[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"refractory-transformed-chronic-lymphocytic-leukemia\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:refractory-transformed-chronic-lymphocytic-leukemia":33},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,7,0,[8,47,84,114,140,169,196],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":35,"lastUpdatePostDateStruct":36,"startDateStruct":39,"completionDateStruct":41,"leadSponsor":43,"locationsCount":46},"100430991","phase-1-cd19-directed-car-t-cell-therapy-for-the-treatment-of-relapsedrefractory-b-cell-malignancies-100430991",false,"NCT04892277","CD19-Directed CAR-T Cell Therapy for the Treatment of Relapsed\u002FRefractory B Cell Malignancies","Phase I Dose Escalation Trial of CD19 Directed Chimeric Antigen Receptor T Cell Therapy in the Treatment of Relapsed\u002FRefractory B Cell Malignancies","Inclusion Criteria:\n\n* Age \\>= 18 years\n* Relapsed or refractory CD19+ B cell malignancies of the one of the following histopathology:\n\n  * Biopsy proven B-cell non-Hodgkin lymphoma (NHL) of any histopathology (including Richter Transformation of CLL); relapsed or refractory disease defined as:\n\n    * Two or more prior lines of therapy, at least one anthracycline containing regimen, unless intolerable. Exception: Patients with Richter transformation of CLL are eligible if they had \\>= one prior treatment, including prior BTK inhibition\n    * Demonstration of progressive or stable disease by positron emission tomography\u002Fcomputed tomography (PET\u002FCT) or CT criteria as the best response to the most recent chemotherapy regimen according to the revised Lugano Response Criteria for Malignant Lymphoma.\n    * Measurable disease defined as measurable by CT portion of a PET\u002FCT: To be considered measurable, the must be at least one lesion that has a single diameter of (\\>1.5 cm Note: Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy\n  * Biopsy proven SLL or flow cytometry proven CLL; relapsed disease defined as:\n\n    * \\>= two prior lines of therapy, and\u002For \\>= 6 months of second line prior BTK inhibition (e.g. venetoclax and ibrutinib). Exception: Patients in stable disease (SD) or partial response (PR) with a known ibrutinib resistance mutation (BTK or phospholipase Cgamma2) may be included even if on ibrutinib therapy for less than 6 months.\n    * Demonstration of progressive or stable disease by PET\u002FCT or CT criteria according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL2018) criteria\n    * Measurable disease by CT portion of a PET\u002FCT where at least one lesion has a single diameter of \\>1.5 cm or peripheral blood absolute blood lymphocyte count (ALC) of \\> 5000. Note: Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1\n* Hemoglobin \\>= 8.0 g\u002FdL (=\\\u003C 14 days prior to registration)\n* Absolute neutrophil count (ANC) \\>= 500\u002Fmm\\^3 (=\\\u003C 14 days prior to registration)\n* Platelet count \\>= 30,000\u002Fmm\\^3 (=\\\u003C 14 days prior to registration)\n* Total bilirubin =\\\u003C 2.0 mg\u002FdL (with the exception of subjects with Gilbert's syndrome. Subjects with Gilbert's syndrome may be included if their total bilirubin is =\\\u003C 3.0 x upper limit of normal (ULN) and direct bilirubin =\\\u003C 1.5 x ULN) (=\\\u003C 14 days prior to registration)\n* Alanine aminotransferase (ALT) and aspartate transaminase (AST) =\\\u003C 3 x ULN (=\\\u003C 14 days prior to registration)\n* Prothrombin time (PT) \u002F international normalized ratio (INR) and\u002For activated partial thromboplastin time (aPTT) =\\\u003C 1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy (for patients receiving anticoagulation, there should be no prior history of bleeding, and no recent deep venous thrombosis\u002Fpulmonary embolism (DVT\u002FPE) within the last 6 months of enrollment) (=\\\u003C 14 days prior to registration)\n* Calculated creatinine clearance \\>= 45 ml\u002Fmin using the Cockcroft-Gault formula (=\\\u003C 14 days prior to registration)\n* Cardiac ejection fraction \\>= 50% and no evidence of clinically significant pericardial effusion as determined by an echocardiogram (ECHO) or multigated acquisition scan (MUGA) scan\n* Baseline oxygen saturation \\>= 92% on room air\n* Negative serum pregnancy test done =\\\u003C 7 days prior to registration, for persons of childbearing potential only\n* Women patients of child bearing potential, including women with tubal ligations, must commit to using use 2 highly effective forms of birth control (defined as the use of an intrauterine device, a barrier method with spermicide, condoms, any form of hormonal contraceptives) for the duration of the study and for 12 months following IC19\u002F1563 therapy\n* Provide written informed consent\n* Willingness to provide mandatory blood specimens for correlative research\n* Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)\n\nExclusion Criteria:\n\n* Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:\n\n  * Pregnant persons\n  * Nursing persons\n  * Women of childbearing potential who are unwilling to employ highly effective contraception\n* Sexually active males who are not willing to use contraception during the study and for \\>= 12 months after IC19\u002F1563 therapy\n* Patients who are able to obtain market approved CD19 CAR T-cell therapies\n* Live vaccine =\\\u003C 6 weeks prior to start of registration\n* Autologous stem cell transplant =\\\u003C 6 weeks of registration\n* History of allogenic stem cell transplant if was performed less than 100 days prior to registration, if patients have active graft-versus host disease (GVHD) or are if patients are on chronic immunosuppression. Patients with allogeneic transplantation more than 100 days prior to registration, with no active GVHD and who are not on immunosuppression are eligible\n* History of a seizure disorder, cerebrovascular ischemia\u002Fhemorrhage, dementia, cerebellar disease, or any autoimmune disease with central nervous system (CNS) involvement\n* Any form of primary immunodeficiency such as severe combined immunodeficiency disease\n* Current need of systemic corticosteroid therapy, in doses over 20 mg \u002Fday of prednisone or equivalent forms of steroids\n* History of severe immediate hypersensitivity reaction to CART19, stem cell infusion dimethyl sulfoxide (DMSO) or any of the CAR-T cryopreservation ingredients\n* History of malignancy other than non-melanoma skin cancer, carcinoma in situ (e.g. cervix, bladder, breast) or early stage cancers (Stage I or II), unless disease free for \\>= 2 years\n* Clinically significant active infection (e.g. simple urinary tract infection \\[UTI\\], bacterial pharyngitis allowed) or currently receiving IV antibiotics or have received IV antibiotics =\\\u003C 7 days prior to registration. Note: prophylactic antibiotics, antivirals and antifungals are permitted\n* Known history of human immunodeficiency virus (HIV) infection or acute or chronic hepatitis B or hepatitis C infection. Subjects with a history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines. Prophylactic antiviral therapy should be considered per institutional guidelines\n* History of any of the following cardiovascular conditions =\\\u003C 6 months:\n\n  * Class III or IV heart failure as defined by the New York Heart Association (NYHA)\n  * Cardiac angioplasty or stenting\n  * Myocardial infarction\n  * Unstable angina\n  * Or other clinically significant cardiac disease\n* Any other acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or investigational product administration or that, in the judgment of the investigator, would make the subject inappropriate for entry into the study\n* Concurrent cancer therapy. The following are exceptions:\n\n  * Treatment with therapies may continue at time of registration; however, the washout period must be met prior to leukapheresis\n  * Treatment with any other investigational agent may continue at time of registration provided last date of treatment is =\\\u003C 14 days prior to leukapheresis.","ALL","18 Years",{"count":19,"type":20},25,"ESTIMATED","INTERVENTIONAL",[23],"PHASE1","This phase I trial studies the effects of CD-19 directed chimeric antigen receptor (CAR)-T cell therapy for the treatment of patients with B cell malignancies that have come back (recurrent) or have not responded to treatment (refractory). CD-19 CAR-T cells use some of a patient's own immune cells, called T cells, to kill cancer. T cells fight infections and, in some cases, can also kill cancer cells. Some T cells are removed from the blood, and then laboratory, researchers will put a new gene into