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NCT Number: NCT06136559

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)

The goal of this study is to evaluate nemtabrutinib compared with investigator's choice of ibrutinib or acalabrutinib in participants with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who have not received any prior therapy. The primary hypotheses are that (1) nemtabrutinib is non-inferior to ibrutinib or acalabrutinib with respect to objective response rate (ORR) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 by blinded independent central review (BICR) and (2) nemtabrutinib is superior to ibrutinib or acalabrutinib with respect to progression free survival (PFS) per iwCLL Criteria 2018 by BICR.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Royal North Shore Hospital ( Site 2806), St Leonards, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

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 known additional malignancy that is progressing or has required active treatment within the past 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 active infection requiring systemic therapy, including intravenous (IV) antibiotics during screening.
  • Participants who have not adequately recovered from major surgery or have ongoing surgical complications.

Treatment and study plan

Nemtabrutinib

Drug

Administered orally

Other names: MK-1026, ARQ 531

Ibrutinib

Drug

Administered orally

Acalabrutinib

Drug

Administered orally

Primary outcomes

  1. Objective Response Rate (ORR) per Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 as assessed by Blinded Independent Central Review (BICR)

    Time frame: Up to ~33 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.

  2. Progression-Free Survival (PFS) per iwCLL Criteria 2018 as assessed by BICR

    Time frame: Up to ~104 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 iwCLL Criteria 2018 as assessed by BICR.

Secondary outcomes

  1. Overall Survival (OS)

    Time frame: Up to ~104 months

    OS is defined as the time from randomization to death due to any cause.

  2. Duration of Response (DOR) per iwCLL Criteria 2018 as assessed by BICR

    Time frame: Up to ~104 months

    For participants who demonstrate a 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, 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.

  3. Number of Participants Who Experience One or More Adverse Events (AEs)

    Time frame: Up to ~104 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.

  4. Number of Participants Who Discontinue Study Treatment Due to an AE

    Time frame: Up to ~104 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Toll Free Number

CONTACT

[email protected]

1-888-577-8839

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study 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)

Important dates

Study start
2023
Primary completion
2032
Study completion
2032
First posted
Nov 18, 2023
Registry last updated
Jul 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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