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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05624554




Registration number
NCT05624554
Ethics application status
Date submitted
14/11/2022
Date registered
22/11/2022
Date last updated
19/07/2024

Titles & IDs
Public title
A Study of Nemtabrutinib vs Chemoimmunotherapy for Participants With Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Without TP53 Aberrations (MK-1026-008, BELLWAVE-008)
Scientific title
A Phase 3, Randomized Study to Compare the Efficacy and Safety of Nemtabrutinib Versus Chemoimmunotherapy for Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Without TP53 Aberrations
Secondary ID [1] 0 0
2022-500164-35-00
Secondary ID [2] 0 0
1026-008
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
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 - Fludarabine
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Bendamustine
Treatment: Other - Rituximab
Treatment: Other - Truxima
Treatment: Other - Ruxience
Treatment: Other - Riabni

Experimental: Nemtabrutinib - Administered daily via oral tablet.

Active comparator: FCR or BR - Investigator's choice of fludarabine plus cyclophosphamide plus rituximab (FCR) OR bendamustine plus rituximab (BR). Participants will receive either rituximab or specified approved rituximab biosimilar.


Treatment: Drugs: Nemtabrutinib
65 mg administered orally daily until disease progression, unacceptable toxicity, or discontinuation criteria met

Treatment: Drugs: Fludarabine
25 mg/m\^2 administered via intravenous (IV) infusion on Days 1, 2, and 3 of each 28-day cycle up to 6 cycles

Treatment: Drugs: Cyclophosphamide
250 mg/m\^2 administered via IV infusion on Days 1, 2, and 3 of each 28-day cycle up to 6 cycles

Treatment: Drugs: Bendamustine
Administered via IV infusion on Days 1 and 2 of each 28-day cycle up to 6 cycles. The first dose is given as 70 to 90 mg/m\^2. Subsequent doses may be escalated up to 90 mg/m\^2, if applicable and as per local guidelines

Treatment: Other: Rituximab
Administered as an IV infusion on Day 1 of each 28-day cycle. The initial dose is 375 mg/m\^2 (cycle 1) followed by 500 mg/m\^2 for remaining cycles

Treatment: Other: Truxima
Administered as an IV infusion on Day 1 of each 28-day cycle. The initial dose is 375 mg/m\^2 (cycle 1) followed by 500 mg/m\^2 for remaining cycles

Treatment: Other: Ruxience
Administered as an IV infusion on Day 1 of each 28-day cycle. The initial dose is 375 mg/m\^2 (cycle 1) followed by 500 mg/m\^2 for remaining cycles

Treatment: Other: Riabni
Administered as an IV infusion on Day 1 of each 28-day cycle. The initial dose is 375 mg/m\^2 (cycle 1) followed by 500 mg/m\^2 for remaining cycles
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
Progression-Free Survival (PFS) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 as Assessed by Blinded Independent Central Review (BICR)
Timepoint [1] 0 0
Up to approximately 49 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Up to approximately 94 months
Secondary outcome [2] 0 0
Objective Response Rate (ORR) per iwCLL Criteria 2018 as Assessed by BICR
Timepoint [2] 0 0
Up to approximately 36 months
Secondary outcome [3] 0 0
Duration of Response (DOR) per iwCLL Criteria 2018 as Assessed by BICR
Timepoint [3] 0 0
Up to approximately 94 months
Secondary outcome [4] 0 0
Number of Participants Who Experience an Adverse Event (AE)
Timepoint [4] 0 0
Up to approximately 94 months
Secondary outcome [5] 0 0
Number of Participants Who Discontinue Study Treatment Due to an AE
Timepoint [5] 0 0
Up to approximately 94 months

