Acalabrutinib in Combination With Venetoclax or Obinutuzumab for the Treatment of Treatment-naive Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia Clinical Trial

Official title: Prospective Randomized Phase II Study of Acalabrutinib + Obinutuzumab or Venetoclax in Previously Untreated CLL

Status Recruiting

Clinical Trial Summary

This phase II trial tests whether acalabrutinib in combination with venetoclax or obinutuzumab works to shrink tumors in patients with treatment-naive chronic lymphocytic leukemia . Acalabrutinib is also an inhibitor that works in the body to block the activation of certain cells that lead to the growth of cancerous B cells. 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. Obinutuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving acalabrutinib in combination with venetoclax or obinutuzumab may help ease symptoms, decrease the amount of cancer suggestive of improvement, prolonged disease-free remission and/or survival, and increased knowledge about cancer treatment in patients with chronic lymphocytic leukemia. Patients will be treated with acalabrutinib for 12 cycles, and then randomized to receive 6 cycles of acalabrutinib plus obinutuzumab or acalabrutinib plus venetoclax.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To evaluate whether the addition of venetoclax or obinutuzumab for 6 cycles to patients receiving acalabrutinib for 1 year in treatment-naive (TN) chronic lymphocytic leukemia (CLL) will improve rate of bone marrow (BM) undetectable minimal residual disease (uMRD).

SECONDARY OBJECTIVES:

I. To assess the safety and tolerability of a delayed approach to combination therapy in patients with TN CLL.

II. To determine the overall response rate (ORR) of the addition of venetoclax or obinutuzumab for 6 cycles to patients receiving acalabrutinib for 1 year in TN CLL.

III. To determine the progression free survival (PFS) of the addition of venetoclax or obinutuzumab for 6 cycles to patients receiving acalabrutinib for 1 year in TN CLL.

IV. To determine the duration of response (DOR) of the addition of venetoclax or obinutuzumab for 6 cycles to patients receiving acalabrutinib for 1 year in TN CLL.

V. To determine the time to next treatment (TTNT) of the addition of venetoclax or obinutuzumab for 6 cycles to patients receiving acalabrutinib for 1 year in TN CLL.

EXPLORATORY OBJECTIVES:

I. To determine the concordance rate between uMRD status as measured by next generation sequencing (NGS) versus standard flow cytometry as well as blood vs bone marrow, and examine implications for PFS.

II. To determine how acalabrutinib plus venetoclax or obinutuzumab changes numbers of T, B, and natural killer (NK) cells during and after therapy.

III. To determine how baseline genomic features predict outcomes following acalabrutinib plus venetoclax or obinutuzumab.

OUTLINE: Patients are randomized into 1 of 2 arms.

ARM I: Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28. Patients also receive obinutuzumab intravenously (IV) on days 1, 2, 8, and 15 of cycle 13 and day 1 of cycles 14-18. Treatment repeats every 28 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive acalabrutinib PO BID on days 1-28. Patients also receive venetoclax PO once daily (QD) on days 1-28 days of cycles 13-18. Treatment repeats every 28 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity.

After completion of the study treatment, patients are followed up at 30 days and every 6 months up to 10 years. ;

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Small Lymphocytic Lymphoma

• NCT number: NCT05336812
• Study type: Interventional
• Source: Ohio State University Comprehensive Cancer Center
• Contact: The Ohio State University Comprehensive Cancer Center
• Phone: 800-293-5066
• Email: OSUCCCClinicaltrials@osumc.edu
• Status: Recruiting
• Phase: Phase 2
• Start date: September 13, 2022
• Completion date: December 31, 2024