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Trial record 1 of 1 for:    MK-1026-008
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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)

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ClinicalTrials.gov Identifier: NCT05624554
Recruitment Status : Recruiting
First Posted : November 22, 2022
Last Update Posted : May 10, 2024
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Description
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Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of nemtabrutinib compared to investigator's choice of fludarabine plus cyclophosphamide plus rituximab (FCR) or bendamustine plus rituximab (BR) in participants with previously untreated CLL/SLL without 17p deletion and/or tumor protein (TP) 53 mutation. The primary hypothesis is that nemtabrutinib is superior to FCR/BR with respect to progression-free survival (PFS).

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Leukemia Drug: Nemtabrutinib Drug: Fludarabine Drug: Cyclophosphamide Drug: Bendamustine Biological: Rituximab Biological: Truxima Biological: Ruxience Biological: Riabni Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : March 16, 2023
Estimated Primary Completion Date : May 19, 2027
Estimated Study Completion Date : March 17, 2031

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Nemtabrutinib
Administered daily via oral tablet.
 Drug: Nemtabrutinib
65 mg administered orally daily until disease progression, unacceptable toxicity, or discontinuation criteria met
Other Name: MK-1026
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.
 Drug: 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

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

Drug: 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

Biological: 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
Other Name: RITUXAN®

Biological: 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
Other Name: Rituximab biosimilar

Biological: 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
Other Name: Rituximab biosimilar

Biological: 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
Other Name: Rituximab biosimilar


Outcome Measures
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Primary Outcome Measures :
  1. Progression-Free Survival (PFS) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 49 months ]
    PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. PD is evaluated per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria 2018 as assessed by blinded independent central review (BICR).


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to approximately 94 months ]
    OS is defined as the time from randomization to death due to any cause.

  2. Objective Response Rate (ORR) per iwCLL Criteria 2018 as Assessed by BICR [ Time Frame: Up to approximately 36 months ]
    ORR is defined as the percentage of participants with complete response (CR), complete response with an incomplete recovery of the participant's bone marrow (CRi), nodular partial response (nPR), or Partial response (PR), per iwCLL criteria 2018 as assessed by BICR.

  3. Duration of Response (DOR) per iwCLL Criteria 2018 as Assessed by BICR [ Time Frame: Up to approximately 94 months ]
    For participants who demonstrate a CR, CRi, nPR, or PR per iwCLL criteria as assessed by BICR, DOR is defined as the time from the first documented evidence of CR, CRi, nPR, or PR that led to response until disease progression or death due to any cause, whichever occurs first.

  4. Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 94 months ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

  5. Number of Participants Who Discontinue Study Treatment Due to an AE [ Time Frame: Up to approximately 94 months ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Inclusion Criteria:

  • 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

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05624554


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
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Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
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Study Director: Medical Director Merck Sharp & Dohme LLC
More Information
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Additional Information:

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Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT05624554    
Other Study ID Numbers: 1026-008
2022-500164-35-00 ( Registry Identifier: EU CT )
MK-1026-008 ( Other Identifier: Merck )
2021-006593-23 ( EudraCT Number )
First Posted: November 22, 2022    Key Record Dates
Last Update Posted: May 10, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hematologic Diseases
Leukemia, B-Cell
Chronic Disease
Disease Attributes
Pathologic Processes
 Cyclophosphamide
Bendamustine Hydrochloride
Rituximab
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological