriately stratified to either more (or less) intensive therapy. This effort is continually ongoing and retrospective studies identify new disease features or characteristics that are associated with treatment outcomes. Therefore, if new features are identified after the writing of this protocol, patients can be enrolled with the approval of two members of the study committee.\n\nExclusion Criteria:\n\n* Chemotherapy refractory large cell and high grade NHL (i.e., progressive disease after \\> 2 salvage regimens)\n* CML in blast crisis\n* Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressing on salvage therapy.\n* Evidence of progressive disease by imaging modalities or biopsy - persistent PET activity, though possibly related to lymphoma, is not an exclusion criterion in the absence of CT changes indicating progression.\n* Active central nervous system malignancy\n* if ≤ 18 years old, prior myeloablative transplant within the last 6 months. If \\>18 years old prior myeloablative allotransplant or autologous transplant\n* Active HIV infection or known HIV positive serology\n* active uncontrolled infection\n* Pregnant or breastfeeding. The agents used in this study include Pregnancy Category D: known to cause harm to a fetus. Females of childbearing potential must have a negative pregnancy test prior to starting therapy.","60 Years",{"count":232,"type":21},300,[51],"This is a Phase II study of allogeneic hematopoietic stem cell transplant (HCT) using a myeloablative preparative regimen (of either total body irradiation (TBI); or, fludarabine\u002Fbusulfan for patients unable to receive further radiation). followed by a post-transplant graft-versus-host disease (GVHD) prophylaxis regimen of post-transplant cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF).",[236,237,186,78,238,239,240,241,242,243,244,27,28,245,79,81,246,247,248,187,249,250,251,252,253,254,255,256],"Acute Leukemia","Acute Myeloid Leukemia","Chronic Myelogenous Leukemia","Plasma Cell Leukemia","Myeloproliferative Neoplasms","Myelofibrosis","Myelodysplasia","Refractory Anemia","High Risk Anemia","Marginal Zone B-Cell Lymphoma","Mantle-Cell Lymphoma","Prolymphocytic Leukemia","Diffuse Large Cell Non Hodgkins Lymphoma","Burkitt Lymphoma","High Grade Non-Hodgkin's Lymphoma, Adult","Multiple Myeloma","Juvenile Myelomonocytic Leukemia","Biphenotypic\u002FUndifferentiated\u002FProlymphocytic Leukemias","MRD Positive Leukemia","Natural Killer Cell Malignancies","Acquired Bone Marrow Failure Syndromes",[258,17,259,260,191,261,262],"AML","MDS","NHL","CML","SLL",{"date":133,"type":33},{"date":265,"type":33},"2018-03-30",{"date":267,"type":21},"2028-06-10",{"name":269,"class":63},"Masonic Cancer Center, University of Minnesota",{"id":271,"slug":272,"hasResults":12,"nctId":273,"briefTitle":274,"officialTitle":275,"acronym":4,"eligibilityCriteria":276,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":277,"targetDuration":4,"studyType":22,"phases":279,"briefSummary":280,"conditions":281,"keywords":282,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":285,"lastUpdatePostDateStruct":286,"startDateStruct":288,"completionDateStruct":290,"leadSponsor":292,"locationsCount":294},"100590881","phase-3-a-study-to-evaluate-the-safety-and-efficacy-of-bgb-16673-compared-to-pirtobrutinib-in-adults-with-relapsedrefractory-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma-100590881","NCT06973187","A Study to Evaluate the Safety and Efficacy of BGB-16673 Compared to Pirtobrutinib in Adults With Relapsed\u002FRefractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma","A Phase 3, Open-Label, Randomized Study to Evaluate the Safety and Efficacy of BGB-16673 Compared to Pirtobrutinib in Patients With Relapsed\u002FRefractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma","Inclusion Criteria:\n\n* Confirmed diagnosis of CLL or SLL, requiring treatment, based on 2018 iwCLL criteria\n* Previously received treatment for CLL\u002FSLL with a covalent Bruton tyrosine kinase inhibitor (cBTKi). Patients should have disease relapsed after or refractory to at least 1 line of therapy including a cBTKi.\n* Participants with SLL must have measurable disease by computed tomography\u002Fmagnetic resonance imaging, defined as ≥ 1 lymph node \\> 1.5 cm in longest diameter and measurable in 2 perpendicular diameters.\n\nExclusion Criteria:\n\n* Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation.\n* History of known bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention\n* History of ischemic stroke or intracranial hemorrhage within 6 months before first dose of study drug\n* Prior exposure to any Bruton tyrosine kinase (BTK) protein degraders or noncovalent Bruton tyrosine kinase inhibitor (ncBTKi).\n* Current or history of central nervous system involvement including the brain, spinal cord, leptomeninges, and cerebrospinal fluid (as documented by imaging, cytology, or biopsy) by CLL\u002FSLL\n\nNOTE: Other protocol defined Inclusion\u002FExclusion criteria may apply.",{"count":278,"type":21},500,[24],"The purpose of this study is to evaluate the efficacy and safety of BGB-16673 alone compared with pirtobrutinib in patients with relapsed or refractory (R\u002FR) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had been previously treated with a covalent Bruton tyrosine kinase inhibitor (cBTKi).",[27,28],[283,284],"Noncovalent Bruton tyrosine kinase inhibitor","Bruton tyrosine kinase-targeted protein degrader","2026-06-17",{"date":287,"type":33},"2026-06-18",{"date":289,"type":33},"2025-09-04",{"date":291,"type":21},"2028-04-17",{"name":293,"class":142},"BeOne Medicines",167,{"id":296,"slug":297,"hasResults":12,"nctId":298,"briefTitle":299,"officialTitle":300,"acronym":301,"eligibilityCriteria":302,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":303,"targetDuration":4,"studyType":22,"phases":305,"briefSummary":306,"conditions":307,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":285,"lastUpdatePostDateStruct":313,"startDateStruct":314,"completionDateStruct":316,"leadSponsor":318,"locationsCount":319},"100439778","phase-1-a-dose-escalation-and-expansion-study-of-bgb-16673-in-participants-with-b-cell-malignancies-100439778","NCT05006716","A Dose-Escalation and Expansion Study of BGB-16673 in Participants With B-Cell Malignancies","A Phase 1\u002F2, Open-Label, Dose-Escalation and -Expansion Study of the Bruton Tyrosine Kinase Targeted Protein Degrader BGB-16673 in Patients With B-Cell Malignancies","CaDAnCe-101","Inclusion Criteria :\n\n1. Confirmed diagnosis (per World Health Organization (WHO) guidelines, unless otherwise noted) of one of the following: Marginal Zone Lymphoma (MZL), R\u002FR follicular lymphoma (FL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL\u002FSLL), Waldenström macroglobulinemia (WM), R\u002FR diffuse large B-cell lymphoma (DLBCL), or Richter's transformation to DLBCL.\n2. Participants who have previously received a covalently-binding Bruton´s tyrosine kinase (BTK) inhibitor (BTKi) in any line of therapy must have received treatment with the BTK inhibitor for ≥ 8 weeks (unless reason for discontinuation is intolerance).\n3. For dose-finding and dose-expansion, participants who had previously received a covalently-binding BTK inhibitor as monotherapy or in combination with other anticancer agents are eligible for the study if they meet any of the following criteria: discontinued the previous BTK inhibitor due to disease progression, experienced disease progression after completing treatment with a BTK inhibitor or discontinued the BTK inhibitor due to toxicity or intolerance.\n4. Phase 2 Cohorts in R\u002FR CLL\u002FSLL, R\u002FR MCL, and R\u002FR WM only: Participants who previously received a BTKi are eligible if they had disease progression on only one regimen containing a covalent BTKi. Note: Participants may have received treatment with ≥ 2 different covalent BTKis if additional BTKis were discontinued secondary to an event other than disease progression.\n5. Measurable disease by radiographic assessment or serum IgM level (WM only)\n6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2\n7. Participants enrolling in the dose finding phase of the study may be previously treated with a BTKi or may be naïve to BTKi therapy depending on the diagnosis and country of enrollment; participants with MCL enrolling in the expansion cohorts (Phase 2) must have been treated with a BTKi in a prior line of therapy; CLL\u002FSLL participants, in addition to being treated with a BTKi in a prior line of therapy, must also have received a Bcl-2 inhibitor in a prior line of therapy as well (Phase 2).\n\nExclusion Criteria:\n\n1. Prior malignancy (other than the disease under study) within the past 2 years, except in situ malignancies that have been curatively resected, localized breast cancer treated with curative intent with no evidence of breast active disease for more than 3 years and receiving adjuvant hormonal therapy, localized Gleason score ≤ 6 prostate cancer undergoing observation or treatment with androgen depravation, or any other cancer treated with curative intent, not on adjuvant treatment, and in the opinion of the investigator is unlikely to recur.\n2. Requires ongoing systemic treatment for any other malignancy\n3. Requires ongoing systemic (defined as ≥ 10 mg\u002Fday of prednisone or equivalent) corticosteroid treatment.\n4. Current or history of central nervous system involvement including the brain, spinal cord, leptomeninges, and cerebrospinal fluid (as documented by imaging, cytology, or biopsy) by B-cell malignancy, regardless of whether participants had received treatment for central nervous system disease\n5. Known active plasma cell neoplasm, prolymphocytic leukemia, T-cell lymphoma, Burkitt lymphoma, acquired immunodeficiency syndrome (AIDS)-related B-cell lymphoma, Castleman disease, post-transplant lymphoproliferative disorders, hairy cell leukemia, germinal center B-cell (GCB), DLBCL, EBV+ DLBCL NOS, primary DLBCL of the central nervous system (CNS), primary cutaneous DLBCL - leg type, DLBCL associated with chronic inflammation, primary mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, ALK+ large B-cell lymphoma, primary effusion lymphoma, high-grade B-cell lymphoma with MYC and BCL2 and\u002For BCL6 rearrangements, high-grade B-cell lymphoma - NOS, B-cell lymphoma unclassifiable with features intermediate between DLBCL and classical Hodgkin lymphoma, or history of or currently suspected transformation of an indolent lymphoma to an aggressive histology (except for participants with Richter Transformation to DLBCL are eligible for Part 1a, 1c, or Phase 2 and participants with history of follicular lymphoma transforming to non-GCB DLBCL who are eligible for Part 1a, 1c, or Phase 2).\n\nNote: Other protocol defined Inclusion\u002FExclusion criteria may apply.",{"count":304,"type":21},645,[180,51],"Study consists of two main parts to explore BGB-16673 recommended dosing, a Phase 1 monotherapy dose finding comprised of monotherapy dose escalation and monotherapy safety expansion of selected doses, and a Phase 2 (expansion cohorts)",[308,80,79,309,310,27,28,311,312],"B-cell Malignancy","Non-Hodgkin Lymphoma","Waldenström Macroglobulinemia","Mantle Cell Lymphoma","Diffuse Large B Cell Lymphoma",{"date":287,"type":33},{"date":315,"type":33},"2021-09-13",{"date":317,"type":21},"2029-11",{"name":293,"class":142},127,{"id":321,"slug":322,"hasResults":12,"nctId":323,"briefTitle":324,"officialTitle":325,"acronym":4,"eligibilityCriteria":326,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":327,"targetDuration":4,"studyType":22,"phases":329,"briefSummary":330,"conditions":331,"keywords":335,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":285,"lastUpdatePostDateStruct":337,"startDateStruct":339,"completionDateStruct":341,"leadSponsor":343,"locationsCount":64},"100404393","phase-1-anti-cd19-chimeric-antigen-receptor-t-cells-for-treatment-of-relapsed-or-refractory-non-hodgkin-lymphoma-100404393","NCT04545762","Anti-CD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma","A Phase 1 Clinical Trial of Anti-CD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma","THE DOSE ESCALATION COHORT IS CLOSED TO FURTHER ENROLLMENT.\n\nInclusion Criteria:\n\nDose expansion Cohorts:\n\nCohort B (Burkitt):\n\n1. Participants must have a diagnosis of relapsed or refractory Burkitt Lymphoma\n\n   * Participants with Burkitt lymphoma must have relapsed or failed to respond to at least 1 prior line of multiagent chemoimmunotherapy with prior exposure to both an anti-CD20 antibody agent and an anthracycline.