A Study of Nemtabrutinib vs Chemoimmunotherapy for Participants With Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Without TP53 Aberrations (MK-1026-008, BELLWAVE-008)
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| ClinicalTrials.gov Identifier: NCT05624554 |
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Recruitment Status :
Recruiting
First Posted : November 22, 2022
Last Update Posted : June 2, 2023
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Sponsor:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC
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Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of nemtabrutinib compared to investigator's choice of fludarabine plus cyclophosphamide plus rituximab (FCR) or bendamustine plus rituximab (BR) in participants with previously untreated CLL/SLL without 17p deletion and/or tumor protein (TP) 53 mutation. The primary hypothesis is that nemtabrutinib is superior to FCR/BR with respect to progression-free survival (PFS).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Chronic Lymphocytic Leukemia Small Lymphocytic Leukemia | Drug: Nemtabrutinib Drug: Fludarabine Drug: Cyclophosphamide Drug: Bendamustine Biological: Rituximab Biological: Truxima Biological: Ruxience Biological: Riabni | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 300 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Single (Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3, Randomized Study to Compare the Efficacy and Safety of Nemtabrutinib Versus Chemoimmunotherapy for Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Without TP53 Aberrations |
| Actual Study Start Date : | March 16, 2023 |
| Estimated Primary Completion Date : | May 7, 2027 |
| Estimated Study Completion Date : | February 7, 2031 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Nemtabrutinib
Administered daily via oral tablet.
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Drug: Nemtabrutinib
65 mg administered orally daily until disease progression, unacceptable toxicity, or discontinuation criteria met
Other Name: MK-1026 |
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Active Comparator: FCR or BR
Investigator's choice of fludarabine plus cyclophosphamide plus rituximab (FCR) OR bendamustine plus rituximab (BR). Participants will receive either rituximab or specified approved rituximab biosimilar.
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Drug: Fludarabine
25 mg/m^2 administered via intravenous (IV) infusion on Days 1, 2, and 3 of each 28-day cycle up to 6 cycles Drug: Cyclophosphamide 250 mg/m^2 administered via IV infusion on Days 1, 2, and 3 of each 28-day cycle up to 6 cycles Drug: Bendamustine Administered via IV infusion on Days 1 and 2 of each 28-day cycle up to 6 cycles. The first dose is given as 70 to 90 mg/m^2. Subsequent doses may be escalated up to 90 mg/m^2, if applicable and as per local guidelines Biological: Rituximab Administered as an IV infusion on Day 1 of each 28-day cycle. The initial dose is 375 mg/m^2 (cycle 1) followed by 500 mg/m^2 for remaining cycles
Other Name: RITUXAN® Biological: Truxima Administered as an IV infusion on Day 1 of each 28-day cycle. The initial dose is 375 mg/m^2 (cycle 1) followed by 500 mg/m^2 for remaining cycles
Other Name: Rituximab biosimilar Biological: Ruxience Administered as an IV infusion on Day 1 of each 28-day cycle. The initial dose is 375 mg/m^2 (cycle 1) followed by 500 mg/m^2 for remaining cycles
Other Name: Rituximab biosimilar Biological: Riabni Administered as an IV infusion on Day 1 of each 28-day cycle. The initial dose is 375 mg/m^2 (cycle 1) followed by 500 mg/m^2 for remaining cycles
Other Name: Rituximab biosimilar |
Primary Outcome Measures :
- Progression-Free Survival (PFS) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 49 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 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria 2018 as assessed by blinded independent central review (BICR).
Secondary Outcome Measures :
- Overall Survival (OS) [ Time Frame: Up to approximately 94 months ]OS is defined as the time from randomization to death due to any cause.
- Objective Response Rate (ORR) per iwCLL Criteria 2018 as Assessed by BICR [ Time Frame: Up to approximately 36 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.
- Duration of Response (DOR) per iwCLL Criteria 2018 as Assessed by BICR [ Time Frame: Up to approximately 94 months ]For participants who demonstrate a CR, CRi, nPR, or PR per iwCLL criteria 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.
- Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 94 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
- Number of Participants Who Discontinue Study Treatment Due to an AE [ Time Frame: Up to approximately 94 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
The main inclusion and exclusion criteria include but are not limited to the following:
Inclusion Criteria:
- Confirmed diagnosis of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) and active disease clearly documented to have a need to initiate therapy
- Has previously untreated CLL/SLL participants without tumor protein 53 (TP53) aberrations and documented 11q status and immunoglobulin heavy chain gene (IGHV) mutational status
- The ability to swallow and retain oral medication
Exclusion Criteria:
- Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
- Gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
- Known additional malignancy that is progressing or has required active treatment within the past 3 years, except basal cell carcinoma of skin, squamous cell carcinoma of skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potential curative therapy
- History of severe bleeding disorders
- Not adequately recovered from major surgery or has ongoing surgical complications
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05624554
Contacts
| Contact: Toll Free Number | 1-888-577-8839 | Trialsites@merck.com |
Locations
Show 27 study locations
Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
| Study Director: | Medical Director | Merck Sharp & Dohme LLC |
Additional Information:
| Responsible Party: | Merck Sharp & Dohme LLC |
| ClinicalTrials.gov Identifier: | NCT05624554 |
| Other Study ID Numbers: |
1026-008 2022-500164-35-00 ( Registry Identifier: EU CT ) MK-1026-008 ( Other Identifier: Merck ) 2021-006593-23 ( EudraCT Number ) |
| First Posted: | November 22, 2022 Key Record Dates |
| Last Update Posted: | June 2, 2023 |
| Last Verified: | May 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf |
| URL: | http://engagezone.msd.com/ds_documentation.php |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Leukemia Leukemia, Lymphoid Leukemia, Lymphocytic, Chronic, B-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Leukemia, B-Cell Chronic Disease Disease Attributes Pathologic Processes Cyclophosphamide |
Bendamustine Hydrochloride Rituximab Fludarabine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antineoplastic Agents, Immunological |