A Study to Evaluate the Effect of Venetoclax on Participants Receiving a Covalent Bruton's Tyrosine Kinase Inhibitor (cBTKi) for First-line Chronic Lymphocytic Leukemia (1L CLL) to Achieve Deep Durable Remissions to Allow Off-treatment Period

NCT06524375 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: ML45219
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 20

Brief Summary

The main purpose of the study is to evaluate if adding venetoclax to participants receiving cBTKi for the 1L CLL can achieve deep durable remissions of undetectable measurable residual disease \[uMRD \< or 10\^-4 in peripheral blood (PB)\] by end of combination treatment (EOCT) to allow off-treatment period. The acronym BRAVE stands for Btki Responders to Achieve deep remission (or off-treatment periods) with VEnetoclax.

Conditions

Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• uMRD4 Rate at EOCT

  uMRD4 will be assessed using next generation sequencing (NGS) (sensitivity 10\^-4) from PB.

  Cycle 12 Day 28 (Cycle length= 28 Days)

Secondary Outcomes (11)

• CR/CRi Rate at EOCT as Determined by the Investigator According to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Guidelines

  Up to approximately 12 months

• PR Rate at EOCT as Determined by the Investigator According to iwCLL Guidelines

  Up to approximately 12 months

• Overall Response Rate (ORR) at EOCT as Determined by the Investigator According to iwCLL Guidelines

  Up to approximately 12 months

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to approximately 13 months

• Number of Participants Who Withdrew Prematurely from the Study

  Up to approximately 12 months

Study Arms (1)

Venetoclax Added to cBTKi (Commercially Prescribed)

EXPERIMENTAL

Participants will receive venetoclax, orally, once daily (QD) with a starting ramp-up dose of 20 milligrams (mg) on Day 1 of Cycle 1 (cycle length= 28 days). The dose will increase weekly; thereafter, treatment will continue with venetoclax at the target dose of 400 mg, QD from Week 5 up to Day 28 of Cycle 12. Participant will discontinue from venetoclax and/or cBTKi after 12 cycles. Participants with detectable measurable residual disease with the presence of less than 1 CLL cell in 10,000 leukocytes (\< 10\^-4) (MRD4) or uMRD4 with partial response (PR) may continue receiving cBTKi-monotherapy (i.e. ibrutinib or acalabrutinib, or zanubrutinib) as previously prescribed by the investigator according to the prescribing label.

Drug: Venetoclax; Drug: cBTKi Monotherapy

Interventions

Venetoclax DRUG

Venetoclax tablets will be administered as per the schedule specified in the arm.

Also known as: RO5537382

Venetoclax Added to cBTKi (Commercially Prescribed)

cBTKi Monotherapy DRUG

Commercially available cBTKi (ibrutinib or acalabrutinib, or zanubrutinib) will be administered in accordance with its prescribing label.

Venetoclax Added to cBTKi (Commercially Prescribed)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with CLL and currently receiving a stable dose of cBTKi (i.e., ibrutinib, acalabrutinib, or zanubrutinib) for at least 6 months for 1L treatment with a response of at least a PR per iwCLL criteria
• Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to (\</=) 2
• Adequate renal and liver function

You may not qualify if:

• Prior B-cell lymphoma (Bcl-2) inhibitor therapy
• Anti-cluster of differentiation 20 (CD20) therapy within the month prior to screening
• Progressive or stable disease on cBTKi
• Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (Richter's transformation or pro-lymphocytic leukemia)
• History of cardiomyopathy
• Hypersensitivity to venetoclax or to any of the excipients (e.g., trehalose)
• Clinically significant cardiovascular disease
• Active bleeding or history of bleeding diathesis
• Pregnant women and nursing mothers
• Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (20)

Highlands Oncology Group

Springdale, Arkansas, 72762, United States

Location

Rocky Mountain Cancer Centers (Aurora) - USOR

Aurora, Colorado, 80012-5405, United States

Location

Cancer Specialists of North Florida

Jacksonville, Florida, 32256-6932, United States

Location

Fort Wayne Medical Oncology and Hematology, Inc

Fort Wayne, Indiana, 46804, United States

Location

Mission Blood and Cancer - MercyOne Cancer Center

Des Moines, Iowa, 50314-3030, United States

Location

American Oncology Partners of Maryland, PA

Bethesda, Maryland, 20817-1915, United States

Location

Dana-Farber Cancer Institute - Hematologic Oncology Treatment Center

Boston, Massachusetts, 02215-5418, United States

Location

Nebraska Cancer Specialists St Francis - Grand Island

Grand Island, Nebraska, 68803, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68130-2042, United States

Location

Astera Cancer Care East Brunswick

East Brunswick, New Jersey, 08816-4096, United States

Location

San Juan Oncology Associates, PC

Farmington, New Mexico, 87401, United States

Location

Oncology Hematology Care Inc - Cincinnati - USOR

Cincinnati, Ohio, 45236-2725, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Willamette Valley Cancer Institute and Research Center

Eugene, Oregon, 97401-6043, United States

Location

Asante Rogue Regional Medical Center

Medford, Oregon, 97504-8332, United States

Location

Tennessee Oncology, PLLC - Chattanooga

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology - Midtown

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Oncology- Northeast Texas

Tyler, Texas, 75702, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

venetoclax

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2024
• First Posted: July 29, 2024
• Study Start: August 9, 2024
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): January 31, 2030
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (20)