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
NCT Number: NCT06524375
Acronym: BRAVE
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Interventions: DRUG: Venetoclax|DRUG: cBTKi Monotherapy
Sponsor: Genentech, Inc.
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 100
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-09
Completion Date: 2028-02-08
Locations: Nebraska Cancer Specialists St Francis - Grand Island, Grand Island, Nebraska, 68803, United States|Nebraska Cancer Specialists, Fort Worth, Texas, 76177, United States

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.

Primary Outcome Measures: Undetected Minimal Residual Disease at 10^-4 (uMRD4) PB Rates 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 Outcome Measures: Overall Response Rate (ORR) as Determined by the Investigator According to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Guidelines, ORR is defined as the percentage of participants with a complete response (CR) /complete response with incomplete recovery of the bone marrow (CRi) or partial response (PR), as determined by the investigator according to the iwCLL, Up to approximately 12 months|CR/CRi Rate as Determined by the Investigator According to iwCLL Guidelines, CR/CRi rate is defined as the percentage of participants with a CR or CRi, as determined by the investigator according to the iwCLL., Up to approximately 12 months|PR Rate as Determined by the Investigator According to iwCLL Guidelines, PR rate is defined as the percentage of participants with a PR, as determined by the investigator according to the iwCLL., Up to approximately 12 months|Progression-Free Survival (PFS), PFS is defined as the time from the first study treatment to the first occurrence of disease progression or death from any cause during study, whichever occurs first, as determined by the investigator according to the iwCLL., Up to approximately 24 months|Event Free Survival (EFS), EFS is defined as the time from the first study treatment to the first occurrence of disease progression, 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., Up to approximately 24 months|Overall Survival (OS), OS defined as the time from the first study treatment to death from any cause. For participants who have not died at the time of analysis, OS will be censored on the last known alive date, Up to approximately 24 months|Duration of Response (DOR), DOR is defined as the time from the first occurrence of a documented objective response (i.e., CR/CRi or PR) to disease progression or death from any cause, whichever occurs first, as determined by the investigator according to the iwCLL, Up to approximately 24 months|DOR with CR or CRi, DOR in participants with best response of CR or CRi, defined for participants with best response of CR or CRi as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, as determined by the investigator according to the iwCLL., Up to approximately 24 months|Time to Next CLL Treatment (TTNT), TTNT defined as the time from the first study treatment to the start of antileukemic treatment subsequent to the study treatment or death, whichever occurs first., Up to approximately 24 months|Number of Participants With Adverse Events (AEs), Adverse events including adverse events of special interest (AESIs) and serious adverse events will be collected as part of this study at baseline and every clinical visit, until 30 days after the final dose of study treatment., Up to approximately 24 months