\n   * No significant circulating disease, defined as an elevated total lymphocyte count above the upper limit of normal (ULN) due to the presence of malignant cells.\n2. Participants must have measurable disease as defined below:\n\n   * Participants with Burkitt Lymphoma must have Positron Emission Tomography (PET)-positive disease according to \"Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification\"\n\nCohort M\u002FW (Marginal\u002FWaldenström):\n\n1. Participants must have a diagnosis of relapsed or refractory Marginal Zone Lymphoma (MZL), or Lymphoplasmacytic Lymphoma (LPL)\u002FWaldenström Macroglobulinemia (WM):\n\n   o Participants with indolent lymphomas (nodal or extranodal marginal zone lymphoma, and lymphoplasmacytic lymphoma) must have relapsed after or have been refractory to ≥ 2 prior lines of multi-agent chemoimmunotherapy including prior exposure to an anti-CD20 antibody and an alkylating agent.\n2. Participants must have measurable disease as defined below:\n\n   o Participants with Marginal Zone Lymphoma or Lymphoplasmacytic Lymphoma\u002FWaldenström Macroglobulinemia: must either have PET-positive disease according to \"Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification\" or serum monoclonal immunoglobulin M (IgM) paraprotein \\> 0.5 g\u002FdL.\n3. Participants with indolent lymphoma (Marginal Zone Lymphoma or Lymphoplasmacytic Lymphoma\u002FWaldenström Macroglobulinemia) must have symptomatic disease or steady progression necessitating systemic treatment per investigator discretion.\n\nIn addition, all participants must meet the following criteria:\n\n1. CD19-positive by either immunohistochemistry or flow cytometry analysis on any biopsy. If prior anti-CD19 therapy has been administered, CD19-positivity has to be re-established on the most recent biopsy.\n2. Age ≥18 years at the time of consent.\n3. Absolute lymphocyte count \\> 100\u002FUL.\n4. Eastern Cooperative Oncology Group (ECOG) performance status \\\u003C 2.\n5. Adequate organ function, defined as:\n\n   1. Adequate bone marrow function for apheresis and lymphodepleting chemotherapy\n   2. Hemoglobin \\>8 gm\u002Fdl (transfusions allowed)\n   3. Platelets \\>50,000\u002FuL (transfusions allowed)\n   4. Absolute Neutrophil Count (ANC) \\> 500\u002FuL\n   5. alanine aminotransferase (ALT)\u002Faspartate aminotransferase (AST) \\\u003C 3 x institutional upper limit of normal (ULN) and Total bilirubin \\\u003C 1.5 mg\u002Fdl x institutional ULN, except with Gilbert's syndrome\n   6. Serum Creatinine \\\u003C 2 x the institutional ULN\n   7. Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) \\> 40% as assessed by echocardiogram or multiple uptake gated acquisition (MUGA) within 3 months of screening. Repeat testing may occur at Investigator's discretion.\n6. Adequate vascular access for leukapheresis procedure (either peripheral line or surgically placed line).\n7. Women of childbearing potential (defined as all women physiologically capable of becoming pregnant) must have a negative serum or urine pregnancy test AND agree to use highly effective methods of contraception for 1 year after the last dose of anti-CD19 CAR-T cells.\n8. Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method.\n9. Ability to understand a written informed consent document, and the willingness to sign it.\n\nExclusion Criteria:\n\n1. Autologous transplant within 6 weeks of planned CAR-T cell infusion.\n2. Recipient of prior CAR-T cell therapy targeting CD19 outside of this protocol.\n3. Active other malignancy, other than non-melanoma skin cancer, carcinoma in situ (e.g., cervix, bladder, or breast).\n4. Human immunodeficiency virus (HIV) seropositivity.\n5. Serologic status reflecting active hepatitis B or C infection. Participants that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive participants will be excluded.)\n6. Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements.\n7. Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study. NOTE: Women of childbearing potential must have a negative serum or urine pregnancy test.\n8. Participants with history of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease.\n9. History of autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months.\n10. Body weight \\\u003C40 kilograms(kg).\n\nEligibility for Infusion of Investigational Product:\n\nParticipants will undergo an evaluation of eligibility on day 1 prior to infusion of anti-CD19 CAR-T cell product. This eligibility criterion will include the inclusion and exclusion criteria required for enrollment with the following exceptions and additions:\n\n1. No significant laboratory abnormalities. Laboratory result abnormalities that are considered not clinically significant by the principal investigator AND are not the result of a demonstrated active infection or an active central nervous system condition.\n2. ECOG performance status \\\u003C 2\n3. No evidence of uncontrolled intercurrent illness including, but not limited to ongoing or active infection, inflammatory response, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness\u002Fsocial situations.\n4. No new neurologic symptoms suggestive of an active central nervous system condition, or uncontrolled CNS involvement by lymphoma.\n5. No corticosteroid use within 7 days prior to infusion (with exception of agents used for prevention of emesis during lymphodepletive chemotherapy).",{"count":328,"type":21},36,[180],"This study will assess safety and feasibility of infusing genetically modified autologous T cells transduced to express a chimeric antigen receptor targeting the B cell surface antigen Cluster of Differentiation 19 (CD19).",[332,249,311,79,81,333,312,28,334,309],"Refractory Non-Hodgkin Lymphoma","Primary Mediastinal Large B Cell Lymphoma","Transformed Lymphoma",[336],"CAR-T Therapy",{"date":338,"type":33},"2026-06-22",{"date":340,"type":33},"2020-09-11",{"date":342,"type":21},"2026-10-31",{"name":344,"class":63},"C. Babis Andreadis",{"id":346,"slug":347,"hasResults":12,"nctId":348,"briefTitle":349,"officialTitle":350,"acronym":351,"eligibilityCriteria":352,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":353,"targetDuration":4,"studyType":22,"phases":355,"briefSummary":356,"conditions":357,"keywords":360,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":365,"lastUpdatePostDateStruct":366,"startDateStruct":367,"completionDateStruct":369,"leadSponsor":371,"locationsCount":373},"100458832","phase-3-a-study-of-pirtobrutinib-loxo-305-versus-ibrutinib-in-participants-with-chronic-lymphocytic-leukemia-cllsmall-lymphocytic-lymphoma-sll-100458832","NCT05254743","A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)\u002FSmall Lymphocytic Lymphoma (SLL)","A Phase 3 Open-Label, Randomized Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Patients With Chronic Lymphocytic Leukemia\u002FSmall Lymphocytic Lymphoma (BRUIN-CLL-314)","BRUIN-CLL-314","Inclusion Criteria:\n\n* Confirmed diagnosis of CLL\u002FSLL requiring therapy per iwCLL 2018 criteria\n* Part 1 - Known 17p deletion status (wildtype or deleted). Part 2 - Must have deletion of 17p as determined by FISH testing\n* Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2\n* Adequate organ function\n\n  * Platelets greater than or equal to ≥ 50 x 10⁹\u002Fliter (L) or ≥30 x 10⁹\u002FL in participants with documented bone marrow involvement considered to impair hematopoiesis,\n  * Hemoglobin ≥8 grams\u002Fdeciliter (g\u002FdL) or ≥6 g\u002FdL in participants with documented bone marrow involvement considered to impair hematopoiesis\n  * Absolute neutrophil count ≥0.75 x 10⁹\u002FL or ≥0.50 × 10⁹\u002FL in participants with documented bone marrow involvement considered to impair hematopoiesis\n  * Kidney function: Estimated creatinine clearance ≥30 milliliters per minute (mL\u002Fmin)\n\nExclusion Criteria:\n\n* Known or suspected Richter's transformation to diffuse large B-cell lymphoma (DLBCL), prolymphocytic leukemia, or Hodgkin's lymphoma at any time preceding enrollment\n* Known or suspected central nervous system (CNS) involvement\n* A significant history of renal, neurologic, psychiatric, endocrine, metabolic or immunologic disease\n* Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia \\[AIHA\\], idiopathic thrombocytopenic purpura \\[ITP\\])\n* Significant cardiovascular disease including ejection fraction \\\u003C 40% and any grade ongoing atrial fibrillation or atrial flutter\n* Hepatitis B or hepatitis C testing indicating active\u002Fongoing infection, based on Screening laboratory tests\n* Active cytomegalovirus (CMV) infection\n* Active uncontrolled systemic bacterial, viral, or fungal infection\n* Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count\n* Clinically significant active malabsorption syndrome or other condition likely to affect GI absorption of the oral-administered study treatments\n* Ongoing inflammatory bowel disease\n* Previous treatment for CLL\u002FSLL - Part 1: Treatment-naïve and previously treated, except prior exposure to BTK inhibitor (covalent or noncovalent).\n\nPart 2: participants must be treatment naïve\n\n* Concurrent use of investigational agent or anticancer therapy except hormonal therapy\n* Participants requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist\n* Use of \\> 20 mg prednisone daily or equivalent dose of steroid at the time of first dose of study drug\n* Vaccination with a live vaccine within 28 days prior to randomization\n* Participants receiving chronic therapy with a strong cytochrome P450 (CYP)3A inhibitor (except posaconazole and voriconazole) which cannot be stopped within 3-5 half lives of the CYP3A inhibitor therapy prior to start of study drug treatment\n* Participants with known hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib or ibrutinib",{"count":354,"type":21},737,[24],"The purpose of Part 1 of this study is to compare the efficacy and safety of pirtobruitinib (LOXO-305) to ibrutinib in participants with CLL\u002FSLL; participants may or may not have already had treatment for their cancer. The purpose of Part 2 of this study evaluates pirtobrutinib monotherapy in treatment-naïve participants with CLL\u002FSLL with 17p deletions. Participation could last up to six years for Part 1. Participation could last up to 2 years for Part 2.",[27,358,359,28],"Leukemia, Lymphocytic","Leukemia, B-cell",[361,362,363,364],"BTKi","Hematologic Disease","Lymphoma, non-Hodgkin's","Lymphoma, B-cell","2026-06-16",{"date":285,"type":33},{"date":368,"type":33},"2022-07-22",{"date":370,"type":21},"2028-01",{"name":372,"class":142},"Loxo Oncology, Inc.",143,{"id":375,"slug":376,"hasResults":12,"nctId":377,"briefTitle":378,"officialTitle":379,"acronym":4,"eligibilityCriteria":380,"healthyVolunteers":381,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":382,"targetDuration":4,"studyType":22,"phases":384,"briefSummary":386,"conditions":387,"keywords":389,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":392,"lastUpdatePostDateStruct":393,"startDateStruct":394,"completionDateStruct":396,"leadSponsor":398,"locationsCount":64},"100564976","early-phase-1-64cu-llp2a-for-imaging-hematologic-malignancies-100564976","NCT06636175","64Cu-LLP2A for Imaging Hematologic Malignancies","Early Phase I Evaluation of 64Cu-LLP2A for Imaging Hematologic Malignancies Part B","Inclusion Criteria Healthy Volunteer:\n\n* Adult 18 years of age or older\n* Able to give informed consent.\n* Able to comprehend and willing to follow instructions for study procedures as called for by the protocol\n* Capable of lying still and supine within the PET\u002FCT scanner for up to 75 minutes.\n* No illicit drug use or other inhaled drug use (including pharmacologic agents and illicit drugs) within the past year per self-reporting mechanisms.\n* No history of claustrophobia or other condition that has previously or would interfere with completion of protocol specified imaging sessions.\n* Not currently pregnant or nursing: Subject must be surgically sterile (has had a documented bilateral oophorectomy and\u002For documented hysterectomy), post-menopausal (cessation of menses for more than 1 year), non-lactating, or of childbearing potential for whom a urine pregnancy test (with the test performed within the 24 hour period immediately prior to administration of 64Cu-LLP2A) is negative.\n\nInclusion Criteria Hematological Malignancy:\n\n* Clinical or pathologically defined MM or lymphoma including both newly diagnosed, relapsed or refractory disease:\n\n  * Multiple Myeloma defined in accordance with the International Myeloma Working Group criteria\n  * Low-grade lymphoma, including the following subtypes: follicular lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma, small lymphocytic lymphoma\u002Fchronic lymphocytic leukemia\n* Adult 18 years of age or older and able to provide informed consent\n* Capable of lying still and supine within the PET\u002FCT scanner for up to 75 minutes.\n* No history of claustrophobia or other condition that has previously or would interfere with completion of protocol specified imaging sessions\n* Not currently pregnant or nursing: Subject must be surgically sterile (has had a documented bilateral oophorectomy and\u002For documented hysterectomy), post-menopausal (cessation of menses for more than 1 year), non-lactating, or of childbearing potential for whom a urine pregnancy test (with the test performed within the 24 hour period immediately prior to administration of 64Cu-LLP2A) is negative\n* Patients participating in imaging or therapeutic trials with investigational agents are eligible to participate",true,{"count":383,"type":21},42,[385],"EARLY_PHASE1","This phase of the protocol (protocol part B), seeks to evaluate the new formulation in healthy normal volunteers to confirm the new formulation provides comparable human dosimetry to which was seen and published in protocol part A. Additionally, the new formulation will be studied utilizing an expanded patient population to include patients with confirmed diagnosis of multiple myeloma (MM), low-grade lymphoma, or MM and lymphoma patients who are status post bone marrow transplant (BMT) with negative imaging and suspected recurrence.",[251,388,79,80,81,28,27],"Low-Grade Lymphoma",[390,391],"PET","Imaging","2026-06-15",{"date":285,"type":33},{"date":395,"type":33},"2025-03-20",{"date":397,"type":21},"2027-03-31",{"name":399,"class":63},"Washington University School of Medicine",{"id":401,"slug":402,"hasResults":12,"nctId":403,"briefTitle":404,"officialTitle":405,"acronym":406,"eligibilityCriteria":407,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":408,"targetDuration":4,"studyType":22,"phases":410,"briefSummary":411,"conditions":412,"keywords":417,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":428,"lastUpdatePostDateStruct":429,"startDateStruct":431,"completionDateStruct":433,"leadSponsor":435,"locationsCount":437},"100559431","phase-1-a-study-of-azd0486-monotherapy-or-in-combination-with-other-anti-cancer-agents-for-mature-b-cell-malignancies-100559431","NCT06564038","A Study of AZD0486 Monotherapy or in Combination With Other Anti-Cancer Agents for Mature B-Cell Malignancies","A Phase I\u002FII Open-Label Multi-Centre Master Protocol to Evaluate the Safety and Efficacy of AZD0486 Monotherapy or in Combination With Other Anticancer Agents in Participants With Mature B-Cell Malignancies","Soundtrack-E","Inclusion Criteria:\n\nMaster Inclusion Criteria applicable to all substudies:\n\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.\n* Contraception use during treatment and at least 90 days after final dose.\n* Confirmed CD19 expression if prior anti-CD19 therapy.\n\nSubstudy 1 Specific Inclusion Criteria:\n\n* Participants with CLL must require treatment according to the international workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria.\n* SLL: at least 1 measurable site per Lugano.\n* Absolute lymphocyte count (ALC) \\\u003C25000 cells\u002FmcL.\n* Cohort 1A and 1C: at least 2 prior lines of systemic therapy for CLL\u002FSLL.\n* Cohort 1B: at least 1 prior line of therapy and is bruton tyrosine kinase inhibitor (BTKi)-sensitive.\n\nSubstudy 2 Specific Inclusion Criteria:\n\n* MCL diagnosis per WHO.\n* Clinical Stage II, III, or IV by Ann Arbor Classification.\n* At least 1 measurable site per Lugano.\n* ALC \\\u003C 25000 cells\u002FmcL.\n* Cohort 2A and 2C: Relapse or progressed after 2 or more lines of therapy including BTKi.\n\nSubstudy 3 Specific Inclusion Criteria:\n\n* At least 1 measurable site as per Lugano.\n* Left ventricular ejection fraction (LVEF) ≥50%.\n* Participant must be no older than 79 years of age at the time of signing ICF.\n* Contraception at least 90 days after last dose of surovatamig or 4 months after last dose of vincristine, and 6 months after the last dose of cyclophosphamide, or doxorubicin.\n* Cohort 3A:\n\n  1. Histologically confirmed diagnosis of previously untreated large B-cell Lymphoma (LBCL) per WHO 2022.\n  2. R\u002FR B-NHL after at least 1 prior lines of systemic therapy.\n  3. International Prognostic Index (IPI) 2-5.\n* Cohort 3B:\n\n  1. Histologically confirmed diagnosis of previously untreated large B-cell Lymphoma (LBCL) per WHO 2022.\n  2. IPI score of 2 to 5.\n\nExclusion Criteria:\n\nMaster Exclusion Criteria applicable to all substudies:\n\n* Central nervous system (CNS) lymphoma.\n* Surgery within 14 days of study drug.\n* Clinically significant cardiovascular (CV) disease.\n* Unresolved Grade \\>2 AEs from prior anticancer therapy (except alopecia or fatigue).\n* Any systemic therapy within 5 half-lives or 21 days (whichever is shorter) prior to treatment.\n* Radiation therapy within 28 days.\n* Prior CAR T-cell therapy or autologous-haematopoietic stem cell transplant (HSCT) within 12 weeks or prior T-cell engager (TCE) within 8 weeks.\n* Prior Grade \\> 3 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) event.\n* Prior allogeneic HSCT or solid organ transplantation within 24 weeks of starting Cycle 1 Day 1.\n* Active, significant, uncontrolled infection or autoimmune disease requiring systemic therapy including participants with known history of haemophagocytic lymphohistiocytosis (HLH).\n\nSubstudy 1 Specific Exclusion Criteria:\n\n* CLL\u002FSLL transformation to more aggressive form of lymphoma.\n* Cohort 1B: bleeding diathesis, CYP3A inhibitor or inducer, history of ICH or stroke within 24 weeks, GI malabsorption, receiving vitamin K antagonist.\n\nSubstudy 3 Specific Exclusion Criteria:\n\n* Mediastinal grey-zone lymphoma, Burkitt, Richter's transformation, primary effusion large B-cell lymphoma (LBCL).\n* Cumulative dose of anthracycline \\>150 mg\u002Fm2.",{"count":409,"type":21},408,[180,51],"The purpose of this study is to assess the safety and efficacy of surovatamig (formerly AZD0486) administered as monotherapy or in combination with other anticancer agents in participants with hematological malignancies",[413,28,414,415,416],"Chronic Lymphocytic Leukaemia","Mantle-cell Lymphoma","Large B-cell Lymphoma","B-cell Non-Hodgkin Lymphoma",[418,419,420,421,422,423,424,425,426,427],"IgG4 fully human CD19xCD3 bispecific T-cell engager","B cell lymphoma","Subcutaneous","Acalabrutinib","Prednisone","Rituximab","Cyclophosphamide","Vincristine","Doxorubicin","Surovatamig","2026-06-09",{"date":430,"type":33},"2026-06-10",{"date":432,"type":33},"2025-01-30",{"date":434,"type":21},"2029-06-11",{"name":436,"class":142},"AstraZeneca",64,{"id":439,"slug":440,"hasResults":12,"nctId":441,"briefTitle":442,"officialTitle":442,"acronym":443,"eligibilityCriteria":444,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":445,"targetDuration":4,"studyType":22,"phases":447,"briefSummary":448,"conditions":449,"keywords":450,"overallStatus":54,"whyStopped":4,"lastUpdateSubmitDate":452,"lastUpdatePostDateStruct":453,"startDateStruct":455,"completionDateStruct":457,"leadSponsor":459,"locationsCount":64},"100633431","phase-2-study-on-treatment-outcome-patterns-for-patients-with-cll-after-discontinuation-of-btk-inhibitors-100633431","NCT07526597","Study on Treatment Outcome Patterns for Patients With CLL After Discontinuation of BTK Inhibitors","STOP-CLL-DCT","Inclusion Criteria:\n\nIn order to participate in this study a subject must meet all of the eligibility criteria outlined below.\n\n* Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.\n* Subjects is willing and able to comply with study procedures based on the judgement of the investigator.\n* Age ≥ 18 years at the time of consent.\n* Eastern Cooperative Oncology Group Performance Status of 0-3 or Karnofsky Performance Status of ≥40\n* Confirmed of a diagnosis of CLL (Chronic Lymphocytic Leukemia) or SLL (Small Lymphocytic Lymphoma) according to International Workshop on Chronic Lymphocytic Leukemia 2018 Guidelines at any point prior to study enrollment.\n* At the time of enrollment, patients must be receiving treatment with a covalent Bruton tyrosine kinase inhibitor in the first or second line setting and have been receiving this treatment for at a minimum 2 years. Patients may have previously received anti-CD20 monoclonal antibodies (such as rituximab or obinutuzumab) in combination with the cBTKi.\n\nExclusion Criteria:\n\n* Patients must not have evidence of progressive CLL as defined by IWCLL 2018 criteria.\n* Participants with history of malignancy other than CLL\u002FSLL are allowed",{"count":446,"type":21},45,[51],"This Phase II hybrid decentralized multicenter study examines the outcomes of stopping Bruton tyrosine kinase inhibitor (BTKi) therapy in patients with chronic lymphocytic leukemia (CLL) who have remained in remission for at least two years. The primary objective is to determine how long patients remain free from disease progression or death after discontinuing treatment, measured as event free survival.\n\nThe study also evaluates whether stopping BTKi therapy leads to improvements in quality of life and reductions in treatment related side effects. Researchers will follow patients over time to assess if the cancer returns, whether resistance to therapy develops, and how patients feel during the treatment free period.\n\nIn addition, the trial will investigate how discontinuing BTKi therapy affects immune function, including whether immune recovery occurs and infection risk decreases.\n\nPreliminary data indicate that patients may experience a treatment free interval exceeding two years after stopping therapy, with associated improvements in quality of life. By prospectively evaluating a time limited treatment strategy, this trial aims to determine whether durable disease control can be maintained off therapy while also assessing the resolution of BTKi related adverse events and changes in patient reported outcomes.\n\nOverall, the study seeks to determine whether patients can safely discontinue BTKi therapy and potentially restart treatment later if needed, thereby maintaining disease control while reducing the burden of continuous therapy.",[27,28],[451],"Bruton's tyrosine kinase inhibitors (BTKi)","2026-06-04",{"date":454,"type":33},"2026-06-08",{"date":456,"type":21},"2026-07",{"date":458,"type":21},"2032-06",{"name":93,"class":63},{"id":461,"slug":462,"hasResults":12,"nctId":463,"briefTitle":464,"officialTitle":465,"acronym":466,"eligibilityCriteria":467,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":468,"targetDuration":4,"studyType":22,"phases":470,"briefSummary":471,"conditions":472,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":452,"lastUpdatePostDateStruct":473,"startDateStruct":475,"completionDateStruct":477,"leadSponsor":479,"locationsCount":481},"100513254","phase-2-a-study-to-customize-ibrutinib-treatment-regimens-for-participants-with-previously-untreated-chronic-lymphocytic-leukemia-100513254","NCT05963074","A Study to Customize Ibrutinib Treatment Regimens for Participants With Previously Untreated Chronic Lymphocytic Leukemia","Multicohort Study to Customize Ibrutinib Treatment Regimens for Patients With Previously Untreated Chronic Lymphocytic Leukemia","TAILOR","Inclusion Criteria:\n\n* Diagnosis of chronic lymphocytic leukemia\u002F small lymphocytic lymphoma (CLL\u002FSLL) as per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 diagnostic criteria\n* For ibruinib + venetocIax (I+V) cohorts: eastern cooperative oncology group (ECOG) performance status of 0-1. For ibrutinib monotherapy cohorts: ECOG performance status of 0-2\n* Measurable nodal disease by computed tomography (CT), defined as at least 1 lymph node greater than and equal to (\\>=) 1.5 centimeters (cm) in longest diameter\n* A participant using oral contraceptives must use an additional contraceptive method\n* A participant must agree not to be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or until 1 month after last dose or per local label if more conservative (for example, 3 months in European Union or Canada and 1 month in United States)\n\nExclusion Criteria:\n\n* Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura, such as those participants with a declining hemoglobin level or platelet count secondary to autoimmune destruction