Nemtabrutinib With Venetoclax and Obinutuzumab in Patients With Chronic Lymphocytic Leukemia

NCT07690891 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IIT-GURU-NEMTABRUTINIB-CLL
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open-label Phase 2 study designed to evaluate the treatment outcomes of nemtabrutinib-venetoclax-obinutuzumab as a frontline management for chronic lymphocytic leukemia (CLL).

Conditions

Chronic Lymphocytic Leukemia

Keywords

minimal residual disease

Outcome Measures

Primary Outcomes (1)

• Undetectable MRD

  This measure is the proportion of subjects with undetectable MRD at 10\^-4 sensitivity level by flow cytometry after treatment with nemtabrutinib, venetoclax, and obinutuzumab for frontline management of CLL.

  15 months

Study Arms (1)

Nemtabrutinib with Venetoclax and Obinutuzumab

EXPERIMENTAL

* Nemtabrutinib will be administered orally. * Venetoclax will be administered orally * Obinutuzumab will be administered intravenously.

Drug: Nemtabrutinib; Drug: Venetoclax; Drug: Obinutuzumab

Interventions

Nemtabrutinib DRUG

45 mg daily for 15 28-day cycles.

Also known as: MK-1026

Nemtabrutinib with Venetoclax and Obinutuzumab

Venetoclax DRUG

Cycle 4, Days 1-7: 20 mg; Cycle 4, Days 8-14: 50 mg; Cycle 4, Days 15-21: 100 mg; Cycle 4, Days 22-28: 200 mg; Cycle 5-15: 400 mg.

Also known as: Venclexta, Venclyxto

Nemtabrutinib with Venetoclax and Obinutuzumab

Obinutuzumab DRUG

Cycle 4, Day 1: 100 mg; Cycle 4, Day 2: 900 mg; Cycle 4, Day 8: 1000 mg; Cycle 4, Day 15: 1000 mg; Cycles 5-9, Day 1: 1000 mg.

Also known as: Gazyva

Nemtabrutinib with Venetoclax and Obinutuzumab

Eligibility Criteria

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

You may qualify if:

• Patients aged 18 years or older.
• Patients must have a diagnosis of CLL/ Small Lymphocytic Lymphoma (SLL)
• Patients must meet International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for treatment initiation.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Patient must meet the following screening clinical laboratory values as specified below:
• Hematologic: Absolute Neutrophil Count (ANC) of at least 1000 and platelet count of at least 50,000 unless these blood counts are low due to bone marrow involvement by CLL/SLL (use of growth factors, transfusions allowed to meet this criteria as clinically indicated).
• International normalized ratio (INR) OR prothrombin time (PT) ≤1.5 × Upper Limit of Normal (ULN) unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
• Hepatic:
• i. Total bilirubin ≤1.5 x upper limit of normal (ULN) OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN. Patients with Gilbert's syndrome can enroll if conjugated bilirubin is within normal limits and total bilirubin ≤3 x ULN).
• ii. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x ULN.
• Renal: Creatinine clearance of at least 30 mL/min based either on Cockroft-Gault estimate or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or urine collection (12 or 24 hour).
• Patient is able to swallow oral medications.
• Female subjects who:
• Are postmenopausal for at least one year before the screening visit, OR
• Are surgically sterile, OR

You may not qualify if:

• 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 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.
• Clinically significant cardiac issues (unless patient has a pacemaker) such as QTc prolongation (defined as a QTcF \>480 msecs) or other significant electrocardiogram (ECG) abnormalities including second degree AV block type II, third degree AV block, or bradycardia (ventricular rate less than 50 beats/min)
• Known allergy/sensitivity to nemtabrutinib or any of the excipients
• History of severe bleeding disorder defined as an ongoing congenital or acquired condition that leads to an increased likelihood of bleeding.
• History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years or no active therapy is needed.
• 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.
• \- A person of childbearing potential who has a positive urine pregnancy test within 72 hours prior to allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
• Prior/Concomitant Therapy
• Prior use of any BTKi or Bcl2 inhibitor

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasm, Residual

Interventions

venetoclax; obinutuzumab

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; Neoplastic Processes

Study Officials

• Guru S Guru Murthy, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Medical College of Wisconsin Cancer Center Clinical Trials Office

CONTACT

866-680-0505; cccto@mcw.edu

Study Design

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

Study Record Dates

• First Submitted: July 1, 2026
• First Posted: July 8, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): September 1, 2031
• Last Updated: July 8, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)