the T cells. This gene allows the T cells to recognize and possibly treat cancer. The new modified T cells are called the IC19\u002F1563 treatment. IC19\u002F1563 may help treat patients with relapsed\u002Frefractory B cell malignancies.",[26,27,28,29,30,31,32,33],"Recurrent B-Cell Non-Hodgkin Lymphoma","Recurrent Chronic Lymphocytic Leukemia","Recurrent Small Lymphocytic Lymphoma","Recurrent Transformed Chronic Lymphocytic Leukemia","Refractory B-Cell Non-Hodgkin Lymphoma","Refractory Chronic Lymphocytic Leukemia","Refractory Small Lymphocytic Lymphoma","Refractory Transformed Chronic Lymphocytic Leukemia","RECRUITING","2026-06-05",{"date":37,"type":38},"2026-06-09","ACTUAL",{"date":40,"type":38},"2022-10-03",{"date":42,"type":20},"2040-03-27",{"name":44,"class":45},"Mayo Clinic","OTHER",1,{"id":48,"slug":49,"hasResults":11,"nctId":50,"briefTitle":51,"officialTitle":52,"acronym":4,"eligibilityCriteria":53,"healthyVolunteers":11,"sex":16,"minAge":54,"maxAge":4,"enrollmentInfo":55,"targetDuration":4,"studyType":21,"phases":57,"briefSummary":58,"conditions":59,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":74,"lastUpdatePostDateStruct":75,"startDateStruct":77,"completionDateStruct":79,"leadSponsor":81,"locationsCount":83},"100471377","phase-1-genetically-engineered-cells-anti-cd19cd20cd22-car-t-cells-for-the-treatment-of-relapsed-or-refractory-lymphoid-malignancies-100471377","NCT05418088","Genetically Engineered Cells (Anti-CD19\u002FCD20\u002FCD22 CAR T-cells) for the Treatment of Relapsed or Refractory Lymphoid Malignancies","Phase I Clinical Trial of Anti-CD19\u002F20\u002F22 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Lymphoid Malignancies (Non-Hodgkin Lymphoma, Acute Lymphoblastic Leukemia, Chronic Lymphocytic Leukemia, B-Prolymphocytic Leukemia)","Inclusion Criteria:\n\n* Adult subjects with relapsed or refractory non-Hodgkin lymphoma with lesions =\\\u003C 5 cm, indolent lymphomas, chronic lymphocytic leukemia without Richter's transformation, or B-prolymphocytic leukemia (Cohort A)\n* OR adult subjects with lymphoid blast crisis, acute lymphoblastic leukemia, chronic lymphocytic leukemia with Richter's transformation, non-Hodgkin lymphoma with lesions \\> 5 cm and\u002For lymphoblastic lymphoma, or non-Hodgkin lymphoma with circulating lymphoma cells, B-Prolymphocytic leukemia with lesions \\> 5 cm (not including splenomegaly (Cohort B).\n* OR Pediatric subjects with Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma\n* Subjects must have been treated with at least two lines of therapy. Disease must have either progressed after the last regimen or presented failure to achieve complete remission with the last regimen. B-PLL is defined as having greater than 55% prolymphocytes in the peripheral blood\n* Subjects with relapsed\u002Frefractory CLL after at least 2 prior lines of appropriate therapy and must have previously received an approved BTK inhibitor and venetoclax\n* Subjects with refractory high-grade B-cell lymphoma who relapse within 12 months of autologous stem cell transplant\n* Subjects with relapsed\u002Frefractory B-prolymphocytic leukemia who received at least 1- 2 prior lines of appropriate therapy and who have failed or are ineligible for allogeneic stem cell transplant\n* Subjects with relapsed\u002Frefractory acute B-lymphoblastic leukemia who received at least 2 prior lines of appropriate therapy or who have failed or are ineligible for allogeneic stem cell transplant.\n* The patient's lymphoid malignancy must be positive for at least one target antigen (CD19 and\u002For CD20 and\u002For CD22), either by immunohistochemistry or flow cytometry analysis on the last biopsy available or peripheral blood for circulating disease.\n* Patients who received blinatumomab or inotuzumab are eligible.\n* Patients who received prior CAR T-cells are eligible, (commercial CD 19 CAR-T cells or dual CAR-T cells), if it has been at least 30 days since previous CAR T cell therapy and \\\u003C5% of circulating levels of CD3+ cells express the prior CAR by flow cytometry.\n* Age \\>= 2 years\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 2. For patients \\\u003C 16 years, Performance score Lansky \\>= 50\n* Total bilirubin =\\\u003C 1.5 times the institutional upper limit of normal for age\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\]) =\\\u003C 3 X institutional upper limit of normal for age\n* Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \\[SGPT\\]) =\\\u003C 3 X institutional upper limit of normal for age\n* Creatinine clearance more than or equal to 50 ml\u002Fmin calculated by the Cockcroft - Gault formula, or by Schwartz formula for patients \\\u003C 18 years\n* Subjects must have adequate pulmonary function as defined as pulse oximetry \\>= 92% on room air\n* Subjects must have adequate cardiac function as defined as left ventricular ejection fraction \\>= 40% in the most recent echocardiogram\n* Absolute lymphocyte count \\> 100\u002FuL\n* Subjects (or legal guardians) must have the ability to understand and the willingness to sign a written informed consent document\n* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of \\\u003C 1% per year during the treatment period and for at least 6 months after the Anti-CD19\u002F20\u002F22 CAR-T cell infusion\n* A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (\\\u003C 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and\u002For uterus). Examples of contraceptive methods with a failure rate of \\\u003C 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptive s that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices\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* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm\n* With female partners of childbearing potential, men 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 6 months after the Anti-CD19\u002F20\u002F22 CAR-T cell infusion. Men must refrain from donating sperm during this same period\n* With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 6 months after the human anti-CD19 CAR-T cell infusion to avoid potential embryonal or fetal exposure. 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\nExclusion Criteria:\n\n* Autologous transplant within 6 weeks of planned CAR-T cell infusion\n* Allogeneic stem cell transplant or donor lymphocyte infusion within 2 months of planned CAR-T cell infusion and patients must be off immunosuppressive agents. Patients with live vaccines given 28 days prior to lymphodepletion (LD) chemotherapy will be excluded\n* Active graft versus host disease\n* Active central nervous system or meningeal involvement by lymphoma or leukemia. Subjects with untreated brain metastases\u002Fcentral nervous system (CNS) disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of CNS or meningeal involvement must be in a documented remission by CSF evaluation and contrast-enhanced magnetic resonance imaging (MRI) imaging for at least 90 days prior to registration\n* Active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g.cervix, bladder, breast). Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial (e.g.\n\nLow Gleason score prostate Cancer)\n\n* A minimum of 28 days must have elapsed between prior treatment with investigational agent(s) and the day of lymphocyte collection\n* Human immunodeficiency virus (HIV)-seropositive patients are allowable, however must be on effective anti-retroviral therapy with undetectable viral load within 6 months of enrollment to be eligible for this trial\n* Subjects 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\n* 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. Women of childbearing potential must have a negative serum pregnancy test. 