within the 4 weeks prior to first dose of study treatment, or the need for prednisone greater than (\\>) 20 milligrams (mg) daily (or corticosteroid equivalent) to treat or control the autoimmune disease\n* Known bleeding disorders (example, von Willebrand's disease or hemophilia)\n* Stroke or intracranial hemorrhage within 6 months prior to enrollment\n* Known or suspected Richter's transformation or central nervous system (CNS) involvement\n* Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class II, III, or IV congestive heart failure as defined by the New York Heart Association Functional Classification",{"count":469,"type":21},320,[51],"The purpose of this study is to evaluate the efficacy and safety of ibrutinib + venetoclax (I+V) and ibrutinib monotherapy regimens in which dosing of ibrutinib is either proactively reduced or reactively modified in response to adverse events (AEs).",[183,28],{"date":474,"type":33},"2026-06-05",{"date":476,"type":33},"2024-05-30",{"date":478,"type":21},"2029-03-19",{"name":480,"class":142},"Janssen Research & Development, LLC",74,{"id":483,"slug":484,"hasResults":12,"nctId":485,"briefTitle":486,"officialTitle":487,"acronym":488,"eligibilityCriteria":489,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":490,"targetDuration":4,"studyType":22,"phases":492,"briefSummary":493,"conditions":494,"keywords":497,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":452,"lastUpdatePostDateStruct":508,"startDateStruct":509,"completionDateStruct":511,"leadSponsor":513,"locationsCount":514},"100194258","phase-3-a-long-term-extension-study-of-pci-32765-ibrutinib-100194258","NCT01804686","A Long-term Extension Study of PCI-32765 (Ibrutinib)","A Phase 3b, Multicenter, Open-label, PCI-32765 (Ibrutinib) Long-term Extension Study","CAN3001","Inclusion Criteria:\n\n* Participants must be currently participating in an ibrutinib clinical study considered complete and have received at least 6 months of treatment with ibrutinib. At study entry, participants must be actively receiving treatment with single-agent ibrutinib; or participants must have participated in an ibrutinib randomized clinical study in which they initially received comparator treatment and now cross-over to ibrutinib. Note: A minimum of 6 months requirement for prior ibrutinib treatment will not be mandatory in this case and participants with less than 6 months will be required to have more frequent initial safety assessments; or participants must be currently participating in study PCI-32765LYM1002. At study entry, participants must be actively receiving combination treatment with ibrutinib and nivolumab or single-agent ibrutinib\n* Investigator's assessment that the benefit of continued ibrutinib therapy as a single agent or in combination with nivolumab will outweigh the risks\n* Agrees to protocol-defined use of effective contraception\n* Negative blood or urine pregnancy test at screening\n\nExclusion Criteria:\n\n* Requires anticoagulation with warfarin or equivalent vitamin K antagonists\n* Requires treatment with strong cytochrome P450 (CYP)3A4\u002F5 inhibitors, unless previously approved by sponsor\n* Any condition or situation which, in the opinion of the investigator, may put the participant at significant risk, may confound the study results, or may interfere significantly with volunteer's participation in the study",{"count":491,"type":21},700,[24],"The purpose of this study is to collect long-term safety and efficacy data for participants treated with ibrutinib and to provide ongoing access to ibrutinib for participants who are currently enrolled in ibrutinib studies that have been completed according to the parent protocol, are actively receiving treatment with ibrutinib, and who continue to benefit from ibrutinib treatment.",[27,28,311,79,495,82,496],"Diffuse Large B-cell Lymphoma","Chronic Graft Versus Host Disease",[498,499,500,501,502,503,504,505,506,507],"Chronic lymphocytic leukemia","Small lymphocytic lymphoma","Mantle cell lymphoma","Follicular lymphoma","Diffuse large B-cell lymphoma","PCI-32765","Ibrutinib","Bruton's tyrosine kinase inhibitor","IMBRUVICA","JNJ-54179060",{"date":474,"type":33},{"date":510,"type":33},"2013-09-09",{"date":512,"type":21},"2029-12-31",{"name":480,"class":142},175,{"id":516,"slug":517,"hasResults":12,"nctId":518,"briefTitle":519,"officialTitle":520,"acronym":4,"eligibilityCriteria":521,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":522,"targetDuration":4,"studyType":22,"phases":524,"briefSummary":525,"conditions":526,"keywords":527,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":531,"lastUpdatePostDateStruct":532,"startDateStruct":533,"completionDateStruct":535,"leadSponsor":537,"locationsCount":538},"100588628","phase-3-a-study-to-investigate-progression-free-survival-with-sonrotoclax-plus-obinutuzumab-or-sonrotoclax-plus-rituximab-compared-with-venetoclax-plus-rituximab-treatment-in-patients-with-relapsed-andor-refractory-chronic-lymphocytic-leukemiasmall-lymphocytic-lymphoma-celestial-rrcll-100588628","NCT06943872","A Study to Investigate Progression-Free Survival With Sonrotoclax Plus Obinutuzumab Or Sonrotoclax Plus Rituximab Compared With Venetoclax Plus Rituximab Treatment In Patients With Relapsed and\u002For Refractory Chronic Lymphocytic Leukemia\u002FSmall Lymphocytic Lymphoma (CELESTIAL-RRCLL)","A Phase 3 Randomized, Open-Label, Multicenter Study of Sonrotoclax Plus Anti-CD20 Antibody Therapies Versus Venetoclax Plus Rituximab in Patients With Relapsed\u002FRefractory Chronic Lymphocytic Leukemia\u002FSmall Lymphocytic Lymphoma","Inclusion Criteria:\n\n* Confirmed diagnosis of CLL\u002FSLL that meets the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria\n* Received one or more prior therapies for CLL\u002FSLL. For each line of therapy, participants must have received at least 2 cycles of the therapy\n* Participants with prior BCL2i exposure are eligible if remission duration was ≥3 years with ≥2 years from last BCL2i intake\n* Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2\n* Adequate organ function\n\nExclusion Criteria:\n\n* Known active prolymphocytic leukemia or currently suspected Richter's transformation\n* Prior autologous stem cell transplantation or chimeric antigen receptor T-cell therapy within 3 months before first dose of study drug\n* Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD), requiring immunosuppressive drugs for treatment of GVHD, or have taken calcineurin inhibitors within 4 weeks prior to consent\n* Known central nervous system involvement by CLL\u002FSLL\n* Severe or debilitating pulmonary disease\n* Clinically significant cardiovascular disease\n\nNOTE: Other protocol defined Inclusion\u002FExclusion criteria may apply.",{"count":523,"type":21},630,[24],"The goal of this study is to compare how well sonrotoclax plus obinutuzumab works versus venetoclax plus rituximab in treating adults with relapsed and\u002For refractory (R\u002FR) chronic lymphocytic leukemia\u002Fsmall lymphocytic lymphoma (CLL\u002FSLL). The study will also compare how well sonrotoclax plus rituximab works versus venetoclax plus rituxumab in treating adults with R\u002FR CLL\u002FSLL. The safety of these treatments will also be assessed.",[27,28],[528,529,530],"B-cell lymphoma 2 inhibitor (BCL-2i)","CLL-RR1","German CLL Study Group","2026-06-03",{"date":452,"type":33},{"date":534,"type":33},"2025-06-11",{"date":536,"type":21},"2031-12",{"name":293,"class":142},173,{"id":540,"slug":541,"hasResults":12,"nctId":542,"briefTitle":543,"officialTitle":544,"acronym":4,"eligibilityCriteria":545,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":546,"targetDuration":4,"studyType":22,"phases":548,"briefSummary":549,"conditions":550,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":551,"lastUpdatePostDateStruct":552,"startDateStruct":554,"completionDateStruct":556,"leadSponsor":558,"locationsCount":559},"100561308","phase-2-a-study-evaluating-the-efficacy-and-safety-of-pirtobrutinib-in-participants-with-relapsed-or-refractory-chronic-lymphocytic-leukemiasmall-lymphocytic-lymphoma-100561308","NCT06588478","A Study Evaluating the Efficacy and Safety of Pirtobrutinib in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia\u002FSmall Lymphocytic Lymphoma","A Phase 2, Open-Label, Randomized Study Evaluating the Efficacy and Safety of 3 Doses of Pirtobrutinib in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia\u002FSmall Lymphocytic Lymphoma Who Previously Received Treatment With a Covalent Bruton Tyrosine Kinase Inhibitor","Inclusion Criteria:\n\n* Have confirmed diagnosis of CLL\u002FSLL as defined by iwCLL 2018 criteria.\n* Part 1: Have received prior CLL\u002FSLL treatment\n* Have received at least 1, but not more than 3 lines of prior treatment for CLL\u002FSLL\n* Have received a covalent BTK inhibitor\n* Part 2: Have received no prior treatment for CLL\u002FSLL\n\n  * Part 1 - Known 17p deletion status (positive or negative)\n  * Part 2 - Must have 17p deletion (positive)\n* Have a requirement for therapy consistent with iwCLL 2018 criteria for initiation of therapy\n* Capable of swallowing oral study medication.\n* Have an Eastern Cooperative Oncology Group Performance Status (ECOG) score of 0 to 2.\n\nExclusion Criteria:\n\n* Have received prior treatment with a BTK degrader or a noncovalent BTK inhibitor\n* Have a history of greater than or equal to (\\>=) Grade 3 bleeding due to treatment with a BTK inhibitor\n* Have known or suspected Richter's transformation\n* Have known or suspected history of central nervous system involvement by CLL\u002FSLL\n* Previous or concurrent cancer distinct from CLL\u002FSLL within 3 years before randomization. Exceptions may occur with documented sponsor approval. Examples include:\n\n  * nonmelanoma skin cancer or lentigo malignant melanoma\n  * cervical carcinoma in situ\n  * localized prostate cancer undergoing active surveillance, and\n  * localized (for example, lymph node negative) breast cancer with no evidence of active disease present for more than 3 years. Individual may be receiving adjuvant hormonal therapy",{"count":547,"type":21},249,[51],"The main purpose of Part 1 of this study is to assess the efficacy and safety of 3 dose levels of Pirtobrutinib in participants with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), who have received 1-3 lines of treatment including a covalent Bruton tyrosine kinase (BTK) inhibitor. The purpose of Part 2 of this study is to evaluate pirtobrutinib monotherapy in participants with treatment-naïve CLL\u002FSLL with 17p deletions. Participation in Part 1 is expected to last approximately 3 years. Participation in Part 2 is expected to last up to 2 years.",[27,28],"2026-05-18",{"date":553,"type":33},"2026-05-19",{"date":555,"type":33},"2025-01-03",{"date":557,"type":21},"2028-12",{"name":372,"class":142},131,{"id":561,"slug":562,"hasResults":12,"nctId":563,"briefTitle":564,"officialTitle":565,"acronym":4,"eligibilityCriteria":566,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":567,"targetDuration":4,"studyType":22,"phases":569,"briefSummary":570,"conditions":571,"keywords":4,"overallStatus":54,"whyStopped":4,"lastUpdateSubmitDate":573,"lastUpdatePostDateStruct":574,"startDateStruct":576,"completionDateStruct":578,"leadSponsor":580,"locationsCount":582},"100639384","phase-2-tafasitamab-with-acalabrutinib-and-venetoclax-for-the-treatment-of-chronic-lymphocytic-leukemiasmall-lymphocytic-lymphoma-100639384","NCT07582159","Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia\u002FSmall Lymphocytic Lymphoma","A Phase 2 Study of Acalabrutinib, Venetoclax and Tafasitamab (AVT) in Patients With Previously Untreated Chronic Lymphocytic Leukemia\u002FSmall Lymphocytic Lymphoma (CLL\u002FSLL)","Inclusion Criteria:\n\n* Documented informed consent of the participant and\u002For legally authorized representative.\n\n  * Assent, when appropriate, will be obtained per institutional guidelines\n* Agreement to allow the use of archival tissue from diagnostic tumor biopsies\n\n  * If unavailable, exceptions may be granted with study principal investigator (PI) approval\n* Age: ≥ 18 years\n* Eastern Cooperative Oncology Group (ECOG) ≤ 2\n* Histologically or flow cytometry confirmed diagnosis of B-CLL\u002FSLL as documented by medical records and with histology based on criteria established by the World Health Organization (WHO)\n* No prior treatment for CLL\u002FSLL, except steroids and\u002For rituximab to treat autoimmune complications\n* Active disease meeting criteria for requiring treatment per the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines\n\n  * A minimum of any one of the following constitutional symptoms:\n\n    * Unintentional weight loss \\> 10% within the previous 6 months prior to screening.