Atezolizumab, Obinutuzumab, and Venetoclax in Treating Patients With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Relapsed or Refractory Richter Syndrome
- Conditions
- Refractory Transformed Chronic Lymphocytic LeukemiaChronic Lymphocytic LeukemiaRecurrent Transformed Chronic Lymphocytic LeukemiaSmall Lymphocytic LymphomaRichter Syndrome
- Interventions
- Registration Number
- NCT02846623
- Lead Sponsor
- M.D. Anderson Cancer Center
- Brief Summary
This phase II trial studies how well atezolizumab, obinutuzumab, and venetoclax work in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma or Richter syndrome that has come back (recurrent) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as atezolizumab and obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as venetoclax, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving atezolizumab, obinutuzumab, and venetoclax may work better in treating patients with chronic lymphocytic leukemia, small lymphocytic lymphoma, or Richter syndrome.
- Detailed Description
PRIMARY OBJECTIVES:
I. To determine the efficacy of atezolizumab in combination with obinutuzumab and venetoclax in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)/Richter transformation (RT).
SECONDARY OBJECTIVES:
I. To determine the safety of atezolizumab combined with obinutuzumab and venetoclax in patients with CLL/SLL/RT.
II. To determine overall response rate (ORR), complete response rate (CR), duration of response (DOR), and minimal residual disease (MRD) negative remission rate.
III. To determine the progression-free survival (PFS). IV. To determine the overall survival (OS).
EXPLORATORY OBJECTIVES:
I. To determine immunological and molecular features, at baseline and/or that change with treatment, that correlate with outcomes in patients treated with atezolizumab combined with obinutuzumab and venetoclax.
OUTLINE: Patients are assigned to 1 of 2 cohorts.
COHORT I: Patients receive obinutuzumab intravenously (IV) over 4-6 hours on days 1, 2, 8, and 15 of cycle 1 and on day 1 of cycles 2-9 and atezolizumab IV over 30-60 minutes on days 3-4 of cycle 1 and on days 1-2 of cycles 2-9. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 3, patients also receive venetoclax orally (PO) on days 1-28. Treatment repeats every 28 days for 14 cycles in the absence of disease progression or unacceptable toxicity.
COHORT II: Patients receive obinutuzumab intravenously IV over 4-6 hours on days 1, 2, 8, and 15 of cycle 1 and on day 1 of cycles 2-9 and atezolizumab IV over 30-60 minutes on days 3-4 of cycle 1 and on days 1-2 of cycles 2-9. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 2, patients receive venetoclax PO on days 1-28. Treatment repeats every 28 days for 25 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 1 year.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 65
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort II (obinutuzumab, atezolizumab, venetoclax) Laboratory Biomarker Analysis Patients receive obinutuzumab intravenously IV over 4-6 hours on days 1, 2, 8, and 15 of cycle 1 and on day 1 of cycles 2-9 and atezolizumab IV over 30-60 minutes on days 3-4 of cycle 1 and on days 1-2 of cycles 2-9. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 2, patients receive venetoclax PO on days 1-28. Treatment repeats every 28 days for 25 cycles in the absence of disease progression or unacceptable toxicity. Cohort I (obinutuzumab, atezolizumab, venetoclax) Laboratory Biomarker Analysis Patients receive obinutuzumab IV over 4-6 hours on days 1, 2, 8, and 15 of cycle 1 and on day 1 of cycles 2-9 and atezolizumab IV over 30-60 minutes on days 3-4 of cycle 1 and on days 1-2 of cycles 2-9. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 3, patients also receive venetoclax PO on days 1-28. Treatment repeats every 28 days for 14 cycles in the absence of disease progression or unacceptable toxicity. Cohort I (obinutuzumab, atezolizumab, venetoclax) Atezolizumab Patients receive obinutuzumab IV over 4-6 hours on days 1, 2, 8, and 15 of cycle 1 and on day 1 of cycles 2-9 and atezolizumab IV over 30-60 minutes on days 3-4 of cycle 1 and on days 1-2 of cycles 2-9. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 3, patients also receive venetoclax PO on days 1-28. Treatment repeats every 28 days for 14 cycles in the absence of disease progression or unacceptable toxicity. Cohort I (obinutuzumab, atezolizumab, venetoclax) Venetoclax Patients receive obinutuzumab IV over 4-6 hours on days 1, 2, 8, and 15 of cycle 1 and on day 1 of cycles 2-9 and atezolizumab IV over 30-60 minutes on days 3-4 of cycle 1 and on days 1-2 of cycles 2-9. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 3, patients also receive venetoclax PO on days 1-28. Treatment repeats every 28 days for 14 cycles in the absence of disease progression or unacceptable toxicity. Cohort II (obinutuzumab, atezolizumab, venetoclax) Atezolizumab Patients receive obinutuzumab intravenously IV over 4-6 hours on days 1, 2, 8, and 15 of cycle 1 and on day 1 of cycles 2-9 and atezolizumab IV over 30-60 minutes on days 3-4 of cycle 1 and on days 1-2 of cycles 2-9. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 2, patients receive venetoclax PO on days 1-28. Treatment repeats every 28 days for 25 cycles in the absence of disease progression or unacceptable toxicity. Cohort II (obinutuzumab, atezolizumab, venetoclax) Venetoclax Patients receive obinutuzumab intravenously IV over 4-6 hours on days 1, 2, 8, and 15 of cycle 1 and on day 1 of cycles 2-9 and atezolizumab IV over 30-60 minutes on days 3-4 of cycle 1 and on days 1-2 of cycles 2-9. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 2, patients receive venetoclax PO on days 1-28. Treatment repeats every 28 days for 25 cycles in the absence of disease progression or unacceptable toxicity. Cohort I (obinutuzumab, atezolizumab, venetoclax) Obinutuzumab Patients receive obinutuzumab IV over 4-6 hours on days 1, 2, 8, and 15 of cycle 1 and on day 1 of cycles 2-9 and atezolizumab IV over 30-60 minutes on days 3-4 of cycle 1 and on days 1-2 of cycles 2-9. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 3, patients also receive venetoclax PO on days 1-28. Treatment repeats every 28 days for 14 cycles in the absence of disease progression or unacceptable toxicity. Cohort II (obinutuzumab, atezolizumab, venetoclax) Obinutuzumab Patients receive obinutuzumab intravenously IV over 4-6 hours on days 1, 2, 8, and 15 of cycle 1 and on day 1 of cycles 2-9 and atezolizumab IV over 30-60 minutes on days 3-4 of cycle 1 and on days 1-2 of cycles 2-9. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 2, patients receive venetoclax PO on days 1-28. Treatment repeats every 28 days for 25 cycles in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Minimal residual disease (MRD) negative rate (Cohort I) At end of cycle 9 The Bayesian approach of Thall, Simon, Estey will be implemented for the toxicity and futility monitoring. Toxicity is defined as any grade 3 or higher non-hematological toxicity which is at least possibly related to the treatment. The MRD negative rate will be estimated along with the 95% credible interval for cohorts 1 and 2.
- Secondary Outcome Measures
Name Time Method Best overall response Up to 14 cycles (cohort 1) or 26 cycles (cohort 2) Will be estimated along with the 95% credible interval.
Incidence of adverse events (AEs) Up to 1 year Will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Safety data will be summarized by category, severity and frequency. The proportion of patients with AEs will be estimated, along with the Bayesian 95% credible interval.
Duration of response Up to 1 year Summary statistics will be provided for continuous variables. Frequency tables will be used to summarize categorical variables.
Overall survival Up to 1 year Kaplan-Meier method will be used.
Complete response rate Up to 1 year Summary statistics will be provided for continuous variables. Frequency tables will be used to summarize categorical variables.
Progression-free survival Up to 1 year Kaplan-Meier method will be used.
Trial Locations
- Locations (1)
M D Anderson Cancer Center
šŗšøHouston, Texas, United States