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\n* Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy\n* Patients with a positive hepatitis B core antibody or surface antigen are at high risk for hepatitis B virus (HBV) reaction and will require entecavir\u002Ftenofivir prophylaxis or serial hepatitis B (Hep B) PCR monitoring at the direction of an infectious disease specialist. Duration of prophylaxis to correspond with detection of Anti-CD19\u002F20\u002F22 CAR T cells\u002Fviral vector copies in serum or continued evidence of B-cell aplasia such as reduced intravenous immunoglobulin therapy (IVIG) levels. No antiviral prophylaxis is indicated with hepatitis C positivity with negative PCR\n* Patients with history of clinically relevant CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease\n* History of autoimmune disease (i.e. rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months\n* Live vaccines given in 28 days prior to lymphodepleting chemotherapy","2 Years",{"count":56,"type":20},54,[23],"This phase I trial tests the safety, side effects and best infusion dose of genetically engineered cells called anti-CD19\u002FCD20\u002FCD22 chimeric antigen receptor (CAR) T-cells following a short course of chemotherapy with cyclophosphamide and fludarabine in treating patients with lymphoid cancers (malignancies) that have come back (recurrent) or do not respond to treatment (refractory). Lymphoid malignancies eligible for this trial are: non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and B-prolymphocytic leukemia (B-PLL). T-cells (a type of white blood cell) form part of the body's immune system. CAR-T is a type of cell therapy that is used with gene-based therapies. CAR T-cells are made by taking a patient's own T-cells and genetically modifying them with a virus so that they are recognized by a group of proteins called CD19\u002FCD20\u002FCD22 which are found on the surface of cancer cells. Anti-CD19\u002FCD20\u002FCD22 CAR T-cells can recognize CD19\u002FCD20\u002FCD22, bind to the cancer cells and kill them. Giving combination chemotherapy helps prepare the body before CAR T-cell therapy. Giving CAR-T after cyclophosphamide and fludarabine may kill more tumor cells.",[60,61,62,27,63,64,65,29,66,67,68,31,69,70,71,33,72,73],"Recurrent Acute Lymphoblastic Leukemia","Recurrent B Acute Lymphoblastic Leukemia","Recurrent B-Cell Prolymphocytic Leukemia","Recurrent High Grade B-Cell Lymphoma","Recurrent Indolent Non-Hodgkin Lymphoma","Recurrent Non-Hodgkin Lymphoma","Refractory Acute Lymphoblastic Leukemia","Refractory B Acute Lymphoblastic Leukemia","Refractory B-Cell Prolymphocytic Leukemia","Refractory High Grade B-Cell Lymphoma","Refractory Indolent Non-Hodgkin Lymphoma","Refractory Non-Hodgkin Lymphoma","Refactory Childhood Acute Lymphoblastic Leukemia","Refractory Childhood Non-Hodgkin Lymphoma","2026-05-27",{"date":76,"type":38},"2026-05-29",{"date":78,"type":38},"2022-06-30",{"date":80,"type":20},"2027-07-01",{"name":82,"class":45},"Sumithira Vasu",2,{"id":85,"slug":86,"hasResults":11,"nctId":87,"briefTitle":88,"officialTitle":89,"acronym":4,"eligibilityCriteria":90,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":91,"targetDuration":4,"studyType":21,"phases":93,"briefSummary":95,"conditions":96,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":105,"lastUpdatePostDateStruct":106,"startDateStruct":108,"completionDateStruct":110,"leadSponsor":112,"locationsCount":46},"100490909","phase-2-loncastuximab-tesirine-and-mosunetuzumab-for-the-treatment-of-relapsed-or-refractory-diffuse-large-b-cell-lymphoma-100490909","NCT05672251","Loncastuximab Tesirine and Mosunetuzumab for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma","A Phase 2 Study of Loncastuximab Tesirine Plus Mosunetuzumab in Patients With Relapsed\u002FRefractory Diffuse Large B-cell Lymphoma","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* Be willing to provide tissue from a fresh core or excisional biopsy (performed as standard of care) of a tumor lesion prior to starting study therapy or 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) =\\\u003C 2.\n* Histologically confirmed diagnosis of diffuse large B-cell lymphoma or Follicular Lymphoma Grade 3B according to the World Health Organization (WHO) classification, with hematopathology review at the participating institution. Subtypes of DLBCL including transformed indolent lymphomas (TIL) including Richter's Transformation, primary mediastinal large B-cell lymphoma (PMBCL), and high-grade B-cell lymphoma not otherwise specified (HGBCL-NOS) are eligible.\n* Life expectancy \\> 12 months.\n* Histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma Grade 3B according to the WHO classification, with hematopathology review at the participating institution. Subtypes of DLBCL including transformed indolent lymphomas (TIL) including Richter's Transformation, primary mediastinal large B-cell lymphoma (PMBCL), and high-grade B-cell lymphoma not otherwise specified (HGBCL-NOS) are eligible.\n* Relapsed or refractory disease after \\>= 1 prior line of therapy (prior CD19-directed therapy and prior autologous stem cell transplant are allowed).\n\n  * Relapse at the time of study enrollment must have been confirmed histologically (with hematopathology review at the participating institution). Exceptions may be granted with study PI approval.\n* Measurable disease by computerized tomography (CT) or positron emission tomography (PET)\u002FCT scan with one or more sites of disease \\>= 1.5 cm in longest dimension.\n* Tumor must be positive for both CD19 and CD20 by immunohistochemistry after the most recent therapy.\n* Fully recovered from the acute toxic effects (except alopecia) to =\\\u003C Grade 1 to prior anti-cancer therapy\n* Without bone marrow involvement: Absolute neutrophil count (ANC) \\>= 1,000\u002Fmm\\^3.\n\n  * (G-CSF is allowed to reach ANC requirement).\n* With bone marrow involvement: no minimum ANC requirement.\n\n  * (G-CSF is allowed to reach ANC requirement).\n* Platelets \\>= 75,000\u002Fmm\\^3.\n* Total bilirubin =\\\u003C 1.5 X upper limit of normal (ULN).\n\n  * If hepatic involvement by lymphoma, or Gilbert's disease: =\\\u003C 3X ULN.\n* Aspartate aminotransferase (AST) =\\\u003C 2.5 x ULN.\n\n  * If hepatic involvement by lymphoma: AST =\\\u003C 5 x ULN.\n* Alanine aminotransferase (ALT) =\\\u003C 2.5 x ULN.\n\n  * If hepatic involvement by lymphoma: ALT =\\\u003C 5 x ULN .\n* Creatinine clearance of \\>= 40 mL\u002Fmin per 24 hour urine test or the Cockcroft-Gault formula\n* If not receiving anticoagulants: International Normalized Ratio (INR) OR Prothrombin (PT) =\\\u003C 1.5 x ULN.\n* 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) =\\\u003C 1.5 x ULN\n* If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants.\n* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test\n\n  * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.\n* Agreement by females of childbearing potential to abstain from heterosexual intercourse or use two adequate method of birth control, including at least 1 method with a failure rate of \\\u003C 1% per year, for at least 28 days prior to Day 1 of Cycle 1, during the treatment period (including periods of treatment interruption), until 3 months after the final dose mosunetuzumab and 9 months after the last dose of loncastuximab tesirine. Women must refrain from donating eggs during this same period. Agreement by males to abstain from heterosexual intercourse or use a condom with female partners of childbearing potential or pregnant female partners during the treatment period and for 3 months after the final dose of mosunetuzumab and 6 months after the last dose of loncastuximab tesirine. Men must refrain from donating sperm during this same period.\n\n  * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \\> 1 year (women only) with no identified cause other than menopause.\n  * Examples of non-hormonal contraceptive methods with a failure rate of \\\u003C 1% per year include bilateral tubal ligation, male sterilization, established and proper use of progestogen only hormonal contraceptives that inhibit ovulation, hormone releasing intrauterine devices, and copper intrauterine devices. Barrier methods must always be supplemented with the use of a spermicide. Note: Combined oral contraceptives are not recommended.\n\nExclusion Criteria:\n\n* Prior treatment with loncastuximab tesirine.\n* Prior treatment with mosunetuzumab or other CD20-directed bispecific antibodies.\n* Prior allogeneic stem cell transplantation.\n* Prior use of any monoclonal antibody, radioimmunoconjugate or ADC within 2 weeks prior to Day 1 of protocol therapy.\n* Treatment with any chemotherapeutic agent, or treatment with any other anti-cancer agent (investigational or otherwise) within 2 weeks or 5 half-lives of the drug, whichever is shorter, prior to Day 1 of protocol therapy.\n* Treatment with radiotherapy within 2 weeks prior to Day 1 of protocol therapy.\n\n  * If patients have received radiotherapy within 4 weeks prior to prior to Day 1 of protocol therapy, patients must have at least one measurable lesion outside of the radiation field. Patients who have only one measurable lesion that was previously irradiated but subsequently progressed are eligible.\n* Autologous stem cell transplantation (SCT) within 30 days prior to prior to Day 1 of protocol therapy.\n* Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days prior to Day 1 of protocol therapy.\n* Live vaccine within 30 days prior to Day 1 of protocol therapy.\n* Concomitant investigational therapy.