Chronic Lymphocytic Leukemia
Conditions
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.
Interventions
DRUGVenetoclax
Venetoclax tablets will be administered as per the schedule specified in the arm.
DRUGcBTKi Monotherapy
Commercially available cBTKi (ibrutinib or acalabrutinib, or zanubrutinib) will be administered in accordance with its prescribing label.
Sponsors
Genentech, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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 2. Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to (\</=) 2 3. Adequate renal and liver function
Exclusion criteria
1. Prior B-cell lymphoma (Bcl-2) inhibitor therapy 2. Anti-cluster of differentiation 20 (CD20) therapy within the month prior to screening 3. Progressive or stable disease on cBTKi 4. Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (Richter's transformation or pro-lymphocytic leukemia) 5. History of cardiomyopathy 6. Hypersensitivity to venetoclax or to any of the excipients (e.g., trehalose) 7. Clinically significant cardiovascular disease 8. Active bleeding or history of bleeding diathesis 9. Pregnant women and nursing mothers 10. Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| uMRD4 Rate 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
| Measure | Time frame | Description |
|---|---|---|
| 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 at EOCT, as determined by the investigator according to the iwCLL. |
| 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 at EOCT, as determined by the investigator according to the iwCLL. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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. |
| Number of Participants Who Withdrew Prematurely from the Study | Up to approximately 12 months | Participants who discontinued treatment before Cycle 12 Day 28 (cycle length= 28 days). |
| Overall Survival (OS) | Up to approximately 48 months | OS is defined as the time from the first study treatment to death from any cause. |
| Progression-free Survival (PFS) as Determined by the Investigator According to iwCLL Guidelines | 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. |
| Event-free Survival (EFS) as Determined by the Investigator According to iwCLL Guidelines | 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. |
| Duration of Response (DOR) in Participants With CR/CRi or PR as Determined by the Investigator According to iwCLL Guidelines | 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. |
| DOR in Participants With CR or CRi as Determined by the Investigator According to iwCLL Guidelines | 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. |
| 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 at EOCT, as determined by the investigator according to the iwCLL. |
| Time to Next CLL Treatment (TTNT) | 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. |
Countries
United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed