Nemtabrutinib and Venetoclax for the Treatment of Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

NCT07557056 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: OSU-25191NCI-2026-02422
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests how well nemtabrutinib and venetoclax work in treating patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Nemtabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cells (a type of white blood cell) in cancers such as CLL or SLL at abnormal levels. This may help keep cancer cells from growing and spreading. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Giving nemtabrutinib in combination with venetoclax may kill more cancer cells in patients with CLL or SLL.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• Presence of undetectable minimal residual disease (MRD)

  As measured by Adaptive ClonoSeq next generation sequencing at a level of 10\^-6 in the peripheral blood after 14 cycles of treatment with nemtabrutinib and venetoclax. The rate of undetectable MRD will be calculated in all eligible patients who start any amount of study drug, and the 95% confidence interval will be provided with the estimated rate.

  After 14 cycles of treatment (cycle length = 28 days)

Secondary Outcomes (7)

• Incidence of adverse events

  Up to 1 year

• Progression free survival (PFS)

  From date of treatment start to progression or death, whichever occurs first, assessed up to 1 year

• Time to next treatment

  From study treatment start to the date the next treatment starts, assessed up to 1 year

• Response to treatment

  Up to 1 year

• Presence of complete remission

  Up to 1 year

Study Arms (1)

Treatment (nemtabrutinib and venetoclax)

EXPERIMENTAL

Patients receive nemtabrutinib PO daily on days 1-28 of each cycle. Starting in cycle 3, patients also receive venetoclax PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 14 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT, bone marrow aspiration and biopsy, and blood sample collection throughout the trial.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Nemtabrutinib; Other: Questionnaire Administration; Drug: Venetoclax

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (nemtabrutinib and venetoclax)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration and biopsy

Treatment (nemtabrutinib and venetoclax)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow aspiration and biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (nemtabrutinib and venetoclax)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (nemtabrutinib and venetoclax)

Nemtabrutinib DRUG

Given PO

Also known as: ARQ 531, ARQ-531, ARQ531, Bruton's Tyrosine Kinase Inhibitor ARQ 531, BTK Inhibitor ARQ 531, MK-1026

Treatment (nemtabrutinib and venetoclax)

Questionnaire Administration OTHER

Ancillary studies

Treatment (nemtabrutinib and venetoclax)

Venetoclax DRUG

Given PO

Also known as: ABT 199, ABT-0199, ABT-199, ABT199, GDC 0199, GDC-0199, GDC0199, RG7601, Venclexta, Venclyxto

Treatment (nemtabrutinib and venetoclax)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of CLL/SLL meeting criteria established in the 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines
• Is an individual of any sex/gender, who is at least 18 years of age on the day of signing informed consent
• Participants must have treatment-naïve CLL/SLL. Palliative loco-regional radiotherapy, rituximab for autoimmune conditions, or corticosteroids for symptom control will not be considered prior therapy
• Participants must meet criteria for treatment as defined by 2018 iwCLL guidelines which includes at least one of the following criteria:
• Massive (\>= 6 cm below the costal margin), progressive or symptomatic splenomegaly
• Massive nodes (\>= 10 cm) or progressive or symptomatic lymphadenopathy
• Progressive lymphocytosis with a lymphocyte doubling time \< 6 months or an increase of \>= 50% over a 2 month period
• Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy
• Symptomatic or functional extranodal involvement (e.g. skin, kidney, lung, spine)
• Constitutional symptoms, which include any of the following:
• Unintentional weight loss of 10% or more within 6 months
• Significant fatigue
• Fevers \> 100.5 degrees Fahrenheit (F) for 2 weeks or more without evidence of infection
• Night sweats \>= 1 month without evidence of infection
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention

You may not qualify if:

• Subject with other malignancies that are associated with a life expectancy of \< 2 years or that would confound assessment of toxicity in this study.
• NOTE: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder
• Clinically significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification. Note: Subjects with controlled atrial fibrillation can enroll on study
• Active HBV/HCV infection
• Inability to swallow oral medication or gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy)
• Diagnosis of Richter transformation
• Active central nervous system (CNS) involvement
• Active infection requiring systemic therapy, including intravenous (IV) antibiotics during screening. Participants may be rescreened followed completion of IV antibiotic course
• AIDS defining opportunistic infection in the past 12 months prior to screening
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
• Corrected QT (QTc) prolongation (defined as a Fridericia-corrected QT interval \[QTcF\] \> 450 msecs) or other significant electrocardiogram (ECG) abnormalities including second degree atrioventricular (AV) block type II, third degree AV block, or bradycardia (ventricular rate less than 50 beats/min)
• Known allergy/sensitivity (\>= grade 3) to nemtabrutinib or any of the excipients.
• NOTE: Refer to the investigator brochure (IB) for details regarding excipients for nemtabrutinib
• History of severe bleeding disorders
• A POCBP who has a positive urine pregnancy test within 72 hours prior to enrollment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

Sponsors & Collaborators

• Jennifer Woyach: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Specimen Handling; Biopsy; ARQ531; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Jennifer A Woyach, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 22, 2026
• First Posted: April 29, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 29, 2026

Record last verified: 2026-04

Locations

US (1)