\n    * Extreme fatigue (unable to work or perform usual activities).\n    * Fevers of greater than 100.5°F for ≥ 2 weeks without evidence of infection.\n    * Night sweats without evidence of infection.\n  * Evidence of progressive marrow failure as manifested by the development of, or worsening of anemia or thrombocytopenia.\n  * Massive (i.e., \\> 6 cm below the left costal margin), progressive or symptomatic splenomegaly.\n  * Massive nodes or clusters (i.e., \\> 10 cm in longest diameter) or progressive lymphadenopathy.\n  * Progressive lymphocytosis with an increase of \\> 50% over a 2-month period, or an anticipated doubling time of less than 6 months.\n  * Autoimmune anemia or thrombocytopenia that is poorly responsive to corticosteroids.\n  * Symptomatic or functional extranodal involvement (eg, skin, kidney, lung, spine)\n* Participant must be able to swallow tablets or capsules. A participant with any gastrointestinal disease that would impair ability to swallow, retain, or absorb drug is not eligible\n* Absolute neutrophil count (ANC) ≥ 500\u002Fmm\\^3\n* Platelets ≥ 30,000\u002Fmm\\^3\n* Total bilirubin ≤ 2 X upper limit of normal (ULN) (unless has Gilbert's disease or compensated hemolysis directly attributable to CLL)\n* Aspartate aminotransferase (AST) ≤ 2.5 x ULN\n* Alanine aminotransferase ≤ 2.5 x ULN\n* Creatinine clearance of ≥ 30 mL\u002Fmin per 24 hour urine test or the Cockcroft-Gault formula\n* If not receiving anticoagulants: International Normalized Ratio (INR) OR Prothrombin (PT) ≤ 1.5 x ULN. If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants\n* If not receiving anticoagulants: Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN. If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants\n* If seropositive for HIV, hepatitis C virus (HCV) or hepatitis B virus (HBV), nucleic acid quantitation must be performed. Viral load must be undetectable. HIV-infected patients on active anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required\n* Agreement by females and males of childbearing potential\\* to use an effective method of birth control or abstain from heterosexual activity for the course of the study and after completion of study treatment as described below separately for males and females.\n\n  * Female participants must remain abstinent or use contraceptive methods with a failure rate of \\\u003C 1% per year during the treatment period and for at least 2 days after the final dose of acalabrutinib, 30 days after the last dose of venetoclax, and 3 months after the final dose of tafasitamab, whichever is longer. Women must refrain from donating eggs during this same period.\n\n    * Examples of contraceptive methods with a failure rate of \\\u003C 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.\n    * Hormonal contraceptive methods must be supplemented by a barrier method.\n  * For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agree to refrain from donating sperm, as defined below:\n\n    * With a female partner of childbearing potential or pregnant female partners, male participants must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \\\u003C 1% per year during the treatment period and for at least 2 days after the final dose of acalabrutinib, 90 days after the last dose of venetoclax, and 3 months after the final dose of tafasitamab, whichever is longer. Male participants must refrain from donating sperm during this same period.\n  * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception.\n  * A woman is considered of childbearing potential, ie, fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. Contraception methods include the following:\n\n    * Combined (estrogen- and progestogen- containing) hormonal contraception associated with the inhibition of ovulation\n\n      * Oral, intravaginal, or transdermal\n    * Progestogen-only hormonal contraception associated with the inhibition of ovulation\n\n      * Oral, injectable, implantable\n    * An intrauterine device\n    * Intrauterine hormone-releasing system\n    * Bilateral tubal occlusion Vasectomized partner (provided that the vasectomized partner is the sole sexual partner of the woman of childbearing potential study participant and that the vasectomized partner has received medical assessment of surgical success)\n    * Sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment, starting the day prior to first dose of study drug, for the duration of the study, and for ≥ 90 days after the last dose of zanubrutinib or ibrutinib. Total sexual abstinence should only be used as a contraceptive method if it is in line with the patients' usual and preferred lifestyle. Of note, barrier contraception (including male and female condoms with or without spermicide) is not considered a highly effective method of contraception, and, if used, this method must be used in combination with another acceptable method listed above. If patient is using hormonal contraceptives such as birth control pills or devices, a barrier method of contraception (eg, condoms) must also be used. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single follicle-stimulating hormone measurement is insufficient\n\nExclusion Criteria:\n\n* Chronic use of corticosteroids in excess of 20 mg\u002Fday prednisone or its equivalent\n* Major surgery (under general anesthesia) within 30 days prior to therapy\n* Uncontrolled coagulopathy or bleeding disorder. Direct oral anticoagulants are allowed\n* Use of moderate or strong cytochrome P450 3A4 (CYP3A4) inducer within 2 weeks of the first day of study therapy. CYP3A inhibitors are allowed\n* Exposure to vaccination with live vaccine within 30 days prior to cycle (C) 1 day (D) 1, or anticipated need for such vaccination during treatment\n* History of prior malignancy except:\n\n  * Malignancy treated with curative intent and no known active disease present for ≥ 2 years prior to initiation of therapy on current study;\n  * Adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease\n  * Adequately treated in situ carcinomas (e.g., cervical, esophageal, etc.) without evidence of disease;\n  * Asymptomatic prostate cancer managed with \"watch and wait\" strategy;\n* Uncontrolled immune hemolysis or thrombocytopenia (positive direct antiglobulin test in absence of hemolysis or history of immune-mediated cytopenias are not exclusions)\n* Active infection\n* Known positive test result for hepatitis C (HCV antibody serology testing) and a positive test result for HCV ribonucleic acid (RNA). Participants with positive serology are eligible in case of negative HCV RNA test results\n* Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Patients with past HBV infection (defined as negative hepatitis B surface antigen (HBsAg) and positive hepatitis B core antibody \\[HBcAb\\]) are eligible if HBV deoxyribonucleic acid (DNA) is undetectable. Patients who are positive for HCV antibody are eligible if polymerase chain reaction (PCR) is negative for HCV RNA\n* Known active human immunodeficiency virus (HIV) infection. Subjects who have an undetectable or unquantifiable HIV viral load with CD4 \\> 200 and are on highly active antiretroviral therapy (HAART) medication are allowed. Testing to be done only in patients suspected of having infections or exposures\n* Females only: Pregnant or breastfeeding\n* Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures\n* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility\u002Flogistics)",{"count":568,"type":21},35,[51],"This phase II trial tests the safety, side effects and how well giving tafasitamab with acalabrutinib and venetoclax works for the treatment of chronic lymphocytic leukemia (CLL)\u002Fsmall cell lymphoma (SLL). A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Tafasitamab is a monoclonal antibody that binds to CD19 antigen which is found on the surface of most B cells (a type of white blood cell) and some lymphoma cells. This may help the immune system kill cancer cells. Acalabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers such as mantle cell lymphoma at abnormal levels. This may help keep cancer cells from growing and spreading. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving tafasitamab with acalabrutinib and venetoclax may be safe and effective for treating patients with CLL\u002FSLL.",[27,572,28],"Chronic Lymphocytic Leukemia\u002FSmall Lymphocytic Lymphoma","2026-05-06",{"date":575,"type":33},"2026-05-12",{"date":577,"type":21},"2026-12-19",{"date":579,"type":21},"2029-04-14",{"name":581,"class":63},"City of Hope Medical Center",2,{"id":584,"slug":585,"hasResults":12,"nctId":586,"briefTitle":587,"officialTitle":588,"acronym":4,"eligibilityCriteria":589,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":590,"targetDuration":4,"studyType":103,"phases":4,"briefSummary":591,"conditions":592,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":593,"lastUpdatePostDateStruct":594,"startDateStruct":595,"completionDateStruct":597,"leadSponsor":598,"locationsCount":601},"100467825","economic-analysis-of-early-vs-delayed-therapy-in-newly-diagnosed-asymptomatic-high-risk-patients-with-chronic-lymphocytic-leukemiasmall-lymphocytic-lymphoma-100467825","NCT05371808","Economic Analysis of Early vs Delayed Therapy in Newly Diagnosed Asymptomatic High-Risk Patients With Chronic Lymphocytic Leukemia\u002FSmall Lymphocytic Lymphoma:","An Economic Analysis of Early vs Delayed Therapy in Newly Diagnosed Asymptomatic High-Risk Patients With Chronic Lymphocytic Leukemia\u002FSmall Lymphocytic Lymphoma: A Companion Analysis to CCTG CLC.3\u002FSWOG 1925 Randomized Phase III Clinical Trial","Inclusion Criteria:\n\n* Patient must be eligible for the core CLC3\u002FS1925 protocol.\n* Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.\n* Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life and\u002For health utility questionnaires in either English or French. The baseline assessment must be completed within required timelines, prior to enrollment. Inability (lack of comprehension in English or French, or other equivalent reason such as cognitive issues or lack of competency) to complete the questionnaires will not make the patient ineligible for the study. However, ability but unwillingness to complete the questionnaires will make the patient ineligible.\n* Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.",{"count":20,"type":21},"Utilization data will be collected from all patients entered on the trial at Canadian centres from the time of registration until death, removal from study, or completion of 10 years of follow-up.\n\nProtocol-specified health care utilization will be collected within trial case report forms, and will include study visits, radiographic assessments, laboratory investigations, and treatment administration.\n\nResource utilization data collection will be supplemented by a self-administered resource utilization form (Stanford SMRC) to document non-protocol specified utilization. This will include hospitalizations (including days in hospital), emergency room visits, and non-protocol specified ambulatory visits.",[27,28],"2026-05-05",{"date":573,"type":33},{"date":596,"type":33},"2023-01-27",{"date":37,"type":21},{"name":599,"class":600},"Canadian Cancer Trials Group","NETWORK",8,{"id":603,"slug":604,"hasResults":12,"nctId":605,"briefTitle":606,"officialTitle":607,"acronym":4,"eligibilityCriteria":608,"healthyVolunteers":12,"sex":17,"minAge":609,"maxAge":4,"enrollmentInfo":610,"targetDuration":4,"studyType":22,"phases":612,"briefSummary":613,"conditions":614,"keywords":623,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":627,"lastUpdatePostDateStruct":628,"startDateStruct":629,"completionDateStruct":631,"leadSponsor":632,"locationsCount":601},"100421728","phase-1-study-of-oral-administration-of-lp-118-in-patients-with-relapsed-or-refractory-cll-sll-mds-mdsmpn-aml-cmml-2-mpn-bp-all-mf-nhl-rt-mm-or-t-pll-100421728","NCT04771572","Study of Oral Administration of LP-118 in Patients With Relapsed or Refractory CLL, SLL, MDS, MDS\u002FMPN, AML, CMML-2, MPN-BP, ALL, MF, NHL, RT, MM or T-PLL.","A Phase 1\u002F1b Study Evaluating the Safety, Pharmacokinetics, and Preliminary Efficacy of LP-118 in Subjects With Relapsed or Refractory Hematological Malignancies","Inclusion Criteria:\n\n1. Male or female subjects, ≥ 18 years of age at the time of Screening with the following exception as outlined below:\n\n   -For T cell and B cell ALL subjects with age between 13 - 18 years, their body weight shall be ≥ 40 kg.