\n* Treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents(e.g., immune checkpoint inhibitor therapies). Note: For certain prior treatments, such as CAR-T cell therapies, patients with prior immune-related Grade \\>= 3 adverse events (e.g., CRS) may be allowed after discussion with and approval by the Study PI.\n* Systemic steroid therapy or any other form of immunosuppressive therapy for lymphoma symptom control must be tapered down to =\\\u003C 20 mg\u002Fday prednisone or equivalent. Exceptions are:\n\n  * Inhaled or topical steroids\n  * Use of mineralocorticoids for management of orthostatic hypotension\n  * Use of physiologic doses of corticosteroids for management of adrenal insufficiency\n* Known hypersensitivity to biopharmaceutical produced in chinese hamster ovary (CHO) cells or history of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents.\n* Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath).\n* History of solid organ transplantation.\n* History of progressive multifocal leukoencephalopathy (PML).\n* Known or suspected history of hemophagocytic lymphohistiocytosis (HLH).\n* Clinically significant uncontrolled illness.\n* Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment.\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 ribonucleic acid (RNA). Testing to be done only in patients suspected of having infections or exposures.\n* Known active human immunodeficiency virus (HIV) infection. Subjects who have an undetectable or unquantifiable HIV viral load with CD4 \\> 200 and are on HAART medication are allowed. Testing to be done only in patients suspected of having infections or exposures.\n* Known or suspected chronic active Epstein-Barr virus (EBV) infection.\n* Known active central nervous system (CNS) involvement by lymphoma, including leptomeningeal involvement.\n* History of erythrema multiforme, Grade \\>= 3 rash, or blistering following prior treatment with immunomodulatory derivatives.\n* Symptomatic cardiac disease (including symptomatic ventricular dysfunction, symptomatic coronary artery disease, and symptomatic arrhythmias), cerebrovascular event\u002Fstroke or myocardial infarction within the past 6 months.\n* Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis.\n* Active autoimmune disease requiring treatment.\n* History of autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.\n\n  * Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.\n  * Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.\n  * Patients with a history of disease-related immune thrombocytopenic purpura, autoimmune hemolytic anemia, or other stable autoimmune diseases may be eligible.\n* Recent major surgery (within 4 weeks) prior to start of protocol therapy, other than for diagnosis.\n* History of another primary malignancy that has not been in remission for at least 2 years, with the following exceptions:\n\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) without evidence of disease\n  * Asymptomatic prostate cancer managed with a watch-and-wait strategy\n  * If the malignancy is expected to not require any treatment for at least 2 years (this exception should be discussed with the study PI).\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":92,"type":20},36,[94],"PHASE2","This phase II trial studies the safety and how well of loncastuximab tesirine when given together with mosunetuzumab works in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Loncastuximab tesirine is a monoclonal antibody, loncastuximab, linked to a toxic agent called tesirine. Loncastuximab attaches to anti-CD19 cancer cells in a targeted way and delivers tesirine to kill them. Mosunetuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving loncastuximab tesirine with mosunetuzumab may help treat patients with relapsed or refractory diffuse large B-cell lymphoma.",[97,98,63,99,29,100,101,102,69,103,33,104],"Recurrent Diffuse Large B-Cell Lymphoma","Recurrent Grade 3b Follicular Lymphoma","Recurrent Primary Mediastinal (Thymic) Large B-Cell Lymphoma","Recurrent Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma","Refractory Diffuse Large B-Cell Lymphoma","Refractory Grade 3b Follicular Lymphoma","Refractory Primary Mediastinal (Thymic) Large B-Cell Lymphoma","Refractory Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma","2026-05-07",{"date":107,"type":38},"2026-05-11",{"date":109,"type":38},"2024-01-02",{"date":111,"type":20},"2027-03-23",{"name":113,"class":45},"City of Hope Medical Center",{"id":115,"slug":116,"hasResults":11,"nctId":117,"briefTitle":118,"officialTitle":119,"acronym":4,"eligibilityCriteria":120,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":121,"targetDuration":4,"studyType":21,"phases":123,"briefSummary":124,"conditions":125,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":131,"lastUpdatePostDateStruct":132,"startDateStruct":134,"completionDateStruct":136,"leadSponsor":138,"locationsCount":46},"100605738","phase-1-anti-cd192022-chimeric-antigen-receptor-t-cells-tricar192022-t-cells-for-the-treatment-of-relapsed-or-refractory-non-hodgkin-lymphoma-acute-lymphoblastic-leukemia-and-chronic-lymphocytic-leukemia-100605738","NCT07166419","Anti-CD19\u002F20\u002F22 Chimeric Antigen Receptor T Cells (TriCAR19.20.22 T Cells) for the Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma, Acute Lymphoblastic Leukemia, and Chronic Lymphocytic Leukemia","Phase I Clinical Trial of Caring Cross Anti-CD19\u002F20\u002F22 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Lymphoid Malignancies (Non-Hodgkin Lymphoma, Acute Lymphoblastic Leukemia, Chronic Lymphocytic Leukemia) (C3PO)","Inclusion Criteria:\n\n* COHORT A: Subjects must have relapsed or refractory non-Hodgkin lymphoma with lesions ≤ 5 cm, indolent lymphomas, or chronic lymphocytic leukemia without Richter's transformation\n* COHORT B: Subjects with lymphoid blast crisis from chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia with Richter's transformation, non-Hodgkin lymphoma with lesions \\> 5 cm and\u002For lymphoblastic lymphoma, or non-Hodgkin lymphoma with circulating lymphoma cells\n* Subjects must have been treated with at least two lines of therapy; subjects with prior commercial or investigational CAR T therapy targeting CD19, and\u002For CD20, and\u002For CD22 are permitted. Disease must have either progressed after the last regimen or presented failure to achieve complete remission with the last regimen\n* Note: Cohort assignment at discretion of principal investigator (PI) depending on patient disease\u002F history\n* Subjects with relapsed\u002Frefractory CLL after at least 2 prior lines of appropriate therapy and must have previously received an approved Bruton's tyrosine kinase (BTK) inhibitor and venetoclax\n* In subjects who had a prior autologous stem cell transplant for refractory high-grade B-cell lymphoma who relapse within 12 months of autologous stem cell transplant are eligible\n* Subjects with relapsed\u002Frefractory acute B-lymphoblastic leukemia who received at least 2 prior lines of appropriate therapy. Subjects are also eligible if they have failed or are ineligible for allogeneic stem cell transplant\n* Subjects with relapsed\u002Frefractory lymphoid blast crisis from prior chronic myeloid leukemia (CML) who received at least 2 prior lines of therapy (tyrosine kinase inhibitors, multiagent chemotherapy) or have failed or are ineligible for allogeneic stem cell transplant\n* The patient's lymphoid malignancy must be positive for CD19 and\u002For CD20 and\u002For CD22, either by immunohistochemistry or flow cytometry analysis on the last biopsy available or peripheral blood for circulating disease\n* Subjects with prior commercial or investigational CAR T therapy targeting CD19, and\u002For CD20, and\u002For CD22 are permitted if it has been at least 30 days since previous CAR T cell therapy and \\\u003C 5% of circulating levels of CD3+ cells express the prior CAR by flow cytometry\n* Subjects who received antibodies targeting CD19, or CD20, or CD22 are eligible\n* Age ≥ 18 years\n* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2\n* Total bilirubin ≤ 1.5 times the institutional upper limit of normal\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) ≥ 3 x institutional upper limit of normal\n* Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) ≤ 3 x institutional upper limit of normal\n* Creatinine clearance more than or equal to 50 ml\u002Fmin calculated by the Cockcroft-Gault formula\n* Subjects must have adequate pulmonary function as defined as pulse oximetry ≥ 92% on room air\n* Subjects must have adequate cardiac function as defined as left ventricular ejection fraction ≥ 40% in the most recent echocardiogram\n* Absolute lymphocyte count ≥ 100\u002FuL; if white blood cell (WBC) is low and differential is not performed, CD3 count (helper\u002Fsuppressor) should be ≥ 100\u002Ful\n* Subjects (or legal guardians) must have the ability to understand and the willingness to sign a written informed consent document\n* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of \\\u003C 1% per year during the treatment period and for at least 6 months after the TriCAR19.20.22 T cell infusion\n\n  * A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (\\\u003C 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and\u002For uterus)\n  * Examples of contraceptive methods with a failure rate of \\\u003C 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptive s that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. 