[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"small-lymphocytic-leukemia-sll\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:small-lymphocytic-leukemia-sll":27},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,46],{"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":28,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":34,"lastUpdatePostDateStruct":35,"startDateStruct":38,"completionDateStruct":40,"leadSponsor":42,"locationsCount":45},"100349029","phase-2-study-of-zanubrutinib-obinutuzumab-and-venetoclax-in-patients-with-chronic-lymphocytic-leukemia-cll-or-small-lymphocytic-leukemia-sll-100349029",false,"NCT03824483","Study of Zanubrutinib, Obinutuzumab, and Venetoclax in Patients With Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL)","Phase 2 Study of Zanubrutinib, Obinutuzumab, and Venetoclax in Previously Untreated Patients With Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) and Mantle Cell Lymphoma (MCL)","Inclusion Criteria:\n\n\\- Signed, informed consent\n\n* Ability and willingness to comply with the requirements of the study protocol\n* Age ≥18 years\n* Diagnosis of the following histories according to the WHO criteria\n\n  1. CLL or SLL\n  2. MCL\n* For patients with SLL, peripheral blood flow cytometry must be positive with CLL-like cells accounting for at least 1% of circulating WBC.\n* No prior systemic therapy for disease under study except:\n\n  1. prior local radiation for symptomatic disease is permitted\n  2. Short course systemic corticosteroids is permissible for disease control, improvement of performance status or non-cancer indication (must be ≤ 14 days and \\\u003C 100 mg\u002Fday prednisone or ≤ 20 mg\u002Fday dexamethasone). Steroids must be discontinued prior to study treatment. Inhaled steroids for asthma, topical steroids, and replacement\u002FStress corticosteroids are permitted. Low-dose steroids for ITP are also permitted up to the equivalent prednisone 20mg\u002Fdaily at time of eligibility review.\n* ECOG performance status of 0 to 2\n* Adequate hematologic parameters unless due to disease under study:\n\n  1. Absolute neutrophil count (ANC) ≥1.0 x 109\u002FL unless neutropenia is clearly due to disease under study (per investigator discretion)\n  2. Platelet count ≥ 75,000\u002Fmm3 - OR - Platelet count ≥ 20,000\u002Fmm3 if thrombocytopenia is clearly due to disease under study (per investigator discretion)\n  3. Hemoglobin ≥9.0 g\u002FdL unless anemia is clearly due to marrow involvement due to disease under study (per investigator discretion)\n* Adequate renal and hepatic function, per laboratory reference range at Screening as follows:\n\n  a. AST\u002FSGOT, ALT\u002FSGPT ≤2.0 x ULN b. Total bilirubin ≤ 2.0 x ULN unless:\n\n  i. Considered secondary to Gilbert\"s syndrome, in which case ≤3 x ULN ii. Considered due to disease under study (Per PI or Co-PI discretion)\n\n  c. Creatinine clearance of eGFR\\>30 mL\u002Fmin according to the Cockcroft-Gault Equation\n* For females of childbearing potential, a negative serum pregnancy test within 7 days of study treatment\n* For female patients of childbearing potential, agreement 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) or remain abstinent (refrain from heterosexual intercourse) during the treatment period and to continue its use for 90 days after the last dose of zanubrutinib AND 30 days after the last dose of venetoclax AND for 18 months after the last dose of obinutuzumab (whichever date is later)\n\nA woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (\\>\u002F= 12 continuous months of amenorrhea with no identified cause other than menopause), and it not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and\u002For uterus) or another cause as determined by the investigator (e.g., Mullerian agenesis). The definition of childbearing potential may be adapted for alignment with local guidelines or regulations.\n\nExamples of contraceptive methods with a failure rate of \\\u003C1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. Hormonal contraceptive methods must be supplemented by a barrier method.\n\n1. 