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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06136559




Registration number
NCT06136559
Ethics application status
Date submitted
13/11/2023
Date registered
18/11/2023
Date last updated
7/11/2024

Titles & IDs
Public title
A Study of Nemtabrutinib (MK-1026) Versus Comparator (Investigator's Choice of Ibrutinib or Acalabrutinib) in First Line (1L) Chronic Lymphocytic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL) (MK-1026-011/BELLWAVE-011)
Scientific title
A Phase 3, Randomized Study to Compare Nemtabrutinib Versus Comparator (Investigator's Choice of Ibrutinib or Acalabrutinib) in Participants With Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BELLWAVE-011)
Secondary ID [1] 0 0
2022-501697-19
Secondary ID [2] 0 0
1026-011
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukemia 0 0
Small Lymphocytic Lymphoma 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 - Ibrutinib
Treatment: Drugs - Acalabrutinib

Experimental: Nemtabrutinib - Participants will receive nemtabrutinib at specified dose until disease progression, unacceptable toxicity or until discontinuation criteria are met.

Active comparator: Ibrutinib/Acalabrutinib - Participants will receive investigator's choice of ibrutinib or acalabrutinib at specified dose until disease progression, unacceptable toxicity or until discontinuation criteria are met.


Treatment: Drugs: Nemtabrutinib
Administered orally

Treatment: Drugs: Ibrutinib
Administered orally

Treatment: Drugs: Acalabrutinib
Administered orally
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) per Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 as assessed by Blinded Independent Central Review (BICR)
Timepoint [1] 0 0
Up to ~33 months
Primary outcome [2] 0 0
Progression-Free Survival (PFS) per iwCLL Criteria 2018 as assessed by BICR
Timepoint [2] 0 0
Up to ~104 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Up to ~104 months
Secondary outcome [2] 0 0
Duration of Response (DOR) per iwCLL Criteria 2018 as assessed by BICR
Timepoint [2] 0 0
Up to ~104 months
Secondary outcome [3] 0 0
Number of Participants Who Experience One or More Adverse Events (AEs)
Timepoint [3] 0 0
Up to ~104 months
Secondary outcome [4] 0 0
Number of Participants Who Discontinue Study Treatment Due to an AE
Timepoint [4] 0 0
Up to ~104 months

Eligibility
Key inclusion criteria
The main inclusion criteria include but are not limited to the following:

* Confirmed diagnosis of CLL/SLL and active disease clearly documented to have a need to initiate therapy.
* Has 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 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
The main exclusion criteria include but are not limited to the following:

* Has an active hepatitis B virus/ hepatitis C virus (HBV/HCV) infection.
* Has gastrointestinal (GI) dysfunction that may affect drug absorption.
* Has diagnosis of Richter Transformation or active central nervous system (CNS) involvement by CLL/SLL.
* Has had acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in the past 12 months before screening.
* Has clinically significant cardiovascular disease.
* Has hypersensitivity to nemtabrutinib or contraindication to ibrutinib or acalabrutinib, or any of the excipients.
* Has history of severe bleeding disorder.
* Has history of second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
* Has received any systemic anticancer therapy for CLL/SLL.
* 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.
* Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids.
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
* Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration.
* Has active infection requiring systemic therapy.
* 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
Open (masking not used)
Who is / are masked / blinded?



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
13/12/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2032
Actual
Sample size
Target
1200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Royal North Shore Hospital ( Site 2806) - St Leonards
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment outside Australia
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United States of America
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Alabama
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California
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Wisconsin
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Guangxi
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Ramat Gan
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Edirne
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Windsor And Maidenhead
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Barnet
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United Kingdom
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Leeds

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

Ethics approval
Ethics application status

Summary
Brief summary
The goal of this study is to evaluate nemtabrutinib compared with investigator's choice of ibrutinib or acalabrutinib in participants with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who have not received any prior therapy. The primary hypotheses are that (1) nemtabrutinib is non-inferior to ibrutinib or acalabrutinib with respect to objective response rate (ORR) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 by blinded independent central review (BICR) and (2) nemtabrutinib is superior to ibrutinib or acalabrutinib with respect to progression free survival (PFS) per iwCLL Criteria 2018 by BICR.
Trial website
https://clinicaltrials.gov/study/NCT06136559
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/NCT06136559