Actively Recruiting
Acalabrutinib in Combination With Venetoclax for Previously Treated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Led by Fred Hutchinson Cancer Center ยท Updated on 2026-05-18
20
Participants Needed
1
Research Sites
208 weeks
Total Duration
On this page
Sponsors
F
Fred Hutchinson Cancer Center
Lead Sponsor
A
AstraZeneca
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the combination of acalabrutinib and venetoclax in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that has not responded to previous treatments or has returned. This phase II trial aims to study how these drugs may stop cancer cell growth by targeting different pathways. Acalabrutinib blocks enzymes needed for cancer cell growth, while venetoclax works by killing cancer cells or stopping them from dividing or spreading. Participants take acalabrutinib orally twice daily for the first three 28-day cycles. Starting with the fourth cycle, venetoclax is added once daily, and this combined treatment continues every 28 days for up to 26 cycles, unless the disease progresses or side effects become unacceptable. During the study, patients undergo blood tests, bone marrow aspiration and biopsy, and imaging scans such as CT or MRI to monitor their condition. After finishing the treatment phase, patients are followed up every 12 weeks and then annually for up to 10 years to assess long-term effects. Researchers measure the rate of undetectable measurable residual disease at the end of treatment as the primary outcome. Secondary outcomes include response rates, progression-free and overall survival, and treatment toxicity. Participants will be regularly evaluated through clinical assessments and laboratory tests throughout the study duration.
CONDITIONS
Brief Title
Acalabrutinib in Combination With Venetoclax for the Treatment of Refractory or Recurrent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma, The AVENUE-2 Trial
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Men and women 18 years of age or older
- Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) meeting standard criteria
- Active disease requiring treatment with at least one of the following: progressive marrow failure, large or progressive spleen, large or symptomatic lymph nodes, progressive lymphocytosis, or constitutional symptoms
- Relapsed or refractory to at least one prior systemic therapy for CLL/SLL
- Absolute neutrophil count (ANC) of at least 750 cells/microliter or 500 if bone marrow involvement
- Hemoglobin level of 10 g/dL or higher
- Platelet count of at least 50,000 cells/microliter or 25,000 if bone marrow involvement
- Liver enzymes AST and ALT less than or equal to 2.5 times the upper limit of normal
- Total bilirubin less than or equal to 2 times the upper limit of normal unless due to Gilbert's syndrome
- Estimated creatinine clearance of 50 mL/min or higher
- ECOG performance status of 0 to 2
- Women of childbearing potential must use effective contraception during and for 30 days after treatment
- Ability to swallow capsules or tablets without difficulty
- Ability to understand and provide informed consent
You will not qualify if you...
- Known or suspected prolymphocytic leukemia or Richter's transformation
- Disease progression while on BTK inhibitor or venetoclax
- Prior intolerance to acalabrutinib or venetoclax
- Other active malignancies requiring treatment or recent cancer history within 2 years
- Significant cardiovascular disease or uncontrolled arrhythmias
- Gastrointestinal conditions affecting drug absorption or recent bowel surgery with absorption issues
- Known allergy to acalabrutinib or venetoclax
- Active bleeding disorders or use of certain blood thinners
- Abnormal blood clotting tests exceeding twice the normal limit
- Uncontrolled autoimmune blood disorders
- Recent gastrointestinal ulcers
- Use of strong CYP3A4 inhibitors or inducers near treatment start
- Use of proton pump inhibitors if receiving capsule formulation of acalabrutinib
- Recent stroke or intracranial hemorrhage
- Major surgery within 7 days before treatment
- Positive hepatitis B or C infection by PCR
- Breastfeeding or pregnant
- Participation in another therapeutic clinical trial
- HIV infection or any active serious infection
- Central nervous system involvement with CLL
- History of progressive multifocal leukoencephalopathy (PML)
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.
1 visit (in-person)
Duration - Up to 26 cycles of 28 days each
Participants receive acalabrutinib orally twice a day for the first three 28-day cycles. Venetoclax is added once daily starting with Cycle 4. Treatment repeats every 28 days for up to 26 cycles unless there is disease progression or unacceptable toxicity. Participants undergo blood sample collection, bone marrow aspiration and biopsy, and CT or MRI scans throughout treatment.
Monthly visits every 28 days for up to 26 cycles
Duration - Up to 10 years
After completing treatment, participants are followed up every 12 weeks and then annually for 10 years to monitor health and disease status.
Quarterly visits initially, then annual visits for long-term follow-up
Trial Site Locations
Total: 1 location
1
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Actively Recruiting
Research Team
M
Mazyar Shadman
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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