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\n   * For men with a female partner of childbearing potential or a pregnant female partnet: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom during the treatment period and to continue its use for 90 days after the last dose of zanubrutinib AND, 30 days after the last dose of venetoclax AND for 18 months after the last dose of obinutuzumab (whichever date is later)\n\n   The reliability of sexual abstinence should be evaluated in relation 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 - Willingness to not donate or bank sperm or oocytes during the entire study treatment period and after treatment discontinuation for 90 days after the last dose of zanubrutinib AND 30 days after the last dose of venetoclax AND for 18 months after the last dose of obinutuzumab (whichever date is later)\n\n   Additional Eligibility Criteria for CLL Cohort:\n\n   1\\. Diagnosis of untreated CLL or SLL according to WHO criteria 2. For patients with SLL, peripheral blood flow cytometry must be positive with CLL-like cells accounting for at least 1% of circulating WBC 3. No prior systemic therapy for CLL: prior single site of local radiation for symptomatic disease is permitted 4. Subject requires treatment according to IWCLL guidelines (See Appendix A)\n\n   Additional Eligibility Criteria for TP53 Mutant MCL cohorts:\n\n   1\\. Diagnosis of untreated stage II-IV mantle cell lymphoma\n\na. Prior radiotherapy for localized disease is permitted 2. Presence of TP53 mutation irrespective of variant allele frequency (TP53 cohort)\n\nOR\n\nPresence of p53 overexpression by immunohistochemistry defined as strong nuclear staining of \\>30% positive nuclei.\n\nAdditional Eligibility Criteria for Transplant Ineligible MCL cohort:\n\n1. Diagnosis of untreated stage II-IV mantle cell lymphoma\n\n   1. Prior radiotherapy for localized disease is permitted\n2. Patients must meet one of the following criteria (a or b):\n\n   a. Age ≥65 years If age \\\u003C65 years of age, then patients must be ineligible for HDT\u002FASCT on the basis of comorbidity or organ dysfunction.\n\n   Specifically, patients must meet at least one of the following criteria below:\n\n   i.. Comorbid disease, such as CAD, CHF, pulmonary dysfunction, liver or kidney dysfunction, precluding high dose therapy secondary to expected increased morbidity and mortality. ii. ECOG 2 iii. Ejection fraction ≥35% and \\\u003C45% iv. Impaired pulmonary function test with DLCO \\\u003C50% expected v. Medical conditions which in the opinion of the treating physician in consultation with the study PI or Co-PI and DMT preclude HDT\u002FASCT.\n\n   Exclusion Criteria:\n\n   Other malignancies:\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\n   * Other diagnosis of active cancer\n\n   Co-morbidities:\n\n   \\- Any uncontrolled illness that in the opinion of the investigator would preclude administration of study therapy (e.g. significant active infections, hypertension, angina, arrhythmias, pulmonary disease, or autoimmune dysfunction)\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 4 weeks prior to Cycle 1, Day 1\n   * Known bleeding diathesis\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\n\n     1. Patients with a history of HIV infection that is well controlled on antiretroviral therapy are eligible if all of the following criteria are met: (1) undetectable HIV viral load by standard clinical assay AND (2) CD4+ T cell count of ≥ 200 cells\u002Fmicroliter\n\n   NOTE: Many HIV regimens are excluded based on drug interactions, and concomitant antiretroviral therapy need to cleared by the clinical pharmacist and approved by the site PI)\n   * Active hepatitis B (chronic or acute) or hepatitis C infection a. 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\n     b. 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   * Inability to swallow a large number of tablets\n\n   Concomitant medications and drug interactions:\n\n   \\- Administration within 7 days prior to the first dose of study drug or concurrent therapy with strong inhibitors or inducers of CYP3A, CYP2C8, CYP2C9 and CYP2C19. The same applied for moderate inhibitors or inducers of CY\\_3A\n   * Live-virus vaccines given within 28 days prior to the initiation of study treatment\n   * Immunotherapy\n   * Hormone therapy (other than contraceptives, hormone replacement therapy, or megestrol acetate)\n   * Any therapies intended for the treatment of lymphoma\u002Fleukemia whether FDA approved or experimental (outside of this study)\n   * Radiation therapy intended to treat MCL or CLL\u002FSLL\n   * Warfarin or warfarin derivatives\n   * Consumption of one