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Protocol No. A041702

Principal Investigator Fletcher, Christopher

Phase III

Age Group Adult

Scope National

Sponsor Type National

Title A Randomized Phase III Study of Ibrutinib plus Obinutuzumab versus Ibrutinib plus Venetoclax and Obinutuzmab in Untreated Older Patients (>/= 70 YEARS OF AGE) with Chronic Lymphocytic Leukemia (CLL)

Objective The purpose of this study is to compare the usual treatment alone (ibrutinib plus obinutuzumab) to using venetoclax plus the usual treatment. The addition of venetoclax to the usual treatment could prevent your chronic lymphocytic leukemia from returning. But, it could also cause side effects, which are described in the risks section. The study will also see if patients who receive ibrutinib plus obinutuzumab plus venetoclax and have no detectable chronic lymphocytic leukemia after 1 year of treatment, can stop taking ibrutinib

Treatment
Group 1: ibrutinib orally once a day for 15 cycles. You will receive intravenous infusion of obinutuzumab on days 1, 2, 8, and 15 during Cycle 1, and then on day 1 of cycles 2-6. Each cycle lasts 28 days. Cycle 15, CT scans will be performed, and a bone marrow aspirate and blood will be collected. To see if you have detectable amounts of CLL
Group 2: venetoclax plus the usual drugs (ibrutinib and obinutuzumab). You will receive intravenous infusion of obinutuzumab on days 1,2,8, and 15 during Cycle 1, and then on day 1 of cycles 2-6. You will take ibrutinib pills orally once a day for 15 cycles. You will take venetoclax by mouth once a day starting on Cycle 3 Day 1 until the end of Cycle 14. Cycle 15, CT scans will be performed, a bone marrow aspirate and blood will be collected to see if you have detectable amounts of CLL.. If you still have detectable CLL, you will then go on to take ibrutinib pills by mouth once a day until your disease gets worse or your side effects become severe

Description A Randomized Phase III Study of Ibrutinib Plus Obinituzumab Versus Ibrutinib Plus Venetoclax and Obinutuzumab in Untreated Older Patients(greater than or equal to 70 years of age) with Chronic Lymphocytic Leukemia(CLL)

Key Eligibility
Pre-registration eligibility criteria:
  • Must have been diagnosed with CLL and have greater than 5000 B-cells per uL of peripheral blood at any point during the course of their disease
  • Central FISH blood submission
  • Must be diagnosed with CLL in accordance with 2018 IWCLL criteria as defined by the protocol
  • Must be intermediate or high-risk Rai stage CLL as defined by the protocol
  • Must meet criteria for treatment as defined by 2018 IWCLL guidelines as defined by the protocol
  • Must not have had prior therapy for CLL (except palliative steroids or treatment of autoimmune complications of CLL with rituximab or steroids)
  • Treatment with rituximab and/or high dose corticosteroids for autoimmune complications of CLL must be complete at least 4 weeks prior to enrollment. Palliative steroids must be at a dose not higher than 20 mg/day of prednisone or equivalent corticosteroid at the time of registration
  • 70 years of age or older
  • ECOG performance status 0-2
  • Adequate hematologic, renal and hepatic function as defined by the protocol
  • Comorbid conditions or other active diseases
  • Must not have any history of Richter’s transformation or prolymphocytic leukemia (prolymphocytes in blood greater than 55%)
  • Chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated
  • History of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load
  • Class III or Class IV heart failure by New York Heart Association, those with unstable angina, and those with uncontrolled arrhythmia are not eligible
  • Myocardial infarction, intracranial bleed, or stroke within the past 6 months are not eligible
  • Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • Must not be receiving active systemic anticoagulation with heparin or warfarin. Patients on warfarin must discontinue the drug for at least 10 days prior to registration on the study
  • Chronic concomitant treatment with strong inhibitors of CYP3A4/5 is not allowed on this study, Chronic concomitant treatment with strong CYP3A4/5 inducers is not allowed
  • Must not require more than 20 mg prednisone or equivalent corticosteroid daily
  • Must not have uncontrolled active systemic infection requiring intravenous antibiotics
  • Central FISH blood results are mandatory prior to registration/randomization for it will be used for stratification
  • Must be able to swallow capsules and not have the following conditions: disease significantly affecting gastrointestinal absorption, resection of the stomach or small bowel, partial or complete bowel obstruction
  • Must be able to receive either a xanthine oxidase inhibitor or rasburicase for prophylaxis/treatment of TLS
  • Must not have a known allergy to mannitol
  • Must not have prior significant hypersensitivity to rituximab (not including infusion reactions)

  • Applicable Disease Sites Leukemia

    Status Open

    Participating Institutions Dean Health System, Hematology and Oncology Clinic ; UW Hospital and Clinics; UWCCC 1 South Park