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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

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 diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication.
* Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed.
* 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)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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California
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United States of America
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Indiana
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United States of America
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Iowa
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United States of America
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Michigan
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United States of America
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New Jersey
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United States of America
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Pennsylvania
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United States of America
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Washington
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United States of America
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Wisconsin
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Brazil
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Sao Paulo
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Brazil
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Rio de Janeiro
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Canada
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Ontario
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Canada
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Quebec
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Chile
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Region M. De Santiago
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China
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Anhui
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China
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Beijing
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China
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Chongqing
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China
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Guangdong
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China
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Guangxi
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China
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Guizhou
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China
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Hainan
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China
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Hubei
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China
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Hunan
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China
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Jiangsu
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China
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Jiangxi
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China
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Jilin
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China
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Shaanxi
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China
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Shandong
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China
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Shanxi
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China
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Tianjin
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China
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Xinjiang
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Colombia
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Cesar
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Colombia
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Cordoba
Country [34] 0 0
Colombia
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Valle Del Cauca
Country [35] 0 0
Czechia
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Olomouc
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Germany
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Berlin
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Hong Kong
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Hong Kong
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Petah Tikva
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Israel
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Ramat Gan
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Israel
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Zerifin
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Japan
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Aichi
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Japan
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Gunma
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Japan
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Hokkaido
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Japan
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Hyogo
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Japan
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Miyagi
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Japan
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Osaka
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Japan
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Shimane
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Japan
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Tokyo
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Japan
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Chiba
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Japan
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Fukuoka
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Japan
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Hiroshima
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Japan
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Okayama
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Japan
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Yamagata
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Malaysia
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Pulau Pinang
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New Zealand
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Waikato
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New Zealand
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Auckland
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Norway
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Oslo
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Peru
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Ariqipa
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Peru
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Lima
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Portugal
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Porto
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South Africa
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Gauteng
Country [64] 0 0
South Africa
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Western Cape
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Spain
State/province [65] 0 0
Barcelona
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Spain
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Cataluna
Country [67] 0 0
Spain
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Madrid, Comunidad De
Country [68] 0 0
Spain
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Madrid
Country [69] 0 0
Spain
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Santa Cruz De Tenerife
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Spain
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Salamanca
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Taiwan
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Kaohsiung
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Taiwan
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Tainan
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Taiwan
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Taipei
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Taiwan
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Taoyuan
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Thailand
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Chiang Mai
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Thailand
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Krung Thep Maha Nakhon
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Thailand
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Phitsanulok
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Thailand
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Songkhla
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United Kingdom
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Bristol, City Of
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United Kingdom
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London, City Of
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United Kingdom
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Oxfordshire
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United Kingdom
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Suffolk
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United Kingdom
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Windsor And Maidenhead
Country [84] 0 0
United Kingdom
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Barnet
Country [85] 0 0
United Kingdom
State/province [85] 0 0
Leeds

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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


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/NCT06136559