A Phase 2 interventional study of Atezolizumab and Laboratory Biomarker Analysis in Chronic Lymphocytic Leukemia, Recurrent Transformed Chronic Lymphocytic Leukemia and Refractory Transformed Chronic Lymphocytic Leukemia, sponsored by M.D. Anderson Cancer Center. Active, not recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-10.
Sponsored by M.D. Anderson Cancer Center · Phase 2, Interventional, and Treatment
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.
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.
1,603 studies on the registry are indexed under Leukemia, Lymphocytic, Chronic, B-Cell; 243 are open to participants now.
This study's enrollment of 50 is above the median of 40 across 1,325 interventional studies indexed under Leukemia, Lymphocytic, Chronic, B-Cell.
Browse Leukemia, Lymphocytic, Chronic, B-Cell studies →M.D. Anderson Cancer Center is the lead sponsor of 2,999 studies on the registry; 581 are open to participants now.
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Exclusion:
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.
Drug: Atezolizumab · Other: Laboratory Biomarker Analysis · Biological: Obinutuzumab · Drug: 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.
Drug: Atezolizumab · Other: Laboratory Biomarker Analysis · Biological: Obinutuzumab · Drug: Venetoclax
Given IV
Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq
Correlative studies
Given IV
Also known as: Anti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva, huMAB(CD20), R7159, RO 5072759, RO-5072759, RO5072759
Given PO
Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto
Minimal residual disease (MRD) negative rate (Cohort I)
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.
Time frame: At end of cycle 9
Incidence of adverse events (AEs)
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.
Time frame: Up to 1 year
Best overall response
Will be estimated along with the 95% credible interval.
Time frame: Up to 14 cycles (cohort 1) or 26 cycles (cohort 2)
Complete response rate
Summary statistics will be provided for continuous variables. Frequency tables will be used to summarize categorical variables.
Time frame: Up to 1 year
Duration of response
Summary statistics will be provided for continuous variables. Frequency tables will be used to summarize categorical variables.
Time frame: Up to 1 year
Progression-free survival
Kaplan-Meier method will be used.
Time frame: Up to 1 year
Overall survival
Kaplan-Meier method will be used.
Time frame: Up to 1 year
Change in immunological and molecular features
Will determine if the change in immunological and molecular features will correlate with patient outcomes and will be assessed through fitting linear or non-linear mixed effect models.
Time frame: Baseline up to 1 year
This study is active, not recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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Leukemia, Lymphocytic, Chronic, B-Cell→
M.D. Anderson Cancer Center