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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
19/07/2024

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:
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
Washington
Country [5] 0 0
United States of America
State/province [5] 0 0
Wisconsin
Country [6] 0 0
Argentina
State/province [6] 0 0
Buenos Aires
Country [7] 0 0
Argentina
State/province [7] 0 0
Caba
Country [8] 0 0
Argentina
State/province [8] 0 0
Santa Fe
Country [9] 0 0
Belgium
State/province [9] 0 0
Vlaams-Brabant
Country [10] 0 0
Brazil
State/province [10] 0 0
Sao Paulo
Country [11] 0 0
Canada
State/province [11] 0 0
New Brunswick
Country [12] 0 0
Canada
State/province [12] 0 0
Quebec
Country [13] 0 0
Chile
State/province [13] 0 0
Biobio
Country [14] 0 0
Chile
State/province [14] 0 0
Coquimbo
Country [15] 0 0
Chile
State/province [15] 0 0
Region M. De Santiago
Country [16] 0 0
Colombia
State/province [16] 0 0
Valle Del Cauca
Country [17] 0 0
France
State/province [17] 0 0
Nord
Country [18] 0 0
France
State/province [18] 0 0
Puy-de-Dome
Country [19] 0 0
France
State/province [19] 0 0
Vendee
Country [20] 0 0
Germany
State/province [20] 0 0
Rheinland-Pfalz
Country [21] 0 0
Germany
State/province [21] 0 0
Sachsen
Country [22] 0 0
Israel
State/province [22] 0 0
Haifa
Country [23] 0 0
Israel
State/province [23] 0 0
Jerusalem
Country [24] 0 0
Israel
State/province [24] 0 0
Ramat Gan
Country [25] 0 0
Israel
State/province [25] 0 0
Tel Aviv
Country [26] 0 0
Italy
State/province [26] 0 0
Alessandria
Country [27] 0 0
Italy
State/province [27] 0 0
Milano
Country [28] 0 0
Italy
State/province [28] 0 0
Reggio Emilia
Country [29] 0 0
Puerto Rico
State/province [29] 0 0
San Juan
Country [30] 0 0
South Africa
State/province [30] 0 0
Gauteng
Country [31] 0 0
South Africa
State/province [31] 0 0
Western Cape
Country [32] 0 0
Spain
State/province [32] 0 0
Barcelona
Country [33] 0 0
Spain
State/province [33] 0 0
Madrid
Country [34] 0 0
Spain
State/province [34] 0 0
Valenciana, Comunitat
Country [35] 0 0
United Kingdom
State/province [35] 0 0
England
Country [36] 0 0
United Kingdom
State/province [36] 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
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT05947851