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).
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)
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
Not stated in the study description — ask the study team about visits and procedures.
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study is for people with CLL/SLL, types of blood cancer, that came back or did not respond to at least one treatment. It checks the safety and dose of nemtabrutinib with venetoclax. It also tests whether this pair keeps cancer from getting worse longer than venetoclax with rituximab.
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).
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Have confirmed CLL/SLL that needs treatment and at least one sign of how much cancer is present.
- Have cancer that came back or did not respond to at least one past treatment.
- For Part 2, have results for three cancer gene tests: del(17p), TP53, and IGHV.
- Be able to care for yourself and be out of bed for at least half the day, with an expected life span of at least 3 months.
- Have organs that work well enough and be able to swallow and keep down pills.
- Some people with hepatitis B or past hepatitis C may join if virus levels cannot be detected. Hepatitis B also requires at least 4 weeks of antiviral treatment. People with HIV must meet all study rules.
- If able to produce sperm, follow the study's rules for birth control or not having penis-in-vagina sex.
- If assigned female at birth, do not be pregnant or breastfeeding. If able to become pregnant, use highly effective birth control and have a negative pregnancy test.
Who can't join
- Have active hepatitis B or C, or an active infection needing treatment throughout the body. Certain HIV-related illnesses or infections also prevent joining.
- Have gut problems that could affect how the body takes in the medicines.
- Have another cancer that is getting worse or needed treatment in the past 2 years; CLL/SLL that has changed into a faster-growing cancer; or CLL/SLL in the brain or spinal cord.
- Have serious heart or blood vessel disease, a history of severe bleeding problems, or an allergy or other medical reason not to take the study drugs.
- Have had cancer treatment too recently, including a BCL2-blocking drug within 12 months or radiation within 2 weeks. Radiation side effects needing steroids also prevent joining.
- Take certain medicines that interact with the study drugs, have had a live vaccine within 30 days, or have used an experimental drug or device within 4 weeks.
- Have a mental health or substance use disorder that would make it hard to follow study rules.
- Have not healed well enough from major surgery or still have problems from surgery.
Simplified for readability. The official criteria below are what the study team uses.
Official 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 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
Study sites (25)
AR
- Highlands Oncology Group ( Site 5405) · Springdale, AR 72762Study Coordinator · Study contact · 479-872-8130More trials in Springdale
CA
- MemorialCare Health System - Long Beach Medical Center ( Site 5421) · Long Beach, CA 90806Study Coordinator · Study contact · 562-933-7866More trials in Long Beach
FL
- Clermont Oncology Center ( Site 5430) · Clermont, FL 34711Study Coordinator · Study contact · 386-538-3169More trials in Clermont
- Memorial Hospital West ( Site 5410) · Pembroke Pines, FL 33028Study Coordinator · Study contact · 954-844-8318More trials in Pembroke Pines
IN
- Fort Wayne Medical Oncology and Hematology ( Site 5444) · Fort Wayne, IN 46804Study Coordinator · Study contact · 260-436-0800More trials in Fort Wayne
MD
- Center for Cancer and Blood Disorders ( Site 5439) · Bethesda, MD 20817Study Coordinator · Study contact · 301-571-2016More trials in Bethesda
MN
- Avera Cancer Institute - Marshall ( Site 5462) · Marshall, MN 56258Study Coordinator · Study contact · 605-601-1830More trials in Marshall
MO
- MidAmerica Cancer Care, LLC ( Site 5426) · Kansas City, MO 64132Study Coordinator · Study contact · 816-974-5050More trials in Kansas City
MS
- Hattiesburg Clinic Hematology/Oncology ( Site 5416) · Hattiesburg, MS 39401Study Coordinator · Study contact · 601-261-1700More trials in Hattiesburg
MT
- Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana ( Site 5433) · Billings, MT 59102Study Coordinator · Study contact · 406-238-6685More trials in Billings
NJ
- Atlantic Health System Morristown Medical Center ( Site 5445) · Morristown, NJ 07960Study Coordinator · Study contact · 973-971-5000More trials in Morristown
NV
- Renown Regional Medical Center-Renown Health Medical Oncology ( Site 5434) · Reno, NV 89502Study Coordinator · Study contact · 775-982-4000More trials in Reno
NY
- New York Oncology Hematology, P.C. ( Site 5453) · Albany, NY 12208Study Coordinator · Study contact · 518-262-6696More trials in Albany
OR
- Oregon Health and Science University ( Site 5425) · Portland, OR 97239-3011Study Coordinator · Study contact · 503-494-5058More trials in Portland
SD
- Avera Cancer Institute - Aberdeen ( Site 5458) · Aberdeen, SD 57401Study Coordinator · Study contact · 605-601-1830More trials in Aberdeen
- Avera Cancer Institute - Mitchell ( Site 5461) · Mitchell, SD 57301Study Coordinator · Study contact · 605-322-3299More trials in Mitchell
- Avera Cancer Institute - Pierre ( Site 5460) · Pierre, SD 57501Study Coordinator · Study contact · 605-601-1830More trials in Pierre
- Avera Cancer Institute- Research ( Site 5437) · Sioux Falls, SD 57105Study Coordinator · Study contact · 605-322-3035More trials in Sioux Falls
- Avera Cancer Institute - Yankton ( Site 5459) · Yankton, SD 57078Study Coordinator · Study contact · 605-601-1830More trials in Yankton
TX
- PatientCare Clinical Research LLC ( Site 5435) · Sugar Land, TX 77479Study Coordinator · Study contact · 929-712-7467More trials in Sugar Land
VA
- University of Virginia Cancer Center ( Site 5402) · Charlottesville, VA 22903Study Coordinator · Study contact · 434-924-9333More trials in Charlottesville
WA
- Vista Oncology ( Site 5449) · Olympia, WA 98506Study Coordinator · Study contact · 360-413-8880More trials in Olympia
- Medical Oncology Associates, PS ( Site 5406) · Spokane, WA 99208Study Coordinator · Study contact · 509-462-2273More trials in Spokane
WI
- University of Wisconsin Hospital and Clinics-Carbone Cancer Center ( Site 5423) · Madison, WI 53792More trials in Madison
WV
- West Virginia University ( Site 5447) · Morgantown, WV 26506Study Coordinator · Study contact · 304-598-4500More trials in Morgantown