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)

• ClinicalTrials.gov Identifier: NCT05624554
• Recruitment Status: Recruiting
• First Posted: November 22, 2022
• Last Update Posted: May 17, 2024
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: November 14, 2022
• First Posted Date: November 22, 2022
• Last Update Posted Date: May 17, 2024
• Actual Study Start Date: March 16, 2023
• Estimated Primary Completion Date: May 19, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 3, 2023)

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).

Original Primary Outcome Measures (submitted: November 14, 2022)

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 50 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).

Current Secondary Outcome Measures (submitted: November 14, 2022)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief 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)
• 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
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment

Condition

• Chronic Lymphocytic Leukemia
• Small Lymphocytic Leukemia

Intervention

• Drug: Nemtabrutinib
  65 mg administered orally daily until disease progression, unacceptable toxicity, or discontinuation criteria met
  Other Name: MK-1026
• 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

Study Arms

• Experimental: Nemtabrutinib
  Administered daily via oral tablet.
  Intervention: Drug: Nemtabrutinib
• 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.
  Interventions:

  • Drug: Fludarabine
  • Drug: Cyclophosphamide
  • Drug: Bendamustine
  • Biological: Rituximab
  • Biological: Truxima
  • Biological: Ruxience
  • Biological: Riabni

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 14, 2022): 300
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 17, 2031
• Estimated Primary Completion Date: May 19, 2027 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Australia, Brazil, Chile, China, Colombia, Denmark, Guatemala, Hong Kong, Hungary, Malaysia, Mexico, Poland, Romania, Singapore, South Africa, Taiwan, Turkey, Ukraine, United States

Administrative Information

• NCT Number: 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 )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: May 2024