NCT06357676

Glofitamab Plus Ibrutinib With Obinutuzumab for the Treatment of Patients With Mantle Cell Lymphoma, IGNITE MCL Trial

Integrated Glofit and Ibrutinib as Novel Immune Therapy Evaluation in Treatment-Naive Mantle Cell Lymphoma (IGNITE MCL): A Phase Ib/II Study of Glofitamab Plus Ibrutinib With Obinutuzumab Pretreatment in MCL Patients ≥ 65 or Ages 18-64 With High-Risk Features

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 27 (estimated)
• Sponsor: OHSU Knight Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase IB/II trial tests the safety, side effects and effectiveness of glofitamab plus ibrutinib with obinutuzumab for the treatment of patients with mantle cell lymphoma (MCL). Glofitamab is in a class of medications called bispecific monoclonal antibodies. It works by killing cancer cells. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). In the body, glofitamab binds to a receptor called CD3 on T-cells (a type of immune cells) and a receptor called CD20 on B-cells, a receptor that is often over-expressed on the surface of cancerous B-cells. When glofitamab binds to CD3 and CD20 receptors, it causes an immune response against the CD20-expressing cancerous B-cells. Ibrutinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop the spread of cancer cells. Obinutuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Glofitamab plus ibrutinib with obinutuzumab may be safe tolerable and/or effective in treating patients with MCL.

Detailed description

PRIMARY OBJECTIVES: I. Determine the safety and tolerability of treatment with glofitamab and ibrutinib (GLIB) for previously untreated MCL in patients with high risk or age ≥ 65 yrs. (Phase Ib) I. Determine the efficacy of treatment with GLIB for previously untreated MCL in patients with high risk disease or age ≥ 65 yrs. (Phase II) SECONDARY OBJECTIVES: I. Assess the overall acute toxicity and tolerability of treatment with GLIB. II. Assess the preliminary efficacy of treatment with GLIB based on clinical response. III. Assess survival in the absence of progressive disease, recurrence of disease, or death due to any cause after treatment with GLIB. IV. Assess the duration of clinical response and complete response to treatment with GLIB. EXPLORATORY OBJECTIVES: I. Evaluate response to treatment evaluated as minimal residual disease (MRD). II. Evaluate the differential impact of treatment on T cell populations in the tumor microenvironment. OUTLINE: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-21 of cycles 1-17. Cycles repeat every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients receive glofitamab intravenously (IV) over 2-4 hours on days 8 and 15 of cycle 2 and then on day 1 of cycles 3-13. Cycles repeat every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive obinutuzumab IV over 4 hours on cycle 2 day 1 and 2. Additionally, patients undergo echocardiography during screening, bone marrow biopsy on study, and computed tomography (CT) scans, fludeoxyglucose F-18 (FDG) positron emission tomography (PET)/computed tomography (CT) scans or magnetic resonance imaging (MRI), and blood sample collection throughout the study. After completion of study treatments, patients are followed up every 3 months for up to 2 years.

Conditions

• Mantle Cell Lymphoma

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy
PROCEDURE	Computed Tomography	Undergo CT scan or FDG PET/CT
PROCEDURE	Echocardiography	Undergo echocardiography
PROCEDURE	FDG-Positron Emission Tomography	Undergo FDG PET/CT
BIOLOGICAL	Glofitamab	Given IV
DRUG	Ibrutinib	Given PO
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
BIOLOGICAL	Obinutuzumab	Given IV

Timeline

• Start date: 2025-05-29
• Primary completion: 2027-11-01
• Completion: 2029-11-01
• First posted: 2024-04-10
• Last updated: 2026-01-30

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study