The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
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
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.