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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05947851




Registration number
NCT05947851
Ethics application status
Date submitted
7/07/2023
Date registered
17/07/2023
Date last updated
26/11/2024

Titles & IDs
Public title
A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010)
Scientific title
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)
Secondary ID [1] 0 0
MK-1026-010
Secondary ID [2] 0 0
1026-010
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Leukemia, Lymphocytic, Chronic, B-Cell 0 0
Leukemia, Chronic Lymphocytic 0 0
Small-Cell Lymphoma 0 0
Lymphoma, Small Lymphocytic 0 0
CLL 0 0
SLL 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nemtabrutinib
Treatment: Drugs - Venetoclax
Treatment: Other - Rituximab

Experimental: Nemtabrutinib + Venetoclax - Participants will receive nemtrabrutinib oral tablets at specified doses daily starting at Cycle 1 Day 1 (C1D1) and venetoclax oral tablets at doses of 20 mg up to 400 mg daily starting at Cycle 2 Day 1 (C2D1) up to 2 years post C2D1 or until progressive disease (PD) or discontinuation. A cycle = 4 weeks.

Active comparator: Venetoclax + Rituximab - Participants will receive venetoclax oral tablets at doses from 20 mg up to 400 mg daily starting at C1D1 on 4-week cycles up to 2 years and rituximab or biosimilar at 375 mg/m\^2 up to 500 mg/m2 intravenous infusion once per 28-day cycle starting at C2D1, for 6 total cycles. Treatment will continue until progressive disease (PD) or discontinuation.


Treatment: Drugs: Nemtabrutinib
5 and 20 mg tablets

Treatment: Drugs: Venetoclax
10, 50, and 100 mg tablets

Treatment: Other: Rituximab
100 mg/10 mL, 500 mg/50 mL (10 mg/mL) IV Infusion
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Number of participants experiencing dose-limiting toxicities (DLTs)
Timepoint [1] 0 0
Up to approximately 12 Weeks
Primary outcome [2] 0 0
Part 1: Number of participants experiencing adverse events (AEs)
Timepoint [2] 0 0
Up to approximately 28 months
Primary outcome [3] 0 0
Part 1: Number of participants discontinuing study treatment due to AEs
Timepoint [3] 0 0
Up to approximately 25 months
Primary outcome [4] 0 0
Part 2: PFS per the 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria as assessed by Blinded Independent Central Review (BICR)
Timepoint [4] 0 0
Up to approximately 71 months
Secondary outcome [1] 0 0
Part 2: Undetectable minimal residual disease (MRD) rate in bone marrow as assessed by central laboratory
Timepoint [1] 0 0
Month 14
Secondary outcome [2] 0 0
Part 2: Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 108 months
Secondary outcome [3] 0 0
Part 2: Objective Response Rate (ORR) per iwCLL Criteria 2018 as assessed by BICR
Timepoint [3] 0 0
Up to approximately 108 months
Secondary outcome [4] 0 0
Part 2: Duration of Response (DOR) per iwCLL Criteria 2018 as assessed by BICR
Timepoint [4] 0 0
Up to approximately 108 months
Secondary outcome [5] 0 0
Part 2: Number of participants experiencing AEs
Timepoint [5] 0 0
Up to approximately 28 months
Secondary outcome [6] 0 0
Part 2: Number of participants discontinuing study treatment due to AEs
Timepoint [6] 0 0
Up to approximately 25 months