or more of the following within 3 days prior to the first dose of study drug:\n\n   Grapefruit or grapefruit products Seville oranges, including marmalade containing Seville oranges Star Fruit (carambola)\n\n   Prior therapy:\n   * Prior anti-CD20 monoclonal antibody therapy for non-malignant indication\n   * Obinutuzumab is contraindicated in patients with a known hypersensitivity (IgE-mediated) reaction to obinutuzumab or to any of its excipients\n   * Prior systemic therapy for CLL; prior single site of local radiation for symptomatic disease is permitted\n\n   Other:\n   * Females who are currently pregnant or breastfeeding\n   * Participation in a separate investigational therapeutic study unless authorized by the investigator","ALL","18 Years",{"count":19,"type":20},230,"ESTIMATED","INTERVENTIONAL",[23],"PHASE2","The purpose of this study is to determine the rate of minimum residual disease (MRD) negative response (i.e. the rate of no evidence of disease) of the study drugs, zanubrutinib, obinutuzumab, and venetoclax, given in combination as a treatment for CLL and\u002For SLL.",[26,27],"Chronic Lymphocytic Leukemia (CLL)","Small Lymphocytic Leukemia (SLL)",[29,30,31,32],"Zanubrutinib","Obinutuzumab","Venetoclax","18-427","RECRUITING","2026-05-06",{"date":36,"type":37},"2026-05-07","ACTUAL",{"date":39,"type":37},"2019-02-22",{"date":41,"type":20},"2027-02",{"name":43,"class":44},"Memorial Sloan Kettering Cancer Center","OTHER",8,{"id":47,"slug":48,"hasResults":11,"nctId":49,"briefTitle":50,"officialTitle":50,"acronym":4,"eligibilityCriteria":51,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":52,"targetDuration":4,"studyType":21,"phases":54,"briefSummary":55,"conditions":56,"keywords":4,"overallStatus":33,"whyStopped":4,"lastUpdateSubmitDate":58,"lastUpdatePostDateStruct":59,"startDateStruct":61,"completionDateStruct":63,"leadSponsor":65,"locationsCount":67},"100590453","phase-2-phase-ii-study-of-combined-pirtobrutinib-venetoclax-and-obinutuzumab-pvo-time-limited-treatment-for-patients-with-recurrent-chronic-lymphocytic-leukemiasmall-lymphocytic-lymphoma-cllsll-100590453","NCT06967610","Phase II Study of Combined Pirtobrutinib, Venetoclax and Obinutuzumab (PVO) Time-limited Treatment for Patients With Recurrent Chronic Lymphocytic Leukemia\u002FSmall Lymphocytic Lymphoma (CLL\u002FSLL).","Eligibility Criteria:\n\n1. Age 18 years or older.\n2. Diagnosis of CLL\u002FSLL per 2018 iwCLL criteria (See Appendix 1).\n3. Participants with previously treated CLL requiring therapy based on 2018 iwCLL criteria.\n4. The participant is able to take oral medications.\n5. Willing and capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.\n6. Prior or ongoing therapy with covalent BTKi is allowed, but not required.\n7. Prior or ongoing therapy (at least for six months) with BCL2i is allowed, but not required. Prior therapy with combined BTKi and BCL2i or triplet BTKi, BCL2 and anti-CD20 mAb is allowed, but Participants need to be at least six months after completion of combination therapy. Participants with history of prior venetoclax therapy should have achieved at least a partial response or better while receiving venetoclax therapy.\n8. Participants are required to have the following washout periods prior to planned Cycle 1 Day1 (C1D1).\n\n   * Targeted agents, investigational agents, therapeutic monoclonal antibodies or cytotoxic chemotherapy: 5 half-lives or 2 weeks, whichever is shorter\n   * immunoconjugated antibody treatment within 10 weeks\n   * broad field radiation (≥ 30% of the bone marrow or whole brain radiotherapy) must be completed 14 days prior to enrollment\n   * palliative limited field radiation must be completed 7 days prior to enrollment\n9. Prior treatment-related AEs must have recovered to Grade ≤ 1 with the exception of alopecia and Grade 2 peripheral neuropathy.\n10. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.\n11. Participants must have adequate renal and hepatic function:\n\n    * Serum bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for Participants with Gilbert's disease or disease involvement by CLL\u002FSLL.\n    * Serum creatinine clearance of ≥30ml\u002Fmin (calculated or measured).\n    * ALT and AST ≤3.0 x ULN, unless clearly due to documented disease involvement, in which case ALT and AST ≤5.0 x ULN\n12. Adequate bone marrow function:\n\n    * Platelet count of ≥50,000\u002Fμl, with no platelet transfusion in prior 2 weeks.