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. (BRAVE)

Genentech

Status and phase: Enrolling; Phase 2

Conditions: Chronic Lymphocytic Leukemia

Treatments: Drug: cBTKi Monotherapy; Drug: Venetoclax

Study type: Interventional

Funder types: Industry

Identifiers

NCT06524375

ML45219

Details and patient eligibility

About

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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. Progressive or stable disease on cBTKi
3. Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (Richter's transformation or pro-lymphocytic leukemia)
4. History of cardiomyopathy
5. Hypersensitivity to venetoclax or to any of the excipients (e.g., trehalose)
6. Clinically significant cardiovascular disease
7. Active bleeding or history of bleeding diathesis
8. Pregnant women and nursing mothers
9. Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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100 participants in 1 patient group

Venetoclax Added to cBTKi (Commercially Prescribed)

Experimental group

Description:

Participants will receive venetoclax, orally, once daily (QD) as ramp-up dosing at a starting dose of 20 milligrams (mg) on Day 1 of Cycle 1 (cycle length= 28 days) with weekly dose increases until the target dose of 400 mg is reached. Thereafter, participants will continue receiving venetoclax at 400 mg, orally, 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 previoulsy prescribed by the investigator in accordance with its prescribing label for up to 12 months.

Treatment:

Drug: Venetoclax

Drug: cBTKi Monotherapy