RECRUITING

A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010)

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Chronic Lymphocytic Small-Cell Lymphoma Lymphoma, Small Lymphocytic CLL SLL

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to assess the safety and tolerability and to confirm the dose of nemtabrutinib in combination with venetoclax in participants with R/R CLL/SLL. The primary study hypotheses are that the combination of nemtabrutinib plus venetoclax is superior to VR with respect to progression-free survival (PFS) per 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria as assessed by blinded independent central review (BICR).

Official Title

A Phase 3, Open-label, Randomized Study to Compare the Efficacy and Safety of Nemtabrutinib (MK-1026) Plus Venetoclax Versus Venetoclax Plus Rituximab in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Following at Least 1 Prior Therapy (BELLWAVE-010)

Quick Facts

Study Start:2023-08-08

Study Completion:2033-06-27

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05947851

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Confirmed diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and active disease clearly documented to initiate therapy. * Deletion (Del) (17p) status, tumor protein 53 (TP53) mutation status, immunoglobulin heavy chain gene (IGHV) mutation status and Bruton's tyrosine kinase (BTK)-C481 mutation status results required before randomization for Part 2 participants only. * Relapsed or refractory to at least 1 prior available therapy. * Have 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 a life expectancy of at least 3 months. * 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. * Participants with adequate organ function with specimens collected within 7 days before the start of study intervention. * If capable of producing sperm, participant agrees to eliminate Nemtabrutinib: 12 days, Venetoclax: 1 month (30 days), Rituximab (rituximab biosimilar): not applicable; abstains from penile-vaginal intercourse as their preferred and usual lifestyle; OR uses prescribed contraception. * Participant assigned female sex at birth are eligible to participate if not pregnant or breastfeeding and are not a person of childbearing potential (POCBP) OR is a POCBP and uses a contraceptive method that is highly effective, has a negative highly sensitive pregnancy test, and abstains from breastfeeding.	* Has an active hepatitis B virus/ hepatitis C virus (HBV/HCV) infection. * Has gastrointestinal (GI) dysfunction that may affect drug absorption. * Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. * Has diagnosis of Richter Transformation or active central nervous system (CNS) involvement by CLL/SLL. * Has an active infection requiring systemic therapy, such as intravenous (IV) antibiotics, during screening. * HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease and/or acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in the past 12 months before screening. * Has QT interval corrected (QTc) prolongation or other significant electrocardiogram (ECG) abnormalities. * Has a known allergy/sensitivity to nemtabrutinib or contraindication to venetoclax/rituximab (or rituximab biosimilar), or any of the excipients. * Has history of severe bleeding disorders (eg, hemophilia). * Has received prior systemic anticancer therapy within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibody) before randomization. * Has received prior B-cell lymphoma 2 inhibitor(s) (BCL2i) including venetoclax or Non-covalent Bruton's tyrosine kinase inhibitor (BTKi). * 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. * Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention. * Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration. * Has a known psychiatric or substance use disorder that would interfere with the participant's ability to cooperate with the requirements of the study. * Participants who have not adequately recovered from major surgery or have ongoing surgical complications.

Inclusion Criteria

Exclusion Criteria

* Confirmed diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and active disease clearly documented to initiate therapy.
* Deletion (Del) (17p) status, tumor protein 53 (TP53) mutation status, immunoglobulin heavy chain gene (IGHV) mutation status and Bruton's tyrosine kinase (BTK)-C481 mutation status results required before randomization for Part 2 participants only.
* Relapsed or refractory to at least 1 prior available therapy.
* Have 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 a life expectancy of at least 3 months.
* 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.
* Participants with adequate organ function with specimens collected within 7 days before the start of study intervention.
* If capable of producing sperm, participant agrees to eliminate Nemtabrutinib: 12 days, Venetoclax: 1 month (30 days), Rituximab (rituximab biosimilar): not applicable; abstains from penile-vaginal intercourse as their preferred and usual lifestyle; OR uses prescribed contraception.
* Participant assigned female sex at birth are eligible to participate if not pregnant or breastfeeding and are not a person of childbearing potential (POCBP) OR is a POCBP and uses a contraceptive method that is highly effective, has a negative highly sensitive pregnancy test, and abstains from breastfeeding.

* Has an active hepatitis B virus/ hepatitis C virus (HBV/HCV) infection.
* Has gastrointestinal (GI) dysfunction that may affect drug absorption.
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Has diagnosis of Richter Transformation or active central nervous system (CNS) involvement by CLL/SLL.
* Has an active infection requiring systemic therapy, such as intravenous (IV) antibiotics, during screening.
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease and/or acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in the past 12 months before screening.
* Has QT interval corrected (QTc) prolongation or other significant electrocardiogram (ECG) abnormalities.
* Has a known allergy/sensitivity to nemtabrutinib or contraindication to venetoclax/rituximab (or rituximab biosimilar), or any of the excipients.
* Has history of severe bleeding disorders (eg, hemophilia).
* Has received prior systemic anticancer therapy within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibody) before randomization.
* Has received prior B-cell lymphoma 2 inhibitor(s) (BCL2i) including venetoclax or Non-covalent Bruton's tyrosine kinase inhibitor (BTKi).
* 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.
* Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention.
* Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration.
* Has a known psychiatric or substance use disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
* Participants who have not adequately recovered from major surgery or have ongoing surgical complications.

Contacts and Locations

Study Contact

Toll Free Number

CONTACT

1-888-577-8839

Trialsites@msd.com

Principal Investigator

Medical Director

STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Study Locations (Sites)

Highlands Oncology Group ( Site 5405)

Springdale, Arkansas, 72762

United States

MemorialCare Health System - Long Beach Medical Center ( Site 5421)

Long Beach, California, 90806

United States

Memorial Hospital West ( Site 5410)

Pembroke Pines, Florida, 33028

United States

Oregon Health and Science University ( Site 5425)

Portland, Oregon, 97239-3011

United States

Medical Oncology Associates, PS ( Site 5406)

Spokane, Washington, 99208

United States

University of Wisconsin Hospital and Clinics-Carbone Cancer Center ( Site 5423)

Madison, Wisconsin, 53792

United States

Collaborators and Investigators

Sponsor: Merck Sharp & Dohme LLC

Medical Director, STUDY_DIRECTOR, Merck Sharp & Dohme LLC

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-08-08

Study Completion Date2033-06-27

Study Record Updates

Study Start Date2023-08-08

Study Completion Date2033-06-27

Terms related to this study

Additional Relevant MeSH Terms

Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Chronic Lymphocytic
Small-Cell Lymphoma
Lymphoma, Small Lymphocytic
CLL
SLL