Eligibility
Key inclusion criteria
* Confirmed diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and active disease clearly documented to initiate therapy.
* Deletion (Del) (17p) status, tumor protein 53 (TP53) mutation status, immunoglobulin heavy chain gene (IGHV) mutation status and Bruton's tyrosine kinase (BTK)-C481 mutation status results required before randomization for Part 2 participants only.
* Relapsed or refractory to at least 1 prior available therapy.
* Have at least 1 marker of disease burden.
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days before randomization.
* Has a life expectancy of at least 3 months.
* Has the ability to swallow and retain oral medication.
* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV deoxyribonucleic acid (DNA) viral load before randomization.
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV ribonucleic acid (RNA) viral load is undetectable at screening.
* Participants with human immunodeficiency virus (HIV) who meet ALL eligibility criteria.
* Participants with adequate organ function with specimens collected within 7 days before the start of study intervention.
* If capable of producing sperm, participant agrees to eliminate Nemtabrutinib: 12 days, Venetoclax: 1 month (30 days), Rituximab (rituximab biosimilar): not applicable; abstains from penile-vaginal intercourse as their preferred and usual lifestyle; OR uses prescribed contraception.
* Participant assigned female sex at birth are eligible to participate if not pregnant or breastfeeding and are not a person of childbearing potential (POCBP) OR is a POCBP and uses a contraceptive method that is highly effective, has a negative highly sensitive pregnancy test, and abstains from breastfeeding.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has an active hepatitis B virus/ hepatitis C virus (HBV/HCV) infection.
* Has gastrointestinal (GI) dysfunction that may affect drug absorption.
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Has diagnosis of Richter Transformation or active central nervous system (CNS) involvement by CLL/SLL.
* Has an active infection requiring systemic therapy, such as intravenous (IV) antibiotics, during screening.
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease and/or acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in the past 12 months before screening.
* Has QT interval corrected (QTc) prolongation or other significant electrocardiogram (ECG) abnormalities.
* Has a known allergy/sensitivity to nemtabrutinib or contraindication to venetoclax/rituximab (or rituximab biosimilar), or any of the excipients.
* Has history of severe bleeding disorders (eg, hemophilia).
* Has received prior systemic anticancer therapy within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibody) before randomization.
* Has received prior B-cell lymphoma 2 inhibitor(s) (BCL2i) including venetoclax or Non-covalent Bruton's tyrosine kinase inhibitor (BTKi).
* Is currently being treated with p-glycoprotein (P-gp) substrates with a narrow therapeutic index, cytochrome P450 3A (CYP3A) strong or moderate inducers or CYP3A strong inhibitors.
* Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention.
* Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration.
* Has a known psychiatric or substance use disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
* Participants who have not adequately recovered from major surgery or have ongoing surgical complications.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/08/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
27/06/2033
Actual
Sample size
Target
720
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Royal Adelaide Hospital ( Site 1104) - Adelaide
Recruitment hospital [2] 0 0
Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 1103) - Melbourne
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3021 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Oregon
Country [5] 0 0
United States of America
State/province [5] 0 0
Washington
Country [6] 0 0
United States of America
State/province [6] 0 0
Wisconsin
Country [7] 0 0
Argentina
State/province [7] 0 0
Buenos Aires
Country [8] 0 0
Argentina
State/province [8] 0 0
Caba
Country [9] 0 0
Argentina
State/province [9] 0 0
Santa Fe
Country [10] 0 0
Belgium
State/province [10] 0 0
Vlaams-Brabant
Country [11] 0 0
Brazil
State/province [11] 0 0
Sao Paulo
Country [12] 0 0
Canada
State/province [12] 0 0
New Brunswick
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
Chile
State/province [14] 0 0
Biobio
Country [15] 0 0
Chile
State/province [15] 0 0
Coquimbo
Country [16] 0 0
Chile
State/province [16] 0 0
Region M. De Santiago
Country [17] 0 0
Colombia
State/province [17] 0 0
Valle Del Cauca
Country [18] 0 0
France
State/province [18] 0 0
Nord
Country [19] 0 0
France
State/province [19] 0 0
Puy-de-Dome
Country [20] 0 0
France
State/province [20] 0 0
Vendee
Country [21] 0 0
Germany
State/province [21] 0 0
Rheinland-Pfalz
Country [22] 0 0
Germany
State/province [22] 0 0
Sachsen
Country [23] 0 0
Israel
State/province [23] 0 0
Haifa
Country [24] 0 0
Israel
State/province [24] 0 0
Jerusalem
Country [25] 0 0
Israel
State/province [25] 0 0
Ramat Gan
Country [26] 0 0
Israel
State/province [26] 0 0
Tel Aviv
Country [27] 0 0
Italy
State/province [27] 0 0
Alessandria
Country [28] 0 0
Italy
State/province [28] 0 0
Milano
Country [29] 0 0
Italy
State/province [29] 0 0
Reggio Emilia
Country [30] 0 0
Puerto Rico
State/province [30] 0 0
San Juan
Country [31] 0 0
South Africa
State/province [31] 0 0
Gauteng
Country [32] 0 0
South Africa
State/province [32] 0 0
Western Cape
Country [33] 0 0
Spain
State/province [33] 0 0
Barcelona
Country [34] 0 0
Spain
State/province [34] 0 0
Madrid
Country [35] 0 0
Spain
State/province [35] 0 0
Valenciana, Comunitat
Country [36] 0 0
Turkey
State/province [36] 0 0
Tekirdas
Country [37] 0 0
Turkey
State/province [37] 0 0
Ankara
Country [38] 0 0
United Kingdom
State/province [38] 0 0
England
Country [39] 0 0
United Kingdom
State/province [39] 0 0
London, City Of

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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).
Trial website
https://clinicaltrials.gov/study/NCT05947851
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05947851