NCT05388006

Acalabrutinib, Venetoclax and Durvalumab for the Treatment of Richter Transformation From Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

MC198B, Phase II Study of a Combination Therapy of Acalabrutinib, Venetoclax and Durvalumab in Patients With Richter Transformation From Chronic Lymphocytic Leukemia (CLL)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 27 (estimated)
• Sponsor: Mayo Clinic · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests whether acalabrutinib, venetoclax, and durvalumab work in treating patients with Richter transformation from chronic lymphocytic leukemia or small lymphocytic lymphoma. Richter transformation is a rare condition in which chronic lymphocytic leukemia or small lymphocytic lymphoma changes into a fast-growing type of lymphoma. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving acalabrutinib, venetoclax, and durvalumab may help improve survival in patients with Richter transformation.

Detailed description

PRIMARY OBJECTIVE: I. Determine the progression free survival (PFS) at 6 months of the combination therapy of acalabrutinib, venetoclax, and durvalumab in patients with Richter transformation from chronic lymphocytic leukemia (CLL). SECONDARY OBJECTIVES: I. Determine the safety of the combination therapy of acalabrutinib, venetoclax and durvalumab in patients with Richter transformation from CLL. II. Evaluate the overall response rate (ORR), complete response (CR) rate, and partial response (PR) rate of the above combination therapy. III. Overall survival, PFS, and treatment free survival of this above combination therapy. CORRELATIVE RESEARCH OBJECTIVES: I. Determine the biomarkers that predict clinical response of this above combination therapy. II. Determine the immune profiles of patients while receiving this combination of therapy. OUTLINE: Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28, durvalumab intravenously (IV) over 1 hour on day 1, and venetoclax PO once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive acalabrutinib PO BID and venetoclax PO QD on days 1-90 of each cycle. Cycles repeat every 90 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, bone marrow aspiration and biopsy, and positron emission tomography (PET)/computed tomography (CT) or CT throughout the study. After completion of study treatment, patients are followed up at 30 days and then every 90 days until 5 years from study enrollment.

Conditions

• Chronic Lymphocytic Leukemia
• Richter Syndrome
• Small Lymphocytic Lymphoma

Interventions

Type	Name	Description
DRUG	Acalabrutinib	Given PO
BIOLOGICAL	Durvalumab	Given IV
DRUG	Venetoclax	Given PO
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy
PROCEDURE	Positron Emission Tomography (PET)	Undergo PET/CT
PROCEDURE	Computed Tomography	Undergo PET/CT or CT

Timeline

• Start date: 2023-01-05
• Primary completion: 2027-02-22
• Completion: 2027-02-22
• First posted: 2022-05-24
• Last updated: 2026-03-25

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study