Mosunetuzumab for CLL MRD Clearance

NCT07052695 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 25-277
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this study is to test mosunetuzumab given alone or in combination with a Bruton tyrosine kinase inhibitor (BTKi, such as ibrutinib, acalabrutinib, zanubrutinib, or pirtobrutinib) in participants with CLL (chronic lymphocytic leukemia) or small lymphocytic lymphoma (SLL). The names of the study drugs in this research study are:

• Mosunetuzumab
• BTK inhibitor: Ibrutinib, acalabrutinib, zanubrutinib, or pirtobrutinib

Conditions

Leukemia; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Lymphoma

Keywords

Leukemia; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Lymphoma

Outcome Measures

Primary Outcomes (1)

• Rate of undetectable bone marrow minimal residual disease

  Undetectable bone marrow minimal residual disease (MRD) is defined by \< 1 CLL cell in 10,000 leukocytes (uMRD4) using an NGS-based assay at any time during C8 through C17 of mosunetuzumab.

  Up to 1 year

Secondary Outcomes (2)

• Safety of mosunetuzumab

  Up to 30 days after the last dose of mosunetuzumab.

• Efficacy of mosunetuzumab

  3 years from the initiation of study therapy

Study Arms (2)

BCL2i arm

EXPERIMENTAL

20 enrolled participants who have been previously treated with a BCL2i-containing regimen will receive up to 17 cycles of mosunetuzumab

Drug: Mosunetuzumab

BTKi arm

EXPERIMENTAL

20 enrolled participants who have been on a BTKi will receive up to 17 cycles of mosunetuzumab. Each participant will continue the BTKi during treatment with mosunetuzumab.

Drug: Mosunetuzumab; Drug: Ibrutinib; Drug: Acalabrutinib; Drug: Zanubrutinib; Drug: Pirtobrutinib

Interventions

Mosunetuzumab DRUG

Subcutaneous injection of a CD20xCD3 bispecific antibody

BCL2i arm; BTKi arm

Ibrutinib DRUG

For participants who have been ibrutinib PO prior to enrollment

BTKi arm

Acalabrutinib DRUG

For participants who have been acalabrutinib PO prior to enrollment

BTKi arm

Zanubrutinib DRUG

For participants who have been zanubrutinib PO prior to enrollment

BTKi arm

Pirtobrutinib DRUG

For participants who have been pirtobrutinib PO prior to enrollment

BTKi arm

Eligibility Criteria

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

You may qualify if:

• Meet 2018 iwCLL guidelines for the diagnosis of CLL or SLL
• Recent completion of treatment or ongoing treatment for CLL/SLL as follows:
• BTKi arm: On continuous BTKi therapy for \> 12 months, including \> 2 months at a stable dose.
• BTKis include ibrutinib, acalabrutinib, zanubrutinib and pirtobrutinib.
• The BTKi is the first- or second-line therapy for CLL.
• BCL2i arm: Completed BCL2i-based therapy \< 12 months of enrollment.
• BCL2i-based therapy must be the most recent CLL therapy prior to enrollment.
• BCL2i must have been given for at least 6 months for patients who were intolerant to a BCL2i and stopped the treatment without disease progression. For all others, at least 12 cycles of BCL2i therapy are required.
• BCL2i-based therapy should have been given as first- or second-line therapy for CLL.
• BCL2i-based regimens include venetoclax plus obinutuzumab (VO) or rituximab (VR), and the combination of a BTKi + a BCL2i +/- anti- CD20mAb.
• If BCL2i was continued after the combination, the subject is not eligible.
• Detectable minimal residual disease (MRD) of ≥10e-4 in peripheral blood (PB) or bone marrow (BM) based on an NGS-based assay.
• Age ≥ 18 years
• ECOG performance status ≤ 2
• Adequate organ and bone marrow function as defined by the study protocol.

You may not qualify if:

• Bulky disease with any lymph node \> 5cm or absolute lymphocyte count \> 100,000/microliter.
• Clinical progression of CLL at the time of enrollment.
• Prior treatment with chimeric antigen receptor T-cell therapy within 30 days of starting study therapy, or radioimmunotherapy within 12 weeks of starting study therapy.
• History of solid organ or allogeneic stem cell transplantation.
• Ongoing significant toxicity (Grade 3 or higher adverse events) from prior BCL2i- or BTKi- -based therapy at the time of enrollment.
• Known or suspected Richter's transformation or known CNS involvement of CLL.
• History of bleeding disorders (e.g. von Willebrand's disease, hemophilia).
• Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease.
• Significant cardiovascular disease such as uncontrolled arrhythmi, class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification, ejection fraction \< 40% by any methods in the 12 months of enrollment, unstable angina or acute coronary syndrome including myocardial infarction within 6 months of enrollment.
• Patients with significant pulmonary disease such as uncontrolled obstructive pulmonary disease, history of bronchospasm, uncontrolled idiopathic, autoimmune, or drug-induced interstitial lung disease, or uncontrolled drug induced or auto-immune pneumonitis
• Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis
• For patients with history of other malignancies with life expectancy of \< 2 years.
• Receiving any other investigational agents.
• Concurrent systemic immunosuppression (e.g. azathioprine, methotrexate, cyclosporine, tacrolimus, anti-TNF agents, anti-CD20 monoclonal antibody) within 30 days of starting study therapy or administration of \> 20 mg of prednisone or equivalent daily within 14 days of study therapy.
• Vaccinated with live vaccine within 4 weeks of starting study therapy.

Sponsors & Collaborators

• Inhye Ahn: lead
• Genentech, Inc.: collaborator

Study Sites (2)

Brigham & Women's Hospital

Boston, Massachusetts, 02215, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma

Interventions

ibrutinib; acalabrutinib; zanubrutinib; pirtobrutinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Inhye Ahn, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

DFCI Clinical Trials Hotline

CONTACT

877-DF-TRIAL; DFCILymphomaResearchNurses@partners.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: June 28, 2025
• First Posted: July 6, 2025
• Study Start: November 24, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2032
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)