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* For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:\n\n  * With female partners of childbearing potential, men 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 6 months after the TriCAR19.20.22 T cell infusion. Men must refrain from donating sperm during this same period\n  * With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 6 months after the TriCAR19.20.22 T cell infusion to avoid potential embryonal or fetal exposure. 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\nExclusion Criteria:\n\n* Autologous transplant within 6 weeks of planned CAR-T cell infusion\n* Allogeneic stem cell transplant or donor lymphocyte infusion within 2 months of planned CAR-T cell infusion and patients must be off immunosuppressive agents\n* Subjects with live vaccines given 28 days prior to lymphodepleting (LD) chemotherapy will be excluded\n* Active graft versus host disease\n* Active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast). Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial (e.g. low Gleason score prostate cancer)\n* A minimum of 28 days must have elapsed between prior treatment with investigational agent(s) and the day of lymphocyte collection\n* HIV-seropositive patients are allowable, however must be on effective anti-retroviral therapy with undetectable viral load within 6 months of enrollment to be eligible for this trial\n* Subjects 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\n* 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. Women of childbearing potential must have a negative serum pregnancy test. 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\n* Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy\n* Subjects with a positive hepatitis B core antibody or surface antigen are at high risk for hepatitis B virus (HBV) reaction and will require entecavir\u002Ftenofivir prophylaxis or serial hepatitis B (Hep) B polymerase chain reaction (PCR) monitoring at the direction of an infectious disease specialist. Duration of prophylaxis to correspond with detection of TriCAR19.20.22 T cells\u002Fviral vector copies in serum or continued evidence of B-cell aplasia such as reduced intravenous immunoglobulin (IVIG) levels. No antiviral prophylaxis is indicated with hepatitis C positivity with negative PCR\n* Subjects with history of clinically relevant CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease\n* History of autoimmune disease (i.e. rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months",{"count":122,"type":20},24,[23],"This phase I trial tests the safety, side effects and best dose of anti-CD19\u002F20\u002F22 chimeric antigen receptor (CAR) T cells (TriCAR19.20.22 T cells) and how well they work in treating patients with non-Hodgkin lymphoma, acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein, such as CD19, CD20 and CD22, on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Giving TriCAR19.20.22 T cells may be safe, tolerable, and\u002For effective in treating patients with relapsed or refractory non-Hodgkin lymphoma, ALL and CLL.",[126,60,27,127,64,128,65,29,66,31,129,70,130,71,33],"Blast Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive","Recurrent Chronic Myeloid Leukemia, BCR-ABL1 Positive","Recurrent Lymphoblastic Lymphoma","Refractory Chronic Myeloid Leukemia, BCR-ABL1 Positive","Refractory Lymphoblastic Lymphoma","2026-04-10",{"date":133,"type":38},"2026-04-15",{"date":135,"type":38},"2026-01-14",{"date":137,"type":20},"2026-12-31",{"name":139,"class":45},"Ohio State University Comprehensive Cancer Center",{"id":141,"slug":142,"hasResults":11,"nctId":143,"briefTitle":144,"officialTitle":145,"acronym":4,"eligibilityCriteria":146,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":147,"targetDuration":4,"studyType":21,"phases":148,"briefSummary":149,"conditions":150,"keywords":157,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":160,"lastUpdatePostDateStruct":161,"startDateStruct":163,"completionDateStruct":165,"leadSponsor":166,"locationsCount":168},"100506386","phase-2-zanubrutinib-and-lisocabtagene-maraleucel-for-the-treatment-of-richters-syndrome-100506386","NCT05873712","Zanubrutinib and Lisocabtagene Maraleucel for the Treatment of Richter's Syndrome","A Phase II Study Evaluating the Safety and Efficacy of the Combination of Zanubrutinib Plus Lisocabtagene Maraleucel for Richter's Syndrome","Inclusion Criteria:\n\n* Diagnosis of RS - occurrence of diffuse large B-cell lymphoma (DLBCL) in patients with antecedent or concurrent CLL\u002FSLL (CLL\u002FSLL diagnosis per IWCLL 2018 criteria).\n* Must have relapsed\u002Frefractory disease as defined by one of the following:\n\n  * Participants must have undergone \\>= 1 prior systemic therapeutic regimen administered for \\>= 1 cycle for either CLL or RS, and have had either documented disease progression to the most recent treatment regimen, or refractory disease. OR\n  * Developed RS while receiving treatment for CLL\n* Age \\>= 18 years\n* Eastern Cooperative Oncology Group (ECOG) performance status =\\\u003C 2\n* Total bilirubin =\\\u003C 2.0 times the institutional upper limit of normal (unless documented Gilbert's syndrome)\n* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \\[SGOT\\]) =\\\u003C 2.5 x institutional upper limit of normal\n* Alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase \\[SGPT\\]) =\\\u003C 2.5 x institutional upper limit of normal\n* Creatinine clearance \\>= 30 mL\u002Fmin\n\n  * Using 24-hour creatinine clearance or standard Cockcroft-Gault equation\n* Absolute lymphocyte count \\> 100\u002FuL at screening\n* Left ventricular ejection fraction \\>= 40% by multigated acquisition (MUGA) or echocardiogram (ECHO)\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\u002Fsmall lymphocytic lymphoma (SLL). If cytopenias are due to disease in the bone marrow any degree of anemia or thrombocytopenia are allowed, absolute neutrophil count (ANC) must be \\>= 500\n* Absolute neutrophil count (ANC) \\>= 1000\u002Fmm\\^3 (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). If cytopenias are due to disease in the bone marrow any degree of anemia or thrombocytopenia are allowed, ANC must be \\>= 500\n* Platelets \\>= 30,000\u002Fmm\\^3 (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). If cytopenias are due to disease in the bone marrow any degree of anemia or thrombocytopenia are allowed\n* Hemoglobin \\>= 7 g\u002FdL (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). If cytopenias are due to disease in the bone marrow any degree of anemia or thrombocytopenia are allowed\n* Radiographically measurable lymphadenopathy (or measurable extra-nodal disease) per Lugano criteria\n* Must meet all institutional standards for receiving CAR T-cell therapy\n* Subjects (or legal guardians) must have the ability to understand and the willingness to sign a written informed consent document\n* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of \\\u003C 1% per year, initiated prior to first dose of study drug, during the treatment period and for at least 1 year after the CAR-T cell infusion or 1 month after last dose of zanubrutinib, whichever is longer.\n\n  * A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (\\\u003C 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and\u002For uterus). 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* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:\n\n  * With female partners of childbearing potential, men 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 1 year after the anti-CD19 CAR-T cell infusion or 1 month after last dose of zanubrutinib, whichever is longer. Men should avoid fathering a child and refrain from donating sperm during this same period.