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

NCT06357676 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY00025355NCI-2024-01208
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicities (DLT)

  The incidence and type of DLT will be reported. Descriptive statistics will be used to report AEs.

  At start of cycle 2 day 1 to end of Cycle 3 (each cycle is 21 days)

• Proportion of participants who achieve a complete response (CR)

  The proportion of patients that achieve a CR will be reported with 95% exact confidence interval (CI). Response to treatment will be evaluated using positron emission tomography/computed tomography (CT) or CT studies and assessed according to Lugano criteria.

  Start of treatment (Cycle 1 Day 1) to date of first CR, documented at any on-treatment or end-of-treatment (EOT) disease assessment, up to 3 years

Secondary Outcomes (7)

• Incidence of grade 3 or above adverse events (AEs)

  Cycle 1 Day 1 to 30 days after last dose of any study drug

• Proportion of patients treated with tocilizumab (TCZ)

  Cycle 1 Day 1 to 30 days after last dose of glofitamab (Glt)

• Number of doses of TCZ per participant

  Cycle 1 Day 1 to 30 days after last dose of Glt

• Objective response rate (ORR)

  Cycle 1 Day 1 to date of first CR or partial response (PR), documented at any On Treatment or EOT disease assessment, up to 3 years

• Progression-free survival (PFS)

  Cycle 1 Day 1 to first date of documented progression or death due to any cause, up to 3 years

Study Arms (1)

Treatment (glofitamab, ibrutinib, obinutuzumab)

EXPERIMENTAL

Patients receive ibrutinib PO 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 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 CT scans, FDG PET/CT scans or MRI, and blood sample collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Procedure: Echocardiography; Procedure: FDG-Positron Emission Tomography; Biological: Glofitamab; Drug: Ibrutinib; Procedure: Magnetic Resonance Imaging; Biological: Obinutuzumab

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Treatment (glofitamab, ibrutinib, obinutuzumab)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

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

Treatment (glofitamab, ibrutinib, obinutuzumab)

Computed Tomography PROCEDURE

Undergo CT scan or FDG PET/CT

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

Treatment (glofitamab, ibrutinib, obinutuzumab)

Echocardiography PROCEDURE

Undergo echocardiography

Also known as: EC

Treatment (glofitamab, ibrutinib, obinutuzumab)

FDG-Positron Emission Tomography PROCEDURE

Undergo FDG PET/CT

Also known as: FDG, FDG-PET, FDG-PET Imaging

Treatment (glofitamab, ibrutinib, obinutuzumab)

Glofitamab BIOLOGICAL

Given IV

Also known as: Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody RO7082859, RO 7082859, RO7082859

Treatment (glofitamab, ibrutinib, obinutuzumab)

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Treatment (glofitamab, ibrutinib, obinutuzumab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (glofitamab, ibrutinib, obinutuzumab)

Obinutuzumab BIOLOGICAL

Given IV

Also known as: Anti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva, huMAB(CD20), R7159, RO 5072759, RO-5072759, RO5072759

Treatment (glofitamab, ibrutinib, obinutuzumab)

Eligibility Criteria

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

You may not qualify if:

• Previous MCL-directed treatment. Treatment with corticosteroids (up to 20 mg dexamethasone or equivalent daily) is allowed prior to and during the screening period for patients with aggressive clinical behavior. All steroids used for disease control must be discontinued within 7 days before starting study treatment except for doses ≤ 20 mg per day of prednisone or equivalent. Ongoing steroids as premedications or for cytokine release syndrome (CRS) management are allowed on study
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
• History of prior malignancy except for the following:
• Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening and felt to be at low risk for recurrence by treating physician
• Persons with low grade prostate cancer on a watch and wait strategy are eligible
• Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled nonmelanomatous skin cancer
• Adequately treated carcinoma in situ without current evidence of disease
• Ongoing hormonal therapy alone for prior malignancy is allowed
• Concurrent use of cytotoxic chemotherapy; radiotherapy; immunotherapy; hormone therapy (other than contraceptives, hormone-replacement therapy, or megestrol acetate); and biologic agents (other than hematopoietic growth factors, if clinically indicated and used in accordance with manufacture and Investigator recommendations), unless approved by the investigator
• Received systemic immunosuppressive medications (e.g., cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to obinutuzumab infusion with the exception of those described
• Known history of hypersensitivity to
• Humanized or murine monoclonal antibodies or products
• A CD3 and / or CD20 antibody
• Glofitamab
• Ibrutinib

Sponsors & Collaborators

• Oregon Health and Science University: collaborator
• Genentech, Inc.: collaborator
• OHSU Knight Cancer Institute: lead

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

Specimen Handling; Biopsy; glofitamab; ibrutinib; Magnetic Resonance Spectroscopy; obinutuzumab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Stephen E Spurgeon

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 2, 2024
• First Posted: April 10, 2024
• Study Start: May 29, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2029
• Last Updated: January 30, 2026

Record last verified: 2026-01

Locations

US (1)