\n2. Eligible subject must have an advanced hematologic malignancy including:\n\n   Group 1:\n\n   Group 1a\n   * Relapsed or refractory low risk tumor lysis CLL\u002FSLL subjects (ALC \\\u003C 25 x 109 cells\u002FL and all lymph nodes \\\u003C 5 cm) who have received at least two prior therapies. Subjects may also have slowly progressed on irreversible BTK inhibitors while on treatment with these agents.\n   * For CLL\u002FSLL subjects who come off BCR antagonist treatment (BTK inhibitors, P13K inhibitors, etc.) allows washout for 2 days as these subjects, progress quickly after treatment discontinuation and then remain eligible (steroids may be given during these two days to allow disease control).\n\n   Group 1b\n   * Morphologically confirmed diagnosis of MF in accordance with the WHO 2016 revised criteria, that is relapsed, intolerant, and\u002For refractory and that, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits;\n   * Morphologically confirmed diagnosis of MDS\u002FMPN, excluding juvenile myelomonocytic leukemia (JMML), in accordance with WHO 2016 revised criteria, that is relapsed and\u002For refractory and that, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits;\n   * Chronic myelomonocytic leukemia (CMML) with \\\u003C9% blasts;\n   * Or atypical chronic myeloid leukemia (aCML) with Hgb \\> 10g\u002FdL, WBC count \\\u003C 50 x 109 cells\u002FL, \\\u003C10% immature circulating cells;\n   * Or MDS\u002FMPN with ring sideroblasts and thrombocytosis (MDS\u002FMPN-RS-T) with Hgb \\> 10g\u002FdL;\n   * Or myelodysplastic\u002Fmyeloproliferative neoplasm, unclassifiable (MDS\u002FMPN-UC)\n   * CMML-2 with 10-19% blasts as defined by WHO 2016 revised criteria that is relapsed and\u002For refractory to prior HMA therapy;\n   * Relapsed and\u002For refractory MPN-BP as defined by WHO 2016 revised criteria that is transformed MPN with \\>20% myeloid blasts in the peripheral blood or bone marrow, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits;\n   * MDS subjects with refractory anemia with excess blasts (MDS-EB; subtype MDS-EB-1 or MDS-EB-2) as defined by WHO 2016 revised criteria and\u002For MDS with high- or very high-risk (risk score \\> 4.5) per the Revised International Prognostic Scoring System (IPSS-R, refer to Appendix 11; Section 15.13) who have no available therapies known to provide clinical benefit;\n   * Relapsed or refractory AML subjects (including de novo AML, secondary AML evolving from MDS or MPN or other antecedent hematologic disorder, and therapy-related AML) as defined by WHO 2016 revised criteria, subjects who have no available therapies known to provide clinical benefits; subjects with prior BCL-2 inhibitor therapy are permitted. WBC needs to be ≤ 25 × 109 cells\u002FL at the time of initiating investigational therapy (hydroxyurea is allowed to control WBC prior to and during therapy).\n\n   Group 1c\n   * Relapsed or refractory low risk tumor lysis NHL (NHL histologies \\[MZL, FL, WM, DLBCL, ATLL, PTCL, AITL, ALCL, MCL\\] are to be included per the 2016 World Health Organization \\[WHO\\] criteria) subjects, must have histologically documented diagnosis of a non-Hodgkin lymphoma as defined in the WHO classification scheme. Subjects have received at least 2 prior therapies and have no available therapies known to provide clinical benefit; For subjects with indolent NHL (Grade 1\\~3a FL, MZL) who have received two prior systemic therapies and have relapsed or progressed according to 2014 Lugano;\n   * Low risk tumor lysis transformed follicular, MZL, WM (to large cell or aggressive lymphoma) subjects who must have received at least one prior systemic therapy for the transformed lymphoma (unless combination chemotherapy is not appropriate);\n   * Low risk tumor lysis Richter transformation (RT): previously treated CLL and biopsy-proven Richter transformation with DLBCL histology after receiving at least one regimen for RT;\n   * Relapsed or refractory multiple myeloma (MM) subjects who have received a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 and have no treatment options available known to provide clinical benefit;\n   * Low risk tumor lysis T-cell prolymphocytic leukemia (T-PLL) subjects who have received one therapy for this and are relapsed or refractory;\n\n   Group 1d\n   * Relapsed or refractory ALL with dexamethasone run-in \\[5 days, dexamethasone 10mg\u002Fm2 (divided BID)\\];\n   * Or r\u002Fr ALL in remission but with detectable MRD (MRD +) by any detection method per institution standard of practice;\n   * IT chemo (per institutional SOC) is permitted prior to LP-118 C1D1 dosing, and then concomitantly on treatment if in best interest of the subject;\n   * Relapsed or refractory ALL subjects with B cell phenotype who have received at least two prior therapeutic regimens (such as multi-agent chemotherapy and\u002For tyrosine kinase inhibitors including bosutinib, dasatinib, imatinib, nilotinib or ponatinib) and failed, or are currently ineligible\u002Fintolerant for CD19-based target therapy (e.g. Blinatumomab); Relapsed or refractory ALL subjects with T cell phenotype who have received at least one prior therapy and failed.\n   * Relapsed or refractory ALL subjects with age between 13 - 18 years and have body weight ≥ 40kg, ALL subjects with B cell phenotype who have received at least two prior therapeutic regimens (such as multi-agent chemotherapy and\u002For tyrosine kinase inhibitors including bosutinib, dasatinib, imatinib, nilotinib or ponatinib) and progressed, or are currently ineligible\u002Fintolerant for CD19-based target therapy (e.g. Blinatumomab); Relapsed or refractory ALL subjects with T cell phenotype who have received at least one prior therapy and progressed.\n\n   Group 2\n   * Relapsed or refractory intermediate and high risk tumor lysis CLL\u002FSLL subjects who have received at least two prior therapies;\n   * Relapsed or refractory intermediate and high risk tumor lysis NHL (NHL histologies \\[MZL, FL, WM, DLBCL, ATLL, PTCL, AITL, ALCL, MCL\\] are to be included per the 2016 World Health Organization \\[WHO\\] criteria) subjects, must have histologically documented diagnosis of a non-Hodgkin lymphoma as defined in the WHO classification scheme. Subjects have received at least 2 prior therapies and have no available therapies known to provide clinical benefit; For subjects with indolent NHL (Grade 1\\~3a FL, MZL) who have received two prior systemic therapies and have relapsed or progressed according to 2014 Lugano;\n   * Intermediate and high risk tumor lysis transformed follicular, MZL, WM (to large cell or aggressive lymphoma) subjects who must have received at least one prior systemic therapy for the transformed lymphoma (unless combination chemotherapy is not appropriate);\n   * Intermediate and high risk tumor lysis Richter transformation (RT): previously treated CLL and biopsy-proven Richter transformation with DLBCL histology after receiving at least one regimen for RT;\n   * Intermediate and high risk tumor lysis T-cell prolymphocytic leukemia (T-PLL) subjects who have received one therapy for this and are relapsed or refractory;\n3. For Group 1d ALL subjects only, white blood cell (WBC) count ≤ 25 × 109 cells\u002FL at the time of enrollment (glucocorticoids or hydroxyurea is permitted to control WBC count prior to and during therapy).\n4. Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2.\n5. Adequate cardiac function defined as shortening fraction of ≥ 40% by 2D echocardiogram without Doppler.\n6. Subject must have adequate bone marrow (independent of growth factor support), coagulation, renal, and hepatic function, per laboratory reference ranges at Screening as follows:\n\n   Bone marrow criteria:\n   * Group 1 (r\u002Fr low risk tumor lysis CLL\u002FSLL (ALC \\\u003C 25 x 109 cells\u002FL and all lymph nodes \\\u003C 5 cm), NHL, RT, MM, T-PLL):\n   * Absolute Neutrophil Count (ANC) ≥ 1 x 109\u002FL (An exception is for subjects with an ANC\\\u003C1 x 109\u002FL and bone marrow heavily infiltrated with underlying disease)\n   * Platelets ≥ 50 x 109\u002FL on day of screening (entry platelet count must be independent of transfusion with 14 days of screening);\n   * Hemostasis criteria: Activated partial thromboplastin time (APPT) and prothrombin time (PT) ≤ 1.5 × the upper limit of normal (ULN);\n   * Renal function criteria: Serum creatinine ≤ ULN (per local institution reference range) or Calculated creatinine clearance (Cr Cl) ≥ 60 mL\u002Fmin using 24-hour CrCl OR by Cockcroft-Gault formula using actual body weight.\n   * Hepatic function criteria: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN; bilirubin ≤ 1.5 × ULN (except subjects with Gilbert's Syndrome, who may have a bilirubin \\> 1.5 × ULN, per discussion between the Investigator and the Medical Monitor).\n7. Females of childbearing potential (i.e., non-postmenopausal for at least 2 years or surgically sterile) and non-sterile males must practice at least 1 of the following methods of birth control with their partner(s) throughout the study and for 90 days after discontinuing study drug:\n\n   * Total abstinence from sexual intercourse as the preferred lifestyle of the subject; periodic abstinence is not acceptable;\n   * Surgically sterile partner(s) by vasectomy, bilateral orchiectomy, bilateral tubal ligation, bilateral oophorectomy or hysterectomy;\n   * Intrauterine device;\n   * Hormonal contraceptives (oral, parenteral, vaginal ring or transdermal) associated with inhibition of ovulation initiated for at least 1 month prior to study drug administration.\n8. Females of childbearing potential must have a negative pregnancy result as follows:\n\n   * At Screening on a serum sample obtained within 7 days prior to the first study drug administration, and\n   * Prior to dosing on a urine or serum sample obtained on the first day of study drug administration if ithas been \\> 7 days since obtaining the serum pregnancy test results in Screening.\n   * If a urine pregnancy test at any timepoint during the study is positive or indeterminate, a serum pregnancy test will be performed for confirmation\n9. Male subjects must refrain from sperm donation, from initial study drug administration until 90 days after the last dose of study drug.\n10. Subject must be able to understand and voluntarily sign and date an informed consent form (ICF), approved by an IRB, prior to any protocol-related procedures.\n\nExclusion Criteria:\n\nA subject will not be eligible for study participation if he\u002Fshe meets any of the following criteria.\n\n1. Subjects who have undergone autologous\u002Fallogeneic hematopoietic stem cell transplantation (HSCT) therapy within 60 days of the first dose of LP-118, or subjects on immunosuppressive therapy post-HSCT at the time of Screening, or currently with clinically significant graft-versus-host disease (GVHD) as per treating physician (Subjects in relapse after allogeneic transplantation must be off treatment with systemic immunosuppressive agents for at least 4 weeks. The use of topical steroids and\u002For up to 20 mg\u002Fday prednisone or equivalent systemic steroids for ongoing GVHD is permitted.\n2. Subject has a history of other malignancies within past 12 months that are active and could result in competing risks. These cases shall be discussed with the Medical Monitor with the exception below.\n\n   * Subject with breast cancer or prostate cancer on endocrine therapy with stable disease;\n   * Continuation of maintenance therapy in patients with adequately treated malignancy\n   * Adequately treated in situ carcinoma of the cervix uteri;\n   * Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;\n   * Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.\n   * Cancer with expected survival of 2 years or more or that will not confound evaluation of LP-118 treatment\n3. Subject has received any of the following therapies within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of LP-118, or has not recovered to ≤ Grade 2 clinically significant AEs of the previous therapy (excluding neuropathy):\n\n   * Any anti-neoplastic therapy including chemotherapy, hormonal therapy, radiotherapy, biologic or immunotherapy, targeted small molecule agents, etc. (corticosteroid therapy \\\u003C 20 mg\u002Fday prednisone equivalent according to institutional guidelines to treat disease associated symptoms are permitted);\n   * For MF subjects who come off JAK2 antagonists, allow washout for 2 days as these subject's progress quickly after treatment discontinuation and remain eligible (steroids may be given during these two days to allow disease control).