Clinical trial 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.
Official 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2024-07-29
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Undetected Minimal Residual Disease at 10^-4 (uMRD4) PB Rates at EOCT
timeFrame: Cycle 12 Day 28 (Cycle length= 28 Days)
Secondary outcomes:
measure: CR/CRi Rate at EOCT as Determined by the Investigator According to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Guidelines
timeFrame: Up to approximately 12 months
measure: Partial Response (PR) Rate at EOCT as Determined by the Investigator According to iwCLL Guidelines
timeFrame: Up to approximately 12 months
measure: Overall Response Rate (ORR) at EOCT as Determined by the Investigator According to iwCLL Guidelines
timeFrame: Up to approximately 12 months
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to approximately 24 months
measure: Number of Participants Who Withdrew Prematurely from the Study
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers (Aurora) - USOR
state: Colorado
city: Athens
country: United States
facility: University Cancer & Blood Center, LLC
state: Georgia
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Inc
state: Indiana
city: Des Moines
country: United States
facility: Mission Blood and Cancer - MercyOne Cancer Center
state: Iowa
city: Bethesda
country: United States
facility: American Oncology Partners of Maryland, PA
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute - Hematologic Oncology Treatment Center
state: Massachusetts
city: Grand Island
country: United States
facility: Nebraska Cancer Specialists St Francis - Grand Island
state: Nebraska
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: East Brunswick
country: United States
facility: Astera Cancer Care East Brunswick
state: New Jersey
city: Farmington
country: United States
facility: San Juan Oncology Associates, PC
state: New Mexico
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc - Cincinnati - USOR
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Medford
country: United States
facility: Asante Rogue Regional Medical Center
state: Oregon
city: Springfield
country: United States
facility: Oncology Associates of Oregon, P.C.
state: Oregon
city: Chattanooga
country: United States
facility: Tennessee Oncology, PLLC - Chattanooga
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology - Midtown
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology- Northeast Texas
state: Texas
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: