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).
Recruiting
Phase 3Interventional Study
Leukemia, Lymphocytic, Chronic, B-CellLeukemia, Chronic LymphocyticSmall-Cell LymphomaLymphoma, Small LymphocyticCLLSLL
No Placebo Group
Every participant receives an active treatment — no one gets a placebo.
Pivotal Trial
This treatment is in the last trial phase before FDA approval.
Prior Safety Data
This treatment has already been tested in at least one earlier human trial.
Ready to participate?
Review the details below, then apply to join this clinical trial.
At a Glance
Age
18 and older
Sex
Any
Trial phase
Phase 3
Study type
Interventional
Purpose
Treatment
Participants needed
735 (estimated)
Sponsor
Merck Sharp & Dohme LLC · Industry
Who this trial is looking for
This trial is looking for people with chronic lymphocytic leukemia (CLL) whose disease has returned after treatment. Participants will receive a combination of two medications to see if this treatment is safer and more effective than another standard treatment.
Are You a Good Fit for This Trial?
Rules you outRichter TransformationCentral nervous system involvementHIV with specific recent health issues
You may be able to join if
I have been diagnosed with chronic lymphocytic leukemia.
I have had at least one previous treatment.
I have disease markers.
I can swallow and keep down oral medications.
I have a life expectancy of at least 3 months.
I have an Eastern Cooperative Oncology Group performance status of 0 to 2.
I'm not pregnant or breastfeeding, or I use effective contraception.
You may not be able to join if
I have an active hepatitis B or C infection.
I have a serious heart condition.
I have had another type of cancer that required treatment in the last 2 years.
I have had an active infection needing systemic therapy recently.
I have received prior systemic anticancer therapy within the last month.
I have had major surgery and haven't fully recovered.
I have severe bleeding disorders.
I have a known allergy to some of these medications.
Summarized in plain language from this trial's official eligibility criteria.
The full criteria are further down this page — only the research team can
confirm whether you qualify.
Think this trial could be right for you?
Answer three quick questions written from this study's own rules to see if you may qualify. No account needed to find out.
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) cr…
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).
Trial Locations
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Status
Eligibility Criteria
Inclusion 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, and immunoglobulin heavy chain gene (IGHV) mutation status…
Inclusion 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, and immunoglobulin heavy chain gene (IGHV) 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
Exclusion Criteria:
* 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 2 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
* Clinically significant cardiovascular disease
* 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) within ≤ 12 months before randomization or has received prior radiotherapy within 2 weeks of start of study intervention, or radiation related toxicities, requiring corticosteroids
* 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
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