Chronic Lymphocytic Leukemia Clinical Trial
Official 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)
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.
| Status | Recruiting |
| Enrollment | 1200 |
| Est. completion date | September 30, 2032 |
| Est. primary completion date | September 30, 2032 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 history of second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 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 diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication. - Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed. - Has active infection requiring systemic therapy. - Participants who have not adequately recovered from major surgery or have ongoing surgical complications. |
| Country | Name | City | State |
|---|---|---|---|
| Brazil | Hospital Paulistano-Americas Oncologia ( Site 2202) | Sao Paulo | |
| Brazil | Hospital 9 De Julho ( Site 2206) | São Paulo | Sao Paulo |
| Canada | The Ottawa Hospital - General Campus ( Site 0102) | Ottawa | Ontario |
| Canada | Centre intégré de santé et de services sociaux du Bas Saint-Laurent- Hôpital régional de Rimouski ( | Rimouski | Quebec |
| Chile | Bradfordhill-Clinical Area ( Site 2310) | Santiago | Region M. De Santiago |
| Chile | Clínica Alemana de Santiago-Unidad de Investigaciones ( Site 2306) | Santiago | Region M. De Santiago |
| Chile | FALP-UIDO ( Site 2300) | Santiago | Region M. De Santiago |
| Israel | Rambam Health Care Campus-Hematology and Bone Marrow Transplantation ( Site 1503) | Haifa | |
| Israel | Hadassah Medical Center-Hemato-Oncology ( Site 1500) | Jerusalem | |
| Israel | Sheba Medical Center-Hemato Oncology ( Site 1501) | Ramat Gan | |
| Israel | Yitzhak Shamir Medical Center. ( Site 1506) | Zerifin | |
| Japan | Chiba cancer center ( Site 1905) | Chiba | |
| Japan | Shimane University Hospital ( Site 1911) | Izumo | Shimane |
| Japan | Kobe City Medical Center General Hospital ( Site 1910) | Kobe | Hyogo |
| Japan | Japanese Foundation for Cancer Research ( Site 1906) | Koto | Tokyo |
| Japan | Osaka Red Cross Hospital ( Site 1908) | Osaka | |
| Japan | Yamagata University Hospital ( Site 1902) | Yamagata | |
| Taiwan | National Cheng Kung University Hospital ( Site 1700) | Tainan | |
| Taiwan | Chang Gung Medical Foundation-Linkou Branch ( Site 1703) | Taoyuan | |
| United Kingdom | St Bartholomew's Hospital-Centre for Experimental Cancer Medicine ( Site 3006) | London | London, City Of |
| United Kingdom | GenesisCare - Cambridge ( Site 3001) | Newmarket | Suffolk |
| United Kingdom | The Churchill Hospital ( Site 3007) | Oxford | Oxfordshire |
| United Kingdom | GenesisCare - Windsor ( Site 3002) | Windsor | Windsor And Maidenhead |
| United States | Summit Medical Group Cancer Center ( Site 0007) | Florham Park | New Jersey |
| United States | University of Iowa-Holden Comprehensive Cancer Center ( Site 0017) | Iowa City | Iowa |
| United States | University Hospital and UW Health Clinics ( Site 0006) | Madison | Wisconsin |
| United States | Medical Oncology Associates, PS (dba Summit Cancer Centers) ( Site 0010) | Spokane | Washington |
| United States | Cancer Care Associates Of York ( Site 0005) | York | Pennsylvania |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC |
United States, Brazil, Canada, Chile, Israel, Japan, Taiwan, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Objective Response Rate (ORR) per Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 as assessed by Blinded Independent Central Review (BICR) | 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. | Up to ~33 months | |
| Primary | Progression-Free Survival (PFS) per iwCLL Criteria 2018 as assessed by BICR | 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. | Up to ~104 months | |
| Secondary | Overall Survival (OS) | OS is defined as the time from randomization to death due to any cause. | Up to ~104 months | |
| Secondary | Duration of Response (DOR) per iwCLL Criteria 2018 as assessed by BICR | 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. | Up to ~104 months | |
| Secondary | Number of Participants Who Experience One or More Adverse Events (AEs) | 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. | Up to ~104 months | |
| Secondary | Number of Participants Who Discontinue Study Treatment Due to an AE | 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. | Up to ~104 months |
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|---|---|---|---|
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