\n   * Subjects in need of immediate cytoreduction should be excluded.\n   * Any investigational therapy.\n   * Live vaccines\n4. Subject has received the following medications, therapies, or natural products within 7 days prior to the first dose of LP-118:\n\n   * Cytochrome P450, family 3, subfamily A (CYP3A) strong inhibitors (itraconazole, etc.), or substrates (Appendix 19);\n   * Subject has received strong Cytochrome P450, family 3, subfamily A (CYP3A) inducers within 14 days prior to the first dose of LP-118 (Appendix 19);\n   * Grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit;\n   * There is a 28-day washout period required for subjects who have had prior CAR-T treatment if there is no evidence of cytokine release syndrome (CRS) or other adverse events related to the CAR-T treatment, per discussion with the Medical Monitor.\n5. Subject has a significant history of renal, neurologic, psychiatric, pulmonary, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that, in the opinion of the Investigator, would adversely affect his\u002Fher participation in this study. Any other medical or social condition deemed by the investigator to be likely to interfere with a subject's ability to participate in the study, place the subject at unacceptable risk or interfere with the interpretation of the results. For subjects who have required surgical intervention for any above diseases within the past 6 months, a discussion with the Investigator and the Medical Monitor is needed.\n6. Subject has baseline prolongation of the heart rate-corrected QT (QTcF) interval ≥ 480 ms (calculated per Fridericia's formula \\[QTcF = QT\u002FRR (1\u002F3)\\])), a cardiovascular disability status of New York Heart Association Class ≥ 2 or associated other significant screening ECG or ultrasonic cardiogram abnormalities, per Investigator's judgement. For any subject with underlying RBBB or LBBB, cardiology review is needed to correct QTcF calculation using Sponsor recommended formula.\n7. Subject has significant a history of congenital long QT syndrome or Torsades de Pointes (TdP), uncontrolled or symptomatic arrhythmias, congestive heart failure, myocardial infarction, stroke, or intracranial hemorrhage within 6 months prior to the first dose of LP-118.\n8. Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to:\n\n   * Uncontrolled active systemic infection (bacterial, fungal, viral);\n   * Known poorly controlled human immunodeficiency virus (HIV) or active hepatitis B or C infection (active hepatitis B defined as HbsAg positive, or HbcAb positive with detectable HBV DNA load; active hepatitis C defined as HCV antibody positive with HCV RNA positive);\n   * Unexplained fever \\> 38.5°C within 7 days prior to the first dose of study drug administration (at the discretion of the Investigator if the fever is considered attributed to the subject's malignancy or an explained infection may be enrolled).\n9. A female subject is pregnant or breast-feeding.\n10. Subject incapacity to swallow oral medications, with any malabsorption condition, known dysphagia, short-gut syndrome, gastroparesis, or other conditions that, in the opinion of the Investigator, may limit the ingestion or gastrointestinal absorption, distribution, metabolism and excretion of drugs administered orally.\n11. Subjects with known and active central nervous system (CNS) involvement at Screening.\n12. Subjects with known hypersensitivity to any of the components of LP-118 (see Investigators Brochure for a list of components).\n13. Subjects who are taking QT-prolonging drugs that are known to cause Torsades de Pointes (TdP) (See Appendix 17 for the list of medications that are associated with TdP). In the event a prohibited medication might cause TdP, the PI must first determine if the risk to benefit is in favor of the subject and then discuss with the Medical Monitor about that particular medication on a case-by-case basis.\n14. Major surgery within 14 days prior to the first dose of study drug.","13 Years",{"count":611,"type":21},100,[180],"This is a Phase 1, multi-center, open-label study with a dose-escalation phase (Phase 1a) and a cohort expansion phase (Phase 1b), to evaluate the safety, tolerability, and PK profile of LP-118 under a once daily oral dosing schedule in up to 100 subjects.",[615,616,251,617,237,618,619,620,241,27,28,621,622],"Non Hodgkin Lymphoma","Richter Transformation","T-cell-prolymphocytic Leukemia","Acute Lymphocytic Leukemia","Myeodysplastic Syndrome","Myelodysplastic\u002FMyeloproliferative Neoplasm","Chronic Myelomonocytic Leukemia-2","Myelodysplastic Neoplasm in Blast Phase",[624,625,626],"Hematological Malignancies","Relapsed","Refractory","2026-04-29",{"date":593,"type":33},{"date":630,"type":33},"2022-05-08",{"date":60,"type":21},{"name":633,"class":142},"Newave Pharmaceutical Inc",{"id":635,"slug":636,"hasResults":12,"nctId":637,"briefTitle":638,"officialTitle":639,"acronym":4,"eligibilityCriteria":640,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":641,"targetDuration":4,"studyType":22,"phases":643,"briefSummary":644,"conditions":645,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":652,"lastUpdatePostDateStruct":653,"startDateStruct":655,"completionDateStruct":657,"leadSponsor":659,"locationsCount":64},"100580573","phase-2-sonrotoclax-rituximab-and-zanubrutinib-in-treating-participants-with-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma-and-mantle-cell-lymphoma-100580573","NCT06839053","Sonrotoclax, Rituximab, and Zanubrutinib in Treating Participants With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphoma","SONIC: Escalated Inpatient Ramp-Up of Sonrotoclax in Patients With Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), and Mantle Cell Lymphoma (MCL) (SONIC Study)","Inclusion Criteria:\n\n* Provision of signed and dated written informed consent prior to any study-specific procedures, sampling, or analyses\n* Age 18 years or older\n* Confirmed diagnosis (per World Health Organization \\[WHO\\] guidelines, unless otherwise noted) of one of the following:\n\n  * CLL\u002FSLL COHORT: CLL\u002FSLL diagnosis that meets the International Workshop on Chronic Lymphocytic Leukemia criteria:\n\n    * Meeting the following sets of prior treatment criteria:\n\n      * For the R\u002FR cohort, disease that relapsed after, or was refractory to, at least 1 prior therapy\n      * For the treatment-naïve cohort, patients should have no prior treatment for CLL\u002FSLL (other than 1 aborted regimen \\\u003C 2 weeks in duration and \\> 4 weeks before enrollment)\n    * Requiring treatment per International Workshop on CLL (iwCLL) criteria\n  * MCL COHORT: WHO-defined MCL\n\n    * R\u002FR MCL is defined as a disease that relapsed after, or was refractory to, at least 1 prior systemic therapy\n* Measurable disease, defined as:\n\n  * CLL\u002FSLL: at least 1 lymph node \\> 1.5 cm in longest diameter and measurable in 2 perpendicular dimensions by computed tomography (CT)\u002Fmagnetic resonance imaging (MRI) or clonal lymphocytes \\>= 5 x 109\u002FL present on peripheral blood flow cytometry\n  * MCL, or SLL: at least 1 lymph node \\> 1.5 cm in the longest diameter OR 1 extranodal lesion \\> 1.0 cm in the longest diameter, measurable in 2 perpendicular dimensions by CT\u002FMRI\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2\n* Absolute neutrophil count (ANC) \\>= 1.0 x 10\\^9\u002FL =\\\u003C 7 days before the first dose of the study drug with or without growth factor support. There is an exception for patients with bone marrow involvement, in which case ANC must be \\>= 0.75 x 10\\^9\u002FL before the first dose of the study drug\n* Platelets \\> 75,000 x 10\\^9\u002FL (\\> 75,000 cells\u002Fmm\\^3) =\\\u003C 7 days before the first dose of the study drug without the use of growth factor support or platelet transfusions. Patients with bone marrow involvement will be allowed to have a platelet count \\> 50,000 x 10\\^9\u002FL (\\> 50,000 cells\u002Fmm\\^3) =\\\u003C 7 days before the first dose of the study drug without the use of growth factor support or platelet transfusions\n* Hemoglobin \\> 75 g\u002FL =\\\u003C 7 days before the first dose of the study drug (with or without transfusion)\n* Creatinine clearance or glomerular filtration rate (GFR) \\>= 50 mL\u002Fmin as estimated by one of the following:\n\n  * Cockcroft-Gault equation\n  * Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation\n  * 24-hour urine collection\n* Aspartate aminotransferase (AST)\u002Fserum glutamic-oxaloacetic transaminase =\\\u003C 2 x upper limit of normal (ULN)\n* Alanine aminotransferase (ALT)\u002Fserum glutamic-pyruvic transaminase =\\\u003C 2 x ULN\n* Total bilirubin level =\\\u003C 1.5 x ULN (unless documented Gilbert's syndrome). For patients with documented Gilbert's syndrome, total bilirubin may exceed this value, but direct bilirubin must be =\\\u003C 1.0 x ULN\n* Serum amylase =\\\u003C 1.5 x ULN\n* Serum lipase =\\\u003C 1.5 x ULN\n* Women of childbearing potential (WOCBP) must have a negative serum pregnancy test =\\\u003C 7 days before the first dose of the study drug. In addition, they must use a highly effective method of birth control initiated before the first dose of the study drug, for the duration of the study treatment period, and for \\>= 180 days after the last dose of the study drug\n\n  * NOTE: WOCBP is a woman who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months)\n  * NOTE: Highly effective contraceptive methods include the following:\n\n    * Combined (estrogen and progestogen-containing) hormonal contraception associated with the inhibition of ovulation. Combined hormonal contraception may be oral, intravaginal, or transdermal\n\n      * Progestogen-only hormonal contraception associated with the inhibition of ovulation. Progesterone-only hormonal contraception may be oral, injectable, or implantable\n      * An intrauterine device\n      * Intrauterine hormone-releasing system\n      * Bilateral tubal\n    * Vasectomized partner\n\n      * Sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment, starting the day before the first dose of study treatment, for the duration of the study, and for \\>= 180 days after the last dose of study drug. Total sexual abstinence should only be used as a contraceptive method if it is in line with the patients' usual and preferred lifestyle. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to investigational medicinal product, and withdrawal are not acceptable methods of contraception\n  * Of note, barrier contraception (including male and female condoms with or without spermicide) is not considered a highly effective method of contraception, and, if used, this method must be used in combination with another acceptable method listed above\n  * For patients using hormonal contraceptives such as birth control pills or devices, a second barrier method of contraception (e.g., condoms) must be used\n* Nonsterile men must use a highly effective method of birth control along with barrier contraception for the duration of the study treatment period and for ≥ 180 days after the last dose of the study drug. During this same period, they must not donate sperm. Sterile men must use barrier contraception\n* Life expectancy of \\> 6 months\n* Able to comply with the requirements of the study\n\nExclusion Criteria:\n\n* Exposure to a Bcl-2 inhibitor within the last 12 months or a history of disease progression while taking a Bcl-2 inhibitor\n* Prior malignancy (other than the disease under study) within the past 2 years, except for curatively treated basal or squamous skin cancer, melanoma, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score =\\\u003C 6 prostate cancer\n* Underlying medical conditions that may render the administration of study drug hazardous or obscure the interpretation of safety or efficacy results\n* Known current central nervous system involvement by lymphoma\u002Fleukemia\n* Known plasma cell neoplasm other than a monoclonal gammopathy of undetermined significance (MGUS), prolymphocytic leukemia, or history of or currently suspected Richter's syndrome\n* Prior autologous stem cell transplant unless \\>= 3 months after transplant; or prior chimeric antigen receptor T-cell (CAR-T) therapy unless \\>= 3 months after cell infusion\n* Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD), or requiring immunosuppressive