\n  * With pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 1 year after the human anti- CD19 CAR-T cell infusion or 1 month post last dose of zanubrutinib, whichever is longer, to avoid potential embryonal or fetal exposure. 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\nExclusion Criteria:\n\n* A history of treatment including any of the following: prior CD19 directed therapy, treatment with alemtuzumab within 6 months before enrollment, prior allogeneic hematopoietic stem cell transplant (SCT) or donor lymphocyte infusion (DLI) within 2 months prior to enrollment\n* Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD), or requiring immunosuppressive drugs for treatment of GVHD, or have taken calcineurin inhibitors within 4 weeks prior to consent\n* Inadequate recovery from adverse events related to prior therapy to grade =\\\u003C 1 (excluding grade 2 alopecia, neuropathy, and hypertension)\n* Is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication\n* Active bleeding or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease)\n* Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP)\n* Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening\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\u002Fflutter can enroll on study\n* Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists\n* Prothrombin time (PT)\u002Finternational normalized ratio (INR) or activated partial thromboplastin time (PTT) (in the absence of lupus anticoagulant) \\> 2 x upper limit normal (ULN)\n* Treatment with a moderate or strong CYP3A inhibitor or inducer within 7 days prior to first dose of zanubrutinib\n* Patients may not have an active intercurrent disease or concurrent malignancy that is expected to limit survival to \\\u003C 5 years\n* Human immunodeficiency virus (HIV) seropositivity at screening\n* Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, unstable angina pectoris, pulmonary abnormalities or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements\n* 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. Women of childbearing potential must have a negative serum pregnancy test. 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\n* Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy\n* Serologic status reflecting active hepatitis B or C infection at screening. Patients 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) at screening. PCR positive patients will be excluded\n* History of autoimmune disease (i.e. rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months\n* Chronic use of corticosteroids \\>= 20mg prednisone equivalent PO daily\n* Live vaccines given in 28 days prior to lymphodepleting chemotherapy",{"count":122,"type":20},[94],"This phase II trial tests how well zanubrutinib and lisocabtagene maraleucel (liso-cel) work together in treating patients with Richter's syndrome that has come back (recurrent) or does not respond to treatment (refractory). Richter's syndrome occurs when chronic lymphocytic leukemia and\u002For small lymphocytic leukemia transforms into an aggressive lymphoma, which is a cancer of the lymph nodes. Zanubrutinib is a class of medication called a kinase inhibitor. These drugs work by preventing the action of abnormal proteins that tell cancer cells to multiply, which helps stop the spread of cancer. Liso-cel is a type of treatment known as chimeric antigen receptor (CAR) T cell therapy. CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Giving zanubrutinib and liso-cell together may kill more cancer cells in patients with recurrent or refractory Richter's syndrome.",[29,33,151,152,153,154,155,156],"Transformed Chronic Lymphocytic Leukemia to Diffuse Large B-Cell Lymphoma","Recurrent Transformed B-Cell Non-Hodgkin Lymphoma","Recurrent Transformed Non-Hodgkin Lymphoma","Refractory Transformed Non-Hodgkin Lymphoma","Refractory Transformed B-cell Non-Hodgkin Lymphoma","Refractory Transformed",[158,159],"Richter's Transformation","Richter's Syndrome","2026-02-27",{"date":162,"type":38},"2026-03-03",{"date":164,"type":38},"2023-07-28",{"date":137,"type":20},{"name":167,"class":45},"Aseel Alsouqi",3,{"id":170,"slug":171,"hasResults":11,"nctId":172,"briefTitle":173,"officialTitle":174,"acronym":4,"eligibilityCriteria":175,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":176,"targetDuration":4,"studyType":21,"phases":178,"briefSummary":179,"conditions":180,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":188,"lastUpdatePostDateStruct":189,"startDateStruct":191,"completionDateStruct":193,"leadSponsor":195,"locationsCount":46},"100530830","phase-1-b-cell-activating-factor-receptor-baffr-based-chimeric-antigen-receptor-t-cells-with-fludarabine-and-cyclophosphamide-lymphodepletion-for-the-treatment-of-relapsed-or-refractory-b-cell-hematologic-malignancies-100530830","NCT06191887","B-Cell Activating Factor Receptor (BAFFR)-Based Chimeric Antigen Receptor T-Cells With Fludarabine and Cyclophosphamide Lymphodepletion for the Treatment of Relapsed or Refractory B-cell Hematologic Malignancies","Phase 1a\u002F1b Dose Escalation and Cohort Expansion Study of the Safety and Efficacy of B-Cell Activating Factor Receptor (BAFFR)-Based Chimeric Antigen Receptor T-Cells (MC10029) in Subjects With Relapsed or Refractory BAFFR-Expressing B-Cell Hematologic Malignancies","Inclusion Criteria:\n\n* PRE-REGISTRATION: Age ≥ 18 years\n* PRE-REGISTRATION: Confirmed diagnosis of 1 of the following relapsed or refractory B-cell hematologic malignancies: chronic lymphocytic leukemia\u002Fsmall lymphocytic lymphoma (CLL\u002FSLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), or large B cell lymphoma (LBCL) including Richter's transformation from CLL\u002FSLL\n\n  * For CD19+ B cell malignancies; relapsed or refractory disease is defined by one of the following histopathology:\n\n    * Biopsy proven SLL or flow cytometry proven CLL; relapsed or refractory disease is defined as:\n    * Demonstration of progressive or stable disease by positron emission tomography\u002Fcomputed tomography (PET\u002FCT) or computed tomography (CT) criteria according to the international workshop on chronic lymphocytic leukemia (iwCLL) 2018 criteria\n    * Biopsy proven B-cell non-Hodgkin lymphoma (NHL) of any histopathology (including Richter Transformation of CLL); relapsed or refractory disease is defined as:\n    * Demonstration of progressive or stable disease by PET\u002FCT or CT criteria as the best response to the most recent chemotherapy regimen according to the revised Lugano Response Criteria for Malignant Lymphoma\n* PRE-REGISTRATION: Disease Specific prior lines of therapies below:\n\n  * For CLL\u002FSLL, patients must have received ≥ two prior lines of therapy, and\u002For ≥ 6 months of second line prior BTK inhibition (e.g. ibrutinib or other such as acalabrutinib or zanubrutinib) and must have failed to respond to venetoclax or be intolerant. Exception: Patients in stable disease (SD) or partial response (PR) with a known ibrutinib resistance mutation (BTK or phospholipase Cγ2) may be included even if on ibrutinib therapy for less than 6 months\n\n    * These patients may or may not have received prior antibody directed against cluster of differentiation 20 (CD20).\n  * For Follicular Lymphoma, patients must have received ≥ two prior lines of therapy, including an antibody directed against CD20.\n\n    * NOTE: Prior cluster of differentiation 19 (CD19) directed chimeric antigen receptor T-cell therapy (CART) must have a 100-day washout period.\n  * For Mantle Cell Lymphoma, patients must have received ≥ two prior lines of therapy, including an antibody directed against CD20, and a BTK inhibitor.\n\n    * NOTE: Prior CD19 directed CART must have a 100-day washout period.\n  * For Marginal Zone Lymphoma, patients must have received ≥ two prior lines of therapy, including an antibody directed against CD20.\n\n    * NOTE: Prior CD19 directed CART must have a 100-day washout period.\n  * For Large B cell Lymphoma, patients must have received ≥ two prior lines of therapy, including an antibody directed against CD20. Prior exposure to CD19 directed CART will be allowed at the discretion of the Principal Investigator.\n\n    * NOTE: Prior failed CD19 directed CART must have a 100-day washout period\n  * For Richter's Transformation, patients must have received ≥two prior lines of therapy, including an antibody directed against CD20.\n  * 100-day washout period starts from the date of the last prior CAR-T infusion.\n* PRE-REGISTRATION: Measurable disease\n* REGISTRATION: Positive BAFFR test\n* REGISTRATION: Measurable disease\n* REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2\n* REGISTRATION: Hemoglobin ≥ 9.0 g\u002FdL (unless due to documented marrow involvement with disease) obtained ≤14 days prior to registration\n* REGISTRATION: Absolute neutrophil count (ANC) ≥ 1500\u002Fmm\\^3 (unless due to documented marrow involvement with disease) obtained ≤14 days prior to registration\n* REGISTRATION: Platelet count ≥100,000\u002Fmm\\^3 (unless due to documented marrow involvement with disease) obtained ≤ 14 days prior to registration\n* REGISTRATION: Total bilirubin ≤ 1.5 x upper limits of normal (ULN) (Subjects with Gilbert's Syndrome may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN) obtained ≤ 14 days prior to registration\n* REGISTRATION: Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement) obtained ≤ 14 days prior to registration\n* REGISTRATION: Prothrombin time (PT)\u002Finternational normalized ratio (INR) \u002Factivated partial thromboplastin time (aPTT) ≤ 1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy obtained ≤ 14 days prior to registration\n\n  * Patients on a stable, maintenance regimen of anticoagulant therapy for ≥ 30 days prior to registration may have PT\u002FINR measurements \\> 1.5 X ULN if, in the judgment of the investigator, the patient is suitable for the study\n* REGISTRATION: Calculated creatinine clearance ≥45 ml\u002Fmin using the Cockcroft-Gault formula obtained ≤ 14 days prior to registration\n* REGISTRATION: Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required\n* REGISTRATION: Provide written informed consent understand and comply with protocol-required study procedures\n* REGISTARTION: Patients must have an ejection fraction (EF) of ≥ 45%\n* REGISTRATION: Patients must have pulse ox measurements of \\> 92% on room air\n* REGISTRATION: Willingness to provide mandatory blood specimens for correlative research\n* REGISTRATION: Willing to return to enrolling institution for study follow-up\n\nExclusion Criteria:\n\n* PRE-REGISTRATION: Prior solid organ transplantation\n* PRE-REGISTRATION: Unstable angina, clinically significant arrhythmia, or myocardial infarction ≤ 6 months of prior to pre-registration, or grade 3 or higher pericardial effusion at the time of pre-registration\n* PRE-REGISTRATION: Prior anti-BAFF-R therapies\n* PRE-REGISTRATION: Known contraindication to lymphodepleting (LD) chemotherapy\n* PRE-REGISTRATION: Use of systemic antitumor therapy or investigational agent ≤ 14 days, prior to pre-registration\n* PRE-REGISTRATION: Receiving any other investigational agent which would be considered as a treatment for the BAFF-R\n* PRE-REGISTRATION: Autologous HCT ≤ 60 days prior to pre-registration\n* PRE-REGISTRATION: Uncontrolled intercurrent non-cardiac illness including, but not limited to:\n\n  * Previous or concurrent malignancy\n  * Ongoing or active infection\n  * Psychiatric illness\u002Fsocial situations\n  * Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy \\* Persons of childbearing potential who are pregnant or breastfeeding\n  * Life Expectancy of \\\u003C 6 weeks\n  * Persons requiring systemic corticosteroids (\\>10 mg prednisone or equivalent per day) and\u002For other immunosuppressive therapy. Patients are allowed to use topical corticosteroids\n  * Any other conditions that would limit compliance with study requirements\n* PRE-REGISTRATION: Detectable malignant cells from cerebrospinal fluid (CSF) or magnetic resonance imaging (MRI) indicating brain metastases during screening, or a history of central nervous system (CNS) involvement by malignancy (CSF or imaging) with still active disease. Note: Patients with a history of CNS involvement resolving after treatment and without active disease will be considered eligible if other inclusion criteria are met\n* PRE-REGISTRATION: History of a seizure disorder, major cerebrovascular ischemia\u002Fhemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement\n* PRE-REGISTRATION: Radiation therapy ≤ 14 days prior to pre-registration\n* PRE-REGISTRATION: Prior allogeneic hematopoietic stem cell transplant (HCT) in ≤ 6 months prior to pre-registration; patients with active graft versus host disease (GVHD) will not be eligible regardless of duration from prior allogeneic HCT\n* PRE-REGISTRATION: Human immunodeficiency virus (HIV) positive patients\n* PRE-REGISTRATION: Subjects with New York Health Association (NYHA) class III or greater heart failure\n* REGISTRATION: Eligible for auto-HCT based on investigator judgement\n* REGISTRATION: Presence of active bacterial, viral, or fungal infection that is uncontrolled, based on investigator judgment\n* REGISTRATION: Patients with active hepatitis B or hepatitis C infections are excluded from the study. Patients who are documented to be HIV positive or proven HIV infection from testing are ineligible for the study. Infectious disease testing (HIV-1, HIV-2, hepatitis C virus (HCV) antibody and polymerase chain reaction (PCR), hepatitis B virus (HBV) surface antigen, HBV surface antibody, HBV core antibody) performed ≤ 45 days prior to registration may be considered for subject eligibility\n* REGISTRATION: Previous or concurrent malignancy, except basal cell or squamous cell skin carcinoma, adequately resected and in situ carcinoma of cervix, or a previous malignancy that was completely resected and has been in remission for ≥ 5 years prior to registration\n* REGISTRATION: Persons of childbearing potential who are pregnant or breastfeeding\n* REGISTRATION: Life expectancy of \\\u003C 6 weeks",{"count":177,"type":20},27,[23],"This phase I trial tests safety, side effects and best dose of B-cell activating factor receptor (BAFFR)-based chimeric antigen receptor T-cells, with fludarabine and cyclophosphamide lymphodepletion, for the treatment of patients with B-cell hematologic malignancies that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). BAFFR-based chimeric antigen receptor T-cells is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Giving chemotherapy, such as fludarabine and cyclophosphamide, helps ill cancer cells in the body and helps prepare the body to receive the BAFFR based chimeric antigen receptor T-cells. Giving BAFFR based chimeric antigen receptor T-cells with fludarabine and cyclophosphamide for lymphodepletion may work better for the treatment of patients with relapsed or refractory B-cell hematologic malignancies.",[181,27,97,182,183,184,28,29,31,101,185,186,187,32,33],"B-Cell Non-Hodgkin Lymphoma","Recurrent Follicular Lymphoma","Recurrent Mantle Cell Lymphoma","Recurrent Marginal Zone Lymphoma","Refractory Follicular Lymphoma","Refractory Mantle Cell Lymphoma","Refractory Marginal Zone Lymphoma","2026-02-11",{"date":190,"type":38},"2026-02-13",{"date":192,"type":38},"2024-03-18",{"date":194,"type":20},"2040-12-31",{"name":44,"class":45},{"id":197,"slug":198,"hasResults":11,"nctId":199,"briefTitle":200,"officialTitle":201,"acronym":4,"eligibilityCriteria":202,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":203,"targetDuration":4,"studyType":21,"phases":205,"briefSummary":206,"conditions":207,"keywords":4,"overallStatus":34,"whyStopped":4,"lastUpdateSubmitDate":209,"lastUpdatePostDateStruct":210,"startDateStruct":212,"completionDateStruct":214,"leadSponsor":216,"locationsCount":46},"100572622","phase-1-zanubrutinib-in-combination-with-odronextamab-for-the-treatment-of-patients-with-richters-transformation-100572622","NCT06735664","Zanubrutinib in Combination With Odronextamab for the Treatment of Patients With Richter's Transformation","A Phase I Study of Covalent BTK Inhibitor Zanubrutinib in Combination With a CD3-CD20 Bispecific Antibody Odronextamab in Patients With Richter's Transformation","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* Age: ≥ 18 years\n* Eastern Cooperative Oncology Group (ECOG) ≤ 2\n* Histologically confirmed diagnosis of Richter transformation (RT; transformed CLL). Only patients who have diffuse large B-cell lymphoma histology in transformation are eligible (for example, patients with transformation into Hodgkin lymphoma subtype are not eligible)\n* Evidence of CD20 positivity at screening (by immunohistochemistry \\[IHC\\] or flow cytometry)\n* Treatment naïve or relapsed\u002F refractory disease. Patients with either previously untreated RT and previously treated RT are eligible, regardless of whether or not they had received CLL-directed therapy\n* Radiographically measurable lymphadenopathy (≥ 1.5 cm) or splenomegaly, or bone marrow involvement by diffuse large B cell lymphoma (DLBCL)\u002FRT\n* Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy\n* Without bone marrow involvement: Absolute neutrophil count (ANC) ≥ 1,000\u002Fmm\\^3\n\n  * NOTE: A participant may not have received granulocyte colony stimulating factor (G-CSF) within 3 days of first dose of the assigned study treatment in order to meet this eligibility requirement\n* With bone marrow involvement: ANC ≥ 500\u002Fmm\\^3\n\n  * NOTE: A participant may not have received granulocyte colony stimulating factor (G-CSF) within 3 days of first dose of the assigned study treatment in order to meet this eligibility requirement\n* Without bone marrow involvement: Platelets ≥ 50,000\u002Fmm\\^3\n\n  * NOTE: A participant may not have received platelet transfusion within 7 days of first dose of the assigned study treatment in order to meet this eligibility requirements\n* With bone marrow involvement: Platelets ≥ 25,000\u002Fmm\\^3\n\n  * NOTE: A participant may not have received platelet transfusion within 7 days of first dose of the assigned study treatment in order to meet this eligibility requirements\n* With bone marrow involvement: Hemoglobin (Hgb) ≥ 7 g\u002FdL\n* Total bilirubin ≤ 2 x upper limit of normal (ULN) or ≤ 3 x ULN for Gilbert's disease or compensated hemolysis directly attributable to CLL\n* Aspartate aminotransferase (AST) ≤ 3 x ULN\n* Alanine aminotransferase (ALT) ≤ 3 x ULN\n* Alkaline phosphatase (ALP) ≤ 2.5 x ULN or ≤ 5 x ULN if attributed to lymphoma involvement of the liver\n* Serum creatinine ≤ 1.5 x ULN OR creatinine clearance of ≥ 50 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\n* 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\n* If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants\n* Left ventricular ejection fraction (LVEF) ≥ 45%\n\n  * Note: To be performed within 28 days prior to day 1 of protocol therapy\n* Seronegative for hepatitis C virus (HCV), hepatitis B virus (HBV) (surface antigen negative) and no history of HIV OR\n\n  * If seropositive for HBV or HCV, nucleic acid quantitation must be performed. Viral load must be undetectable\n  * HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* Women of childbearing potential (WOCBP): Negative serum pregnancy test\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 through at least 6 months after the last dose of study therapy. Sperm donation is prohibited during the study and for 6 months after the last dose of the assigned study treatment. Highly effective contraceptive measures include:\n\n  * Stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated ≥ 2 menstrual cycles prior to screening\n  * Intrauterine device (IUD); intrauterine hormone-releasing system (IUS)\n  * Bilateral tubal ligation\u002Focclusion\n  * Vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the study patient and that the partner has obtained medical assessment of surgical success for the procedure)\n  * Sexual abstinence, only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drugs\n  * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \\> 1 year (women only)\n  * A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) 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 FSH measurement is insufficient to determine the occurrence of a postmenopausal state. The above definitions are according to the clinical trial facilitation group guidance. Pregnancy testing and contraception are not required\n\nExclusion Criteria:\n\n* Allogeneic bone marrow or organ transplant within 6 months or evidence of active graft versus host diseae (GVHD)\n* Prior CD20-targeted bispecific antibody therapy\n* Chronic systemic corticosteroid use \\> 10 mg\u002Fday of prednisone or equivalent within 72 hours (h) of start of study treatment. Patients who received corticosteroid treatment with ≤ 10 mg\u002Fday of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to day 1 of cycle 1. Patients may have received a brief (≤ 10 days) course of systemic steroids (≤ 80 mg prednisone equivalent per day) up to 24 hours prior to initiation of study therapy for control of lymphoma-related symptoms\n* Therapeutic anticancer antibodies within 2 weeks prior to day 1 of protocol therapy\n* Radio- or toxin-immunoconjugates within 10 weeks prior to day 1 of protocol therapy\n* Live vaccine within 28 days prior to day 1 of protocol therapy\n* Any investigational therapy within 28 days or 5 half-lives of the drug, whichever is shorter, prior to the start of study treatment\n* Standard radiotherapy within 14 days of first administration of study treatment\n* Prior organ transplantation\n* Chemotherapy, within 2 weeks prior to day 1 of protocol therapy; targeted therapy within 6 half-lives or two weeks, whichever is shorter\n* Requires treatment with a strong CYP3A4 inducers\u002F inhibitor while on protocol therapy\n* Uncontrolled immune hemolysis or thrombocytopenia\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drug\n* Known hypersensitivity to both allopurinol and rasburicase\n* Unstable cardiac disease as defined by one of the following:\n\n  * Cardiac events such as myocardial infarction (MI) within the past 6 months\n  * NYHA (New York Heart Association) heart failure class III-IV\n  * Uncontrolled atrial fibrillation or hypertension\n* Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before the start of study treatment\n* Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months)\n* Active uncontrolled cardiac arrythmia\n* History or concurrent condition of interstitial lung disease and\u002For severely impaired lung function\n* Evidence of central nervous system (CNS) involvement within 6 months prior to initiation of study therapy\n* Major surgery (under general anesthesia) within 30 days prior to day 1 of protocol therapy\n* Clinically significant uncontrolled illness\n* Evidence of any active infection (bacterial, viral, fungal, mycobacterial, parasitic or other) at study enrollment or within 2 weeks of study enrollment, if requiring ongoing treatment and\u002For has the potential to cause disseminated disease or severe infection upon immunosuppression. There should be evidence that the infection has cleared or is well controlled by start of study therapy\n* Active COVID-19 infection\n* Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)\n\n  * NOTE: Participants with HIV who have controlled infection (undetectable viral load and CD4 count above 350 cells\u002FuL either spontaneously or on a stable antiviral regimen) are permitted\n  * NOTE: Participants who are hepatitis B surface antigen positive or who are hepatitis B core antibody positive should undergo evaluation by a specialist and be considered to have controlled infection (serum hepatitis B virus deoxyribonucleic acid \\[DNA\\] polymerase chain reaction \\[PCR\\] that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) before they are permitted onto study\n  * NOTE: Participants who are HCV antibody positive who have controlled infection (undetectable HCV ribonucleic acid \\[RNA\\] by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted\n* Cytomegalovirus (CMV) infection as noted by detectable levels on peripheral blood polymerase chain reaction (PCR) assay. Patients who show detectable levels of CMV at screening will need to be treated with appropriate antiviral therapy and demonstrate at least 2 undetectable levels of CMV by PCR assay (at least 7 days apart) before being re-considered for eligibility\n* Other active malignancy. Patients with a prior (in the past 5 years) or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. History of the following is allowed:\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* Females only: Pregnant or breastfeeding\n* Inability to swallow and retain oral medication\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":204,"type":20},23,[23],"This phase I trial tests the safety and side effects of zanubrutinib in combination with odronextamab and how well it works in treating patients with Richter's transformation. Zanubrutinib, a tyrosine kinase inhibitor, blocks a protein called Bruton tyrosine kinase (BTK), which may help keep cancer cells from growing. Odronextamab is a bispecific monoclonal antibody that can bind to two different antigens at the same time. Odronextamab binds to CD20 found on B-cells (a type of white blood cell) and on many B-cell cancers and to CD3 on T-cells (also a type of white blood cell) and may interfere with the ability of cancer cells to grow and spread. Giving zanubrutinib in combination with odronextamab may be safe, tolerable and\u002For effective in treating patients with Richter's transformation.",[29,33,208,151],"Richter Syndrome","2025-09-14",{"date":211,"type":38},"2025-09-16",{"date":213,"type":38},"2025-08-14",{"date":215,"type":20},"2027-12-13",{"name":113,"class":45}]