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.
- Conditions
- Chronic Lymphocytic Leukemia
- Interventions
- Drug: cBTKi Monotherapy
- Registration Number
- NCT06524375
- Lead Sponsor
- Genentech, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Venetoclax Added to cBTKi (Commercially Prescribed) Venetoclax 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 Day 1 of Cycle 2 up to Day 28 of Cycle 12. Participants will continue receiving cBTKi-monotherapy (i.e. ibrutinib or acalabrutinib, or zanubrutinib) as previously prescribed by the investigator according to the prescribing label. Venetoclax Added to cBTKi (Commercially Prescribed) cBTKi Monotherapy 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 Day 1 of Cycle 2 up to Day 28 of Cycle 12. Participants will continue receiving cBTKi-monotherapy (i.e. ibrutinib or acalabrutinib, or zanubrutinib) as previously prescribed by the investigator according to the prescribing label.
- Primary Outcome Measures
Name Time Method Undetected Minimal Residual Disease at 10^-4 (uMRD4) PB Rates at EOCT Cycle 12 Day 28 (Cycle length= 28 Days) uMRD4 will be assessed using next generation sequencing (NGS) (sensitivity 10\^-4) from PB.
- Secondary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Up to approximately 24 months Adverse events including adverse events of special interest (AESIs) 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.
Number of Participants Who Withdrew Prematurely from the Study Up to approximately 24 months Overall Response Rate (ORR) at EOCT as Determined by the Investigator According to iwCLL Guidelines Up to approximately 12 months ORR is defined as the percentage of participants with a CR/CRi or PR, as determined by the investigator according to the iwCLL.
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 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, as determined by the investigator according to the iwCLL.
Partial Response (PR) Rate at EOCT as Determined by the Investigator According to iwCLL Guidelines Up to approximately 12 months PR rate is defined as the percentage of participants with a PR, as determined by the investigator according to the iwCLL.
Trial Locations
- Locations (19)
Dana-Farber Cancer Institute - Hematologic Oncology Treatment Center
🇺🇸Boston, Massachusetts, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Highlands Oncology Group
🇺🇸Springdale, Arkansas, United States
Rocky Mountain Cancer Centers (Aurora) - USOR
🇺🇸Aurora, Colorado, United States
University Cancer & Blood Center, LLC
🇺🇸Athens, Georgia, United States
Fort Wayne Medical Oncology and Hematology, Inc
🇺🇸Fort Wayne, Indiana, United States
Mission Blood and Cancer - MercyOne Cancer Center
🇺🇸Des Moines, Iowa, United States
American Oncology Partners of Maryland, PA
🇺🇸Bethesda, Maryland, United States
Nebraska Cancer Specialists St Francis - Grand Island
🇺🇸Grand Island, Nebraska, United States
Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
Astera Cancer Care East Brunswick
🇺🇸East Brunswick, New Jersey, United States
San Juan Oncology Associates, PC
🇺🇸Farmington, New Mexico, United States
Oncology Hematology Care Inc - Cincinnati - USOR
🇺🇸Cincinnati, Ohio, United States
Asante Rogue Regional Medical Center
🇺🇸Medford, Oregon, United States
Oncology Associates of Oregon, P.C.
🇺🇸Springfield, Oregon, United States
Tennessee Oncology, PLLC - Chattanooga
🇺🇸Chattanooga, Tennessee, United States
Tennessee Oncology - Midtown
🇺🇸Nashville, Tennessee, United States
Texas Oncology- Northeast Texas
🇺🇸Tyler, Texas, United States