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NCT Number: NCT06524375

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Highlands Oncology Group, Springdale, Arkansas, United States

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

Venetoclax

Drug

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

Other names: RO5537382

cBTKi Monotherapy

Drug

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

Primary outcomes

  1. uMRD4 Rate at EOCT

    Time frame: Cycle 12 Day 28 (Cycle length= 28 Days)

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

Secondary outcomes

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

    Time frame: Up to approximately 12 months

    Complete response (CR)/complete response with incomplete recovery of the bone marrow (CRi) rate is defined as the percentage of participants with a CR or CRi at EOCT, as determined by the investigator according to the iwCLL.

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

    Time frame: Up to approximately 12 months

    PR rate is defined as the percentage of participants with a PR at EOCT, as determined by the investigator according to the iwCLL.

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

    Time frame: Up to approximately 12 months

    ORR is defined as the percentage of participants with a CR/CRi or PR at EOCT, as determined by the investigator according to the iwCLL.

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

    Time frame: Up to approximately 13 months

    AE and SAEs will be collected as part of this study at baseline and every clinical visit, until 30 days after the final dose of study treatment.

  5. Number of Participants Who Withdrew Prematurely from the Study

    Time frame: Up to approximately 12 months

    Participants who discontinued treatment before Cycle 12 Day 28 (cycle length= 28 days).

  6. Overall Survival (OS)

    Time frame: Up to approximately 48 months

    OS is defined as the time from the first study treatment to death from any cause.

  7. Progression-free Survival (PFS) as Determined by the Investigator According to iwCLL Guidelines

    Time frame: Up to approximately 48 months

    PFS is defined as the time from the first study treatment to the first occurrence of disease progression (PD) or death from any cause during study, whichever occurs first, as determined by the investigator according to the iwCLL.

  8. Event-free Survival (EFS) as Determined by the Investigator According to iwCLL Guidelines

    Time frame: Up to approximately 48 months

    EFS is defined as the time from the first study treatment to the first occurrence of PD, anti-leukemic treatment subsequent to the study treatment, or death from any cause during study, whichever occurs first, as determined by the investigator according to the iwCLL.

  9. Duration of Response (DOR) in Participants With CR/CRi or PR as Determined by the Investigator According to iwCLL Guidelines

    Time frame: Up to approximately 12 months

    DOR is defined as the time from the first occurrence of a documented objective response (i.e., CR/CRi or PR) to PD or death from any cause, whichever occurs first, as determined by the investigator according to the iwCLL.

  10. DOR in Participants With CR or CRi as Determined by the Investigator According to iwCLL Guidelines

    Time frame: Up to approximately 12 months

    DOR is defined as the time from the first occurrence of a documented objective response (i.e., CR or CRi ) to PD or death from any cause, whichever occurs first, as determined by the investigator according to the iwCLL.

  11. Time to Next CLL Treatment (TTNT)

    Time frame: Up to approximately 12 months

    TTNT is defined as the time from the first study treatment to the start of anti-leukemic treatment subsequent to the study treatment or death, whichever occurs first.

Sponsors and collaborators

Lead sponsor

Genentech, Inc.

Industry

Registry information

Official study title

Phase II, Open-label, Prospective Single-arm, Multi-center Clinical Trial to Evaluate if Adding Venetoclax to Patients on Covalent BTKi For 1L CLL Can Achieve Deep Durable Remissions (by UMRD 10^-4) to Allow Off-treatment Period

Acronym: BRAVE

Important dates

Study start
2024
Primary completion
2026
Study completion
2030
First posted
Jul 29, 2024
Registry last updated
Feb 25, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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