A Phase 3, Open-label, Randomized Study to Compare the Efficacy and Safety of Nemtabrutinib (MK-1026) Plus Venetoclax Versus Venetoclax Plus Rituximab in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Following at Least 1 Prior Therapy (BELLWAVE-010)
Summary
The purpose of this study is to assess the safety and tolerability and to confirm the dose of nemtabrutinib in combination with venetoclax in participants with R/R CLL/SLL. The primary study hypotheses are that the combination of nemtabrutinib plus venetoclax is superior to VR with respect to progression-free survival (PFS) per 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria as assessed by blinded independent central review (BICR).
Arms & interventions
- DrugNemtabrutinib
5, 20, 45, and 65 mg tablets
- DrugVenetoclax
10, 50, and 100 mg tablets
- BiologicalRituximab
100 mg/10 mL, 500 mg/50 mL (10 mg/mL) IV Infusion
Outcome measures
Primary
Part 1: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
DLT evaluation period is defined as 8 weeks after the first dose of the combination treatment of nemtabrutinib plus venetoclax Cycle 2 Day 1 in Part 1 + 4 weeks follow up. Each cycle is 4 weeks. DLTs are: Grade ≥3 nonhematologic toxicity (except Grade 3 nausea, vomiting, diarrhea, rash, fatigue, and uncontrolled hypertension which will not be considered a DLT unless lasting ≥72 hours despite optimal supportive care); Grade 4 hematologic toxicity lasting \>7 days (except Grade 3 lymphocytosis, Grade 4 platelet count decreased of any duration, or Grade 3 platelet count decreased if associated with bleeding); any Grade 3 or Grade 4 nonhematologic laboratory abnormality if values result in drug-induced liver injury, or medical intervention is required, or the abnormality leads to hospitalization, or the abnormality persists for \>1 week (with exceptions); missing \>25% of nemtabrutinib or venetoclax doses as a result of drug-related adverse events during the first 2 cycles; Grade 5 toxicity.
Time frame: Up to approximately 12 Weeks
Part 1: Number of Participants Experiencing Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants experiencing AEs will be reported for Part 1.
Time frame: Up to approximately 28 months
Part 1: Number of Participants Discontinuing Study Treatment Due to AEs
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants discontinuing study treatment due to AEs will be reported for Part 1.
Time frame: Up to approximately 25 months
Part 2: PFS per the 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria as Assessed by Blinded Independent Central Review (BICR)
PFS is defined as the time from randomization to the first documented disease progression per iwCLL criteria 2018 as accessed by BICR, or death due to any cause, whichever occurs first. PFS will be presented.
Time frame: Up to approximately 71 months
Secondary
Part 2: Undetectable Minimal Residual Disease (MRD) Rate in Bone Marrow as Assessed by Central Laboratory
Time frame: Up to approximately 46 months
Part 2: Overall Survival (OS)
Time frame: Up to approximately 108 months
Part 2: Objective Response Rate (ORR) per iwCLL Criteria 2018 as Assessed by BICR
Time frame: Up to approximately 71 months
Part 2: Duration of Response (DOR) per iwCLL Criteria 2018 as Assessed by BICR
Time frame: Up to approximately 108 months
Part 2: Number of Participants Experiencing AEs
Time frame: Up to approximately 28 months
Part 2: Number of Participants Discontinuing Study Treatment Due to AEs
Time frame: Up to approximately 25 months
Eligibility criteria
Study locations (6)
Highlands Oncology Group ( Site 5405)
Springdale, Arkansas, 72762
MemorialCare Health System - Long Beach Medical Center ( Site 5421)
Long Beach, California, 90806
Memorial Hospital West ( Site 5410)
Pembroke Pines, Florida, 33028
Oregon Health and Science University ( Site 5425)
Portland, Oregon, 97239-3011
Medical Oncology Associates, PS ( Site 5406)
Spokane, Washington, 99208
University of Wisconsin Hospital and Clinics-Carbone Cancer Center ( Site 5423)
Madison, Wisconsin, 53792