\n    * ANC ≥750\u002Fμl in the absence of growth factor support within 7 days of screening assessment.\n    * Hemoglobin ≥8g\u002FdL, independent of transfusions within 7 days of screening assessment. Please refer to Appendix 4 for details of adjustments of toxicities in participants with abnormal baseline values)\n13. Adequate coagulation, defined as activated partial thromboplastin time (aPTT) or partial thromboplastin time and prothrombin time (PT) or international normalized ratio (INR) not greater than 1.5 x ULN.\n14. Women of childbearing potential must have a negative serum beta human chorionic gonadotropin (β-hCG) pregnancy test result at the time of screening and serum or urine β-hCG pregnancy test within 7 days prior to the first dose of study drugs and must agree to use both a highly effective method of birth control (eg, implants, injectables, combined oral contraceptives, some intrauterine devices \\[IUDs\\], complete abstinence, or sterilized partner) and a barrier method (eg., condoms, vaginal ring, sponge, etc) during the period of therapy and for 6 months after the last dose of study drug (pirtobrutinib and Obinutuzumab) and 12 months after the last dose of obinutuzumab. Women of nonchildbearing potential are those who are postmenopausal (defined as absence of menses for ≥1 year) or who have had a bilateral tubal ligation or hysterectomy. Men who have partners of childbearing potential must agree to use effective contraception, defined above, during the study and for 30 days following the last dose of study drug\n\nExclusion Criteria:\n\n1. Participants who experienced progression of disease according to 2018 iwCLL criteria while on venetoclax will be excluded.\n2. Patient with prior history of Richter's syndrome or current Richter's Syndrome.\n3. Participants with known hypersensitivity to any of the excipients of pirtobrutinib, venetoclax,obinutuzumab or to any intended study medications.\n4. Known or suspected history of central nervous system (CNS) involvement by CLL\u002FSLL.\n5. History of bleeding diathesis.\n6. Participants who experienced a major bleeding event on a prior BTK inhibitor.• NOTE: Major bleeding is defined as bleeding having one or more of the following features: life-threatening bleeding with signs or symptoms of hemodynamic compromise; bleeding associated with a decrease in the hemoglobin level of at least 2 g\u002FdL; or bleeding in a critical area or organ (e.g., retroperitoneal, intraarticular, pericardial, epidural, or intracranial bleeding or intramuscular bleeding with compartment syndrome).\n7. History of stroke or intracranial hemorrhage within 6 months of enrollment.\n8. Participants requiring therapeutic anticoagulation with warfarin or another vitamin K antagonists.\n9. Major surgery within 4 weeks of planned start of study therapy.\n10. A significant history of renal, neurologic, psychiatric, endocrine, metabolic or immunologic disorder, that, in the opinion of the Investigator, would adversely affect the participant's participation in this study or interpretation of study outcomes.\n11. History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor-modified Tcell (CAR-T) therapy within 60 days of enrollment or presence of any of the following, regardless of prior SCT and\u002For CAR-T therapy timing:\n\n    * active graft versus host disease (GVHD);\n    * cytopenia from incomplete blood cell count recovery post-transplant;\n    * need for anti-cytokine therapy for toxicity from CAR-T therapy; residual symptoms of neurotoxicity \\> Grade 1 from CAR-T therapy;\n    * ongoing immunosuppressive therapy (\\> 20 mg prednisone or equivalent daily).\n12. Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia \\[AIHA\\], idiopathic thrombocytopenic purpura \\[ITP\\]) for which new therapy was introduced or existing therapy was escalated within the 4 weeks prior to study enrollment to maintain adequate blood counts.\n13. Participants who experienced grade \\>3 arrhythmia on prior treatment with BTK inhibitor.\n14. Significant cardiovascular disease, defined as any of the following:\n\n    1. Unstable angina or acute coronary syndrome within the past 2 months.\n    2. History of myocardial infarction within 6 months prior to planned start of study treatment.\n    3. Documented left ventricular ejection fraction (LVEF) by any method of ≤ 45% in the 12 months prior to planned start of study treatment.