drugs for the treatment of GVHD, or have taken calcineurin inhibitors within 4 weeks prior to consent\n* History of a severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention\n* Use of the following substances prior to the first dose of the study drug:\n\n  * =\\\u003C 28 days before the first dose of the study drug:\n\n    * Any biologic and\u002For immunologic-based therapy(ies) including experimental therapy(ies) for leukemia, lymphoma, or myeloma (including, but not limited to, monoclonal antibody therapy, e.g., rituximab, and\u002For cancer vaccine therapy). If biological and\u002For immunologic-based therapy(ies) are used for non-oncological indications, enrollment will be at the discretion of the principal investigator (PI)\n  * =\\\u003C 14 days before the first dose of the study drug:\n\n    * Systemic chemotherapy or radiation therapy\n  * =\\\u003C 7 days before the first dose of the study drug:\n\n    * Corticosteroid given with antineoplastic intent\n  * =\\\u003C 3 days (or 5 half-lives; whichever is shorter) before the first dose of the study drug:\n\n    * Bruton's tyrosine kinase inhibitor (BTKi) or other small molecule inhibitor is given with antineoplastic intent\n* Active fungal, bacterial, and\u002For viral infection requiring systemic therapy\n\n  * Note: oral antibiotics for minor bacterial infections are allowed\n* Major surgery =\\\u003C 4 weeks before the first dose of study treatment\n* Toxicity from prior anticancer therapy that has not recovered to grade =\\\u003C 1 (except for alopecia, ANC, and platelet count; for ANC and platelet count)\n* Clinically significant cardiovascular disease including the following:\n\n  * Myocardial infarction =\\\u003C 6 months before screening\n  * Unstable angina =\\\u003C 3 months before screening\n  * New York Heart Association class III or IV congestive heart failure\n  * History of clinically significant arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes)\n  * Heart rate-corrected QT interval \\> 480 milliseconds based on Fridericia's formula\n  * History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place\n  * Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements, at screening, showing systolic blood pressure \\> 170 mmHg and diastolic blood pressure \\> 105 mmHg\n* Known infection with human immunodeficiency virus (HIV) or serologic status reflecting active viral hepatitis B (HBV) or viral hepatitis C (HCV) infection as follows:\n\n  * Presence of viral hepatitis B surface antigen (HBsAg) or viral hepatitis B core antibody (HBcAb)\n\n    * Note: Patients with the presence of HBcAb, but absence of HBsAg, are eligible if HBV deoxyribonucleic acid (DNA) is undetectable and if they are willing to take HBV reactivation prophylaxis and undergo monitoring for HBV reactivation\n  * Presence of HCV antibody\n\n    * Note: Patients with the presence of HCV antibody are eligible if HCV ribonucleic acid (RNA) is undetectable and if they are willing to undergo monitoring for HCV reactivation\n* Pregnant or lactating women\n* Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedure, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction\n* Inability to comply with study procedures\n* Receiving any treatment with a strong or moderate CYP3A4 inhibitor =\\\u003C 14 days (or 5 half-lives, whichever is longer) before the first dose of sonrotoclax\n* Unwillingness to stop consumption of grapefruit, grapefruit products, Seville oranges, or starfruit within 3 days before the first dose of sonrotoclax or during the study\n* Receiving any treatment with a strong CYP3A4 inducer =\\\u003C 14 days (or 5 half-lives, whichever is longer) before first dose of sonrotoclax\n* History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases, including but not limited to pulmonary fibrosis and acute lung diseases\n* Autoimmune anemia and\u002For thrombocytopenia that is poorly controlled by corticosteroids or other standard therapy\n* Ongoing, drug-induced liver injury, alcoholic liver disease, nonalcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension\n* Receiving drugs known to prolong the QT\u002Fcorrected QT (QTc) interval\n* Vaccination with a live vaccine =\\\u003C 35 days before the first dose of the study drug\n\n  * Note: Seasonal vaccines for influenza are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed",{"count":642,"type":21},30,[51],"This phase II trial studies the side effects of an escalated ramp-up of sonrotoclax following initial debulking with zanubrutinib or rituximab in treating patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL) that is newly diagnosed, has come back after a period of improvement (relapsed) or does not respond to treatment (refractory). Rituximab is a monoclonal antibody that binds to a protein called CD20, which is found on B-cells, and may kill tumor cells. Zanubrutinib may stop the growth of tumor cells by blocking a protein called Bruton's tyrosine kinase (BTK), which is needed for tumor cell growth. Sonrotoclax works by blocking a protein called B-cell lymphoma-2 (BCL-2). This protein helps certain types of blood tumor cells to survive and grow. When sonrotoclax blocks Bcl-2 it slows down or stops the growth of tumor cells and helps them die. Giving an increased dose of sonrotoclax over a shorter period of time in combination with zanubrutinib or rituximab may be safe and tolerable in treating patients with newly diagnosed, relapsed or refractory CLL, SLL, and MCL.",[27,311,646,647,648,649,650,651,28],"Recurrent Chronic Lymphocytic Leukemia","Recurrent Mantle Cell Lymphoma","Recurrent Small Lymphocytic Lymphoma","Refractory Chronic Lymphocytic Leukemia","Refractory Mantle Cell Lymphoma","Refractory Small Lymphocytic Lymphoma","2026-04-17",{"date":654,"type":33},"2026-04-22",{"date":656,"type":33},"2025-06-02",{"date":658,"type":21},"2032-07-01",{"name":660,"class":63},"Fred Hutchinson Cancer Center",{"id":662,"slug":663,"hasResults":12,"nctId":664,"briefTitle":665,"officialTitle":666,"acronym":4,"eligibilityCriteria":667,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":668,"targetDuration":4,"studyType":22,"phases":669,"briefSummary":670,"conditions":671,"keywords":672,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":673,"lastUpdatePostDateStruct":674,"startDateStruct":676,"completionDateStruct":678,"leadSponsor":680,"locationsCount":222},"100405510","phase-2-venetoclax-obinutuzumab---acalabrutinib-in-rr-cll-100405510","NCT04560322","Venetoclax-Obinutuzumab +\u002F- Acalabrutinib in R\u002FR CLL","A Phase 2 Study of MRD Adapted Therapy With Venetoclax-obinutuzumab in Patients With High or Intermediate BALL Risk Relapsed or Refractory CLL, With Addition of Acalabrutinib in Patients Who Fail to Achieve MRD Eradication","Inclusion Criteria:\n\n* Diagnosis of CLL or SLL according to WHO criteria\n* Participants must require therapy according to iwCLL 2018 guidelines\n* Participants must have ≥ 2 points (high or intermediate risk disease) according to the CLL\n\nBALL Risk Model:\n\n* Beta-2 microglobulin If ≥ 5 mg\u002FL, assign 1 point\n* Lactate dehydrogenase If \\>institutional upper limit of normal, assign 1 point\n* Hemoglobin If \\\u003C11 g\u002FdL (female) or \\\u003C12 g\u002FdL (male), assign 1 point\n* Time from start of last therapy If \\\u003C24 months, assign 1 point, If 4 points, patient is high risk, If 2-3 points, patient is intermediate risk, If 0-1 points, patient is low risk\n\n  * Participants must have received prior systemic therapy for CLL\n  * Age over 18 years\n  * ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)\n  * Participants must have adequate organ function as defined below:\n* total bilirubin ≤2 × institutional upper limit of normal unless considered secondary to Gilbert's syndrome, in which case ≤3 x ULN\n* AST(SGOT)\u002FALT(SGPT) ≤2 × institutional upper limit of normal\n* creatinine within normal institutional limits OR\n* creatinine clearance ≥30 mL\u002Fmin according to the Cockcroft-Gault Equation for participants with creatinine levels above institutional normal.\n\n  * Participants must have adequate marrow function as defined below (unless clearly due to disease under study per investigator discretion)\n* absolute neutrophil count ≥1,000\u002FmcL\n* platelets ≥75,000\u002FmcL OR\n* \\> 20,000\u002FmcL if thrombocytopenia is clearly due to disease under study (per investigator discretion).\n\n  * For females of childbearing potential, a negative serum pregnancy test within 7 days of study treatment\n  * For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and\u002For partner) to use highly effective form(s) of contraception (i.e., one that results in a low failure rate \\[\\\u003C1% per year\\] when used consistently and correctly) and to continue its use for 90 days after the last dose of acalabrutinib or venetoclax AND for 18 months after the last dose of obinutuzumab (whichever date is later)\n  * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.\n  * Willingness to not donate sperm or oocytes during the entire study treatment period and after treatment discontinuation\n  * Ability to understand and the willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\n* Prior therapy with a BTK inhibitor (e.g. acalabrutinib) or BCL2 inhibitor (e.g. venetoclax), with the following exception:\n* Patients with undetectable MRD by flow cytometry at 10 (peripheral blood or bone marrow) or CR from prior treatment with BCL2 inhibitor (with or without BTK inhibitor) are eligible. Note: Patients who received prior BTK inhibitor therapy alone are not eligible.\n* Known hypersensitivity (IgE-mediated) reaction to obinutuzumab or to any of its excipients\n* Participants who are receiving any other investigational agents unless authorized by the overall study principal investigator\n* Known active histological transformation from CLL to an aggressive lymphoma (i.e., Richter's transformation)\n* Active malignancy or systemic therapy for another malignancy within 3 years; local\u002Fregional therapy with curative intent such as surgical resection or localized radiation within 3 years of treatment is permitted; active prostate cancer that is considered low-risk and appropriate for continued active surveillance strategy is permitted.\n* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 2 weeks prior to Cycle 1, Day 1\n* Known bleeding diathesis\n* Pregnant women are excluded from this study because the study agents have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study agents, breastfeeding should be discontinued if the mother is treated with study therapy.\n* Prior major surgical procedure within 4 weeks of study, or anticipation of need for a major surgical procedure during the course of the study\n* Known CNS hemorrhage or stroke within 6 months of the study\n* History of progressive multifocal leukoencephalopathy (PML)\n* History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C infection\n\n  * Patients with occult or prior HBV infection (defined as positive total hepatitis B core antibody \\[HBcAb\\] and negative HBsAg) may be included if HBV DNA is undetectable. These patients must be willing to take appropriate anti-viral prophylaxis as indicated and undergo monthly DNA testing.\n  * Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA\n* Congestive heart failure, New York Heart Association classification III\u002FIV\n* Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis\n* Receipt of live-virus vaccines within 28 days prior to the initiation of study treatment or need for live-virus vaccines at any time during study treatment\n* Known condition or other clinical situation that would affect oral absorption\n* Psychiatric illness\u002Fsocial situations that would interfere with study compliance\n* Receipt of therapy with strong inhibitors or inducers of CYP3A, CYP2C8, CYP2C9 and CYP2C19, within 7 days prior to the first dose of study drug administration\n* Consumption of grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of study drug administration.\n* Requires dual antiplatelet therapy or anticoagulation with warfarin",{"count":72,"type":21},[51],"This research study is studying a combination of drugs as a possible treatment for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).\n\nThe names of the study drugs involved in this study are:\n\n* obinutuzumab\n* venetoclax\n* acalabrutinib",[27,28],[27,28],"2026-04-09",{"date":675,"type":33},"2026-04-13",{"date":677,"type":33},"2020-10-19",{"date":679,"type":21},"2029-03-01",{"name":681,"class":63},"Massachusetts General Hospital"]