Actively Recruiting
Phase II Study of Acalabrutinib, Venetoclax, and Durvalumab Combination Therapy in Patients With Richter Transformation From Chronic Lymphocytic Leukemia
Led by Mayo Clinic · Updated on 2026-03-25
27
Participants Needed
3
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating a combination therapy of acalabrutinib, venetoclax, and durvalumab to treat patients with Richter transformation, a rare condition where chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) changes into a fast-growing lymphoma. This phase II trial aims to determine how well this treatment works and its safety, focusing on progression-free survival at 6 months and other response and survival outcomes. Participants receive acalabrutinib orally twice a day, durvalumab intravenously on day 1, and venetoclax orally once daily during 28-day cycles for up to 12 cycles if tolerated and no disease progression occurs. After this, a maintenance phase involves acalabrutinib twice daily and venetoclax daily on days 1 to 90 of each 90-day cycle for 4 cycles. Throughout the study, patients undergo blood tests, bone marrow sampling, and imaging scans such as PET/CT or CT. During the trial, researchers monitor treatment effects through clinical assessments, lab tests, and imaging to evaluate response rates, survival, and safety. Follow-up occurs 30 days after treatment ends and then every 90 days for up to 5 years. The study also collects tissue and blood samples to explore biomarkers and immune responses related to the therapy.
CONDITIONS
Brief Title
Acalabrutinib, Venetoclax and Durvalumab for the Treatment of Richter Transformation From Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older and willing to provide consent and follow-up
- Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) by established criteria
- Biopsy-proven Richter's transformation of CLL
- Measurable disease of at least 1 cm detected by PET or CT
- ECOG performance status of 0, 1, or 2
- Adequate blood counts and organ function as specified
- Negative pregnancy test for women of childbearing potential
- Willingness to use effective contraception if applicable
- Willing to provide tissue, blood, and bone marrow samples for research
- Ability to return to the enrolling institution for follow-up
You will not qualify if you...
- Uncontrolled cardiovascular disease or symptomatic arrhythmias
- Serious chronic gastrointestinal conditions with diarrhea
- History of progressive multifocal leukoencephalopathy (PML)
- Stroke or intracranial hemorrhage within 6 months prior
- Bleeding disorders such as hemophilia
- Active uncontrolled infections, including certain viral infections
- Known HIV infection
- Active hepatitis B or C infection unless treated and controlled
- Pregnancy or breastfeeding
- Unwillingness to use effective contraception
- Use of other investigational agents recently, excluding certain drugs
- Prior durvalumab treatment
- Active or recent uncontrolled autoimmune or inflammatory disorders
- Interstitial lung disease or active pneumonitis
- Psychiatric or substance abuse disorders interfering with trial requirements
- Active central nervous system lymphoma requiring therapy
- Recent allogeneic stem cell transplant or chronic graft versus host disease
- Use of strong CYP3A inhibitors or proton pump inhibitors not switchable
- History of other primary malignancies with exceptions
- Recent immunosuppressive medications except certain exceptions
- Recent radiation therapy or major surgery
- Body weight less than or equal to 30 kg
- Life expectancy less than 12 weeks
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.
screening and enrollment visit
Duration - 12 cycles of 28 days each
Participants receive a combination therapy of acalabrutinib taken orally twice daily, durvalumab given intravenously on day 1, and venetoclax taken orally once daily in 28-day cycles. This treatment repeats for up to 12 cycles unless the disease progresses or unacceptable side effects occur.
Monthly visits for up to 12 cycles
Duration - 4 cycles of 90 days each
Participants receive maintenance therapy with acalabrutinib orally twice daily and venetoclax orally once daily on days 1 to 90 of each cycle. This repeats every 90 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
Visits every 3 months for 4 cycles
Duration - Up to 5 years after enrollment
After completing treatment, participants are monitored for safety and long-term outcomes with scheduled follow-up visits.
1 visit at 30 days post-treatment and then visits every 90 days
Trial Site Locations
Total: 3 locations
1
Stanford Cancer Institute Palo Alto
Palo Alto, California, United States, 94304
Not Yet Recruiting
2
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Actively Recruiting
3
Washington University School of Medicine
St Louis, Missouri, United States, 63110
Withdrawn
Research Team
C
Clinical Trials Referral Office
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
Similar Trials
Frequently Asked Questions
Have more questions? Get in touch with our team for quick support
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here