Actively Recruiting
A Randomized Phase II Study of Acalabrutinib and Venetoclax With or Without Early Obinutuzumab for Patients With Chronic Lymphocytic Leukemia
Led by M.D. Anderson Cancer Center · Updated on 2026-04-14
168
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
Sponsors
M
M.D. Anderson Cancer Center
Lead Sponsor
N
National Cancer Institute (NCI)
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating how well a combination of acalabrutinib and venetoclax, with or without early use of obinutuzumab, works to treat high-risk, recurrent, or treatment-resistant chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This phase II trial aims to improve the eradication of minimal residual disease in bone marrow and to assess responses in both newly diagnosed and relapsed/refractory patients using established clinical criteria. Participants are randomly assigned to one of two treatment groups. In Arm I, patients take acalabrutinib orally twice daily, add venetoclax weekly then daily starting cycle 4, and may receive obinutuzumab intravenously in later cycles if certain disease markers are present. In Arm II, obinutuzumab is given early in the treatment alongside oral acalabrutinib and venetoclax. Treatments repeat in cycles every 28 days (or 42 days for cycle 14) for up to 26 cycles, unless the disease progresses or side effects are unacceptable. Throughout the study, patients undergo disease assessments including bone marrow testing for minimal residual disease at specified cycles. Researchers monitor overall response rates, safety, drug levels in the blood, and time to disease progression. After completing treatment, participants continue periodic follow-up visits to assess long-term outcomes and responses to retreatment if relapse occurs.
CONDITIONS
Brief Title
Acalabrutinib and Venetoclax With or Without Early Obinutuzumab for the Treatment of High Risk, Recurrent, or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma with treatment indication by 2018 iwCLL criteria
- Untreated patients with high-risk features or age 65 years or older, or patients relapsed/refractory to at least one prior therapy
- Age 18 years or older
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
- Adequate kidney and liver function including bilirubin and creatinine clearance thresholds
- Absolute neutrophil count above 750 unless due to marrow infiltration
- Platelet count above 30,000/µl without recent transfusion unless due to marrow infiltration
- Women of childbearing potential must have negative pregnancy test and agree to contraception
- Men must agree to use effective contraception during and after study treatment
- Free of prior malignancies for 2 years except certain skin or cervical cancers
- Ability to provide written informed consent
You will not qualify if you...
- Prior treatment with combined BTK and BCL2 inhibitors without adequate response or progression within 2 years
- Recent major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, investigational therapy, or live virus vaccination within 3 weeks unless rapid disease progression
- Severe allergic reactions to monoclonal antibodies or murine products
- Active uncontrolled infections
- Known HIV positive status
- Active hepatitis B or C infection
- Uncontrolled autoimmune conditions requiring high-dose steroids
- Significant recent cardiovascular disease or severe heart failure
- Pregnancy or breastfeeding
- Concurrent use of warfarin
- Use of strong CYP3A inhibitors or inducers near study start and during venetoclax treatment
- Consumption of grapefruit or certain fruits before venetoclax
- Known bleeding disorders or recent stroke
- Malabsorption or inability to take oral medications
- Other severe medical or psychiatric conditions increasing risk or interfering with study participation
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
Duration - Up to 26 cycles (each cycle 28 or 42 days)
Participants receive acalabrutinib and venetoclax orally in cycles of 28 days, with obinutuzumab given intravenously at specific cycles depending on response and treatment arm. Treatment lasts up to 26 cycles (approximately 1 to 2 years) unless disease progression or unacceptable toxicity occurs.
Repeated visits every 28 days (or 42 days for cycle 14) during treatment cycles
Duration - Duration not specified
After completing treatment, participants are followed up periodically to monitor their health and disease status.
Trial Site Locations
Total: 1 location
1
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
Research Team
W
William G Wierda
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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