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



* Confirmed diagnosis of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) and active disease clearly documented to have a need to initiate therapy
* Has previously untreated CLL/SLL participants without tumor protein 53 (TP53) aberrations and documented 11q status and immunoglobulin heavy chain gene (IGHV) mutational status
* The ability to swallow and retain oral medication
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
* Gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
* Known additional malignancy that is progressing or has required active treatment within the past 3 years, except basal cell carcinoma of skin, squamous cell carcinoma of skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potential curative therapy
* History of severe bleeding disorders
* Not adequately recovered from major surgery or has 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
16/03/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
17/03/2031
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Royal Adelaide Hospital ( Site 1105) - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
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
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Mississippi
Country [4] 0 0
United States of America
State/province [4] 0 0
Washington
Country [5] 0 0
Brazil
State/province [5] 0 0
Parana
Country [6] 0 0
Brazil
State/province [6] 0 0
Sao Paulo
Country [7] 0 0
Brazil
State/province [7] 0 0
Rio de Janeiro
Country [8] 0 0
Bulgaria
State/province [8] 0 0
Plovdiv
Country [9] 0 0
Bulgaria
State/province [9] 0 0
Vratsa
Country [10] 0 0
Chile
State/province [10] 0 0
Araucania
Country [11] 0 0
Chile
State/province [11] 0 0
Biobio
Country [12] 0 0
Chile
State/province [12] 0 0
Coquimbo
Country [13] 0 0
Chile
State/province [13] 0 0
Region M. De Santiago
Country [14] 0 0
China
State/province [14] 0 0
Beijing
Country [15] 0 0
China
State/province [15] 0 0
Chongqing
Country [16] 0 0
China
State/province [16] 0 0
Guangdong
Country [17] 0 0
China
State/province [17] 0 0
Guizhou
Country [18] 0 0
China
State/province [18] 0 0
Hainan
Country [19] 0 0
China
State/province [19] 0 0
Henan
Country [20] 0 0
China
State/province [20] 0 0
Hubei
Country [21] 0 0
China
State/province [21] 0 0
Hunan
Country [22] 0 0
China
State/province [22] 0 0
Jiangsu
Country [23] 0 0
China
State/province [23] 0 0
Jiangxi
Country [24] 0 0
China
State/province [24] 0 0
Jilin
Country [25] 0 0
China
State/province [25] 0 0
Shaanxi
Country [26] 0 0
China
State/province [26] 0 0
Shanghai
Country [27] 0 0
China
State/province [27] 0 0
Shanxi
Country [28] 0 0
China
State/province [28] 0 0
Tianjin
Country [29] 0 0
China
State/province [29] 0 0
Zhejiang
Country [30] 0 0
Colombia
State/province [30] 0 0
Antioquia
Country [31] 0 0
Colombia
State/province [31] 0 0
Cesar
Country [32] 0 0
Colombia
State/province [32] 0 0
Risaralda
Country [33] 0 0
Denmark
State/province [33] 0 0
Midtjylland
Country [34] 0 0
Denmark
State/province [34] 0 0
Nordjylland
Country [35] 0 0
Denmark
State/province [35] 0 0
Syddanmark
Country [36] 0 0
Guatemala
State/province [36] 0 0
Guatemala
Country [37] 0 0
Hong Kong
State/province [37] 0 0
Hksar
Country [38] 0 0
Hungary
State/province [38] 0 0
Fejer
Country [39] 0 0
Hungary
State/province [39] 0 0
Heves
Country [40] 0 0
Hungary
State/province [40] 0 0
Szabolcs-Szatmar-Bereg
Country [41] 0 0
Malaysia
State/province [41] 0 0
Johor
Country [42] 0 0
Malaysia
State/province [42] 0 0
Selangor
Country [43] 0 0
Mexico
State/province [43] 0 0
Distrito Federal
Country [44] 0 0
Mexico
State/province [44] 0 0
Michoacan
Country [45] 0 0
Mexico
State/province [45] 0 0
Oaxaca
Country [46] 0 0
Poland
State/province [46] 0 0
Lubelskie
Country [47] 0 0
Poland
State/province [47] 0 0
Mazowieckie
Country [48] 0 0
Poland
State/province [48] 0 0
Pomorskie
Country [49] 0 0
Poland
State/province [49] 0 0
Slaskie
Country [50] 0 0
Poland
State/province [50] 0 0
Swietokrzyskie
Country [51] 0 0
Poland
State/province [51] 0 0
Warminsko-mazurskie
Country [52] 0 0
Romania
State/province [52] 0 0
Bucuresti
Country [53] 0 0
Romania
State/province [53] 0 0
Cluj
Country [54] 0 0
Singapore
State/province [54] 0 0
Central Singapore
Country [55] 0 0
South Africa
State/province [55] 0 0
Gauteng
Country [56] 0 0
South Africa
State/province [56] 0 0
Western Cape
Country [57] 0 0
Taiwan
State/province [57] 0 0
Kaohsiung
Country [58] 0 0
Taiwan
State/province [58] 0 0
Tainan
Country [59] 0 0
Taiwan
State/province [59] 0 0
Taipei
Country [60] 0 0
Turkey
State/province [60] 0 0
Istanbul
Country [61] 0 0
Turkey
State/province [61] 0 0
Tekirdas
Country [62] 0 0
Turkey
State/province [62] 0 0
Ankara
Country [63] 0 0
Turkey
State/province [63] 0 0
Izmir
Country [64] 0 0
Ukraine
State/province [64] 0 0
Cherkaska Oblast
Country [65] 0 0
Ukraine
State/province [65] 0 0
Ivano-Frankivska Oblast
Country [66] 0 0
Ukraine
State/province [66] 0 0
Kyivska Oblast
Country [67] 0 0
Ukraine
State/province [67] 0 0
Lvivska Oblast
Country [68] 0 0
Ukraine
State/province [68] 0 0
Kyiv

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/NCT05624554