\n    4. ≥ Grade 3 New York Heart Association (NYHA) functional classification system of heart failure.\n    5. uncontrolled or symptomatic arrhythmias\n15. Prolongation of the QT interval corrected (QTc - see Appendix 3) for heart rate using Fredericia's Formula (QTcF) \\> 470 msec on an EKG during screening.\n\n    1. QTcF is calculated using Fredericia's Formula (QTcF = QT\u002F(RR\\^0.33)\n    2. Correction of suspected drug-induced QTcF prolongation or prolongation due to electrolyte abnormalities can be attempted at the Investigator's discretion, and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug not known to be associated with QTcF prolongation or electrolyte supplementation.\n    3. Correction of QTc for underlying bundle branch block (BBB) permissible. Participants with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker\n16. Hepatitis B or hepatitis C testing indicating active\u002Fongoing infection based on screening laboratory tests as defined as:\n\n    1. Hepatitis B virus (HBV): Participants with positive hepatitis B surface antigen (HBsAg) are excluded. Participants with positive hepatitis B core antibody (anti-HBc) and negative HBsAg require hepatitis B polymerase chain reaction (PCR) evaluation. Participants who are hepatitis B PCR positive will be excluded.\n    2. Hepatitis C virus (HCV): positive hepatitis C antibody. If positive hepatitis C antibody result, participant will need to have a negative result for hepatitis C ribonucleic acid (RNA) . Participants who are hepatitis C RNA positive will be excluded.\n17. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, parasitic or fungal) or other clinically significant active disease process which in the opinion of the Principal Investigator may pose a risk for patient participation. Screening for chronic conditions is not required.\n18. Known Human Immunodeficiency Virus (HIV) infection, regardless of CD4 count. For participants with unknown HIV status, HIV testing will be performed at screening and result must be negative for enrollment.\n19. Known active CMV infection. Participants with unknown or negative status are eligible.\n20. Vaccination with live vaccine within 28 days prior to enrollment\n21. Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of the oral administered study treatments.\n22. Active other malignancy unless in remission and with life expectancy \\> 2 years. with exception of participants diagnosed with basal cell or squamous cell carcinoma of the skin or carcinoma \"in situ\" of the cervix or breast who are eligible even if diagnosed within 2 years. If Participants have another malignancy that was treated within the last 2 years, such participants may be enrolled, if the likelihood of requiring systemic therapy for this other malignancy within 2 years is less than 10%, as determined by an expert in that particular malignancy at MD Anderson Cancer Center, and after consultation with the Principal Investigator.\n23. Current treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers. A washout period of at least 5 half-lives of these agents following discontinuation before study entry is required (treatment with moderate CYP3A4 inhibitors or inducers is not excluded). Because of their effect on CYP3A4, use of any of the following within 7 days of study therapy start or planned use during study participation is prohibited i. Grapefruit or grapefruit products ii. Seville oranges or products from Seville oranges iii. Star fruit.\n24. Current treatment with the following P-gp inhibitors: amiodarone, clarithromycin, cyclosporine, erythromycin, ketoconazole, and verapamil. A washout period of at least 5 half-lives of the inhibitor before study entry is required.\n25. Participants that are pregnant or plan to become pregnant during the study or within 1 month of the last dose of study treatment.\n\n25\\) Participants that are lactating or plan to breastfeed during the study or within 1 week of the last dose of study treatment.",{"count":53,"type":20},40,[23],"To learn if the drug combination pirtobrutinib, venetoclax, and obinutuzumab can help to control relapsed CLL\u002FSLL.",[57,27],"Chronic Lymphocytic Leukemia","2025-11-05",{"date":60,"type":37},"2025-11-06",{"date":62,"type":37},"2025-07-15",{"date":64,"type":20},"2033-06-01",{"name":66,"class":44},"M.D. Anderson Cancer Center",1]