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)

Sponsor

Merck Sharp & Dohme LLC (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05624554

Collaborator

(none)

300

Enrollment

Arms

95.2

Anticipated Duration (Months)

Study Details

Study Description

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 Design

Study Type:

Interventional

Anticipated 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

Anticipated Study Start Date :

Jan 17, 2023

Anticipated Primary Completion Date :

Feb 20, 2027

Anticipated Study Completion Date :

Dec 23, 2030

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nemtabrutinib Administered daily via oral tablet.	Drug: Nemtabrutinib 65 mg administered orally daily until disease progression, unacceptable toxicity, or discontinuation criteria met Other Names: MK-1026
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.	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 Names: 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 Names: 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 Names: 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 Names: Rituximab biosimilar

Arm

Intervention/Treatment

Experimental: Nemtabrutinib

Administered daily via oral tablet.

Drug: Nemtabrutinib

65 mg administered orally daily until disease progression, unacceptable toxicity, or discontinuation criteria met

Other Names:

MK-1026

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.

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 Names:

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 Names:

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 Names:

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 Names:

Rituximab biosimilar

Outcome Measures

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) [Up to approximately 50 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) [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 [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 [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) [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 [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

Confirmed diagnosis of CLL/SLL and active disease clearly documented to have a need to initiate therapy.
Has previously untreated CLL/SLL without TP53 aberrations. Prior palliative radiation therapy administered locally is permitted.
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.