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
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.
Arms & interventions
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureBone Marrow Biopsy
Undergo bone marrow biopsy
- ProcedureComputed Tomography
Undergo CT scan or FDG PET/CT
- ProcedureEchocardiography
Undergo echocardiography
- ProcedureFDG-Positron Emission Tomography
Undergo FDG PET/CT
- BiologicalGlofitamab
Given IV
- DrugIbrutinib
Given PO
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- BiologicalObinutuzumab
Given IV
Outcome measures
Primary
Incidence of dose-limiting toxicities (DLT)
The incidence and type of DLT will be reported. Descriptive statistics will be used to report AEs.
Time frame: 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.
Time frame: 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
Incidence of grade 3 or above adverse events (AEs)
Time frame: Cycle 1 Day 1 to 30 days after last dose of any study drug
Proportion of patients treated with tocilizumab (TCZ)
Time frame: Cycle 1 Day 1 to 30 days after last dose of glofitamab (Glt)
Number of doses of TCZ per participant
Time frame: Cycle 1 Day 1 to 30 days after last dose of Glt
Objective response rate (ORR)
Time frame: 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)
Time frame: Cycle 1 Day 1 to first date of documented progression or death due to any cause, up to 3 years
Duration of response (DOR)
Time frame: At date of first documented CR/PR to date of progression or death due to any cause, up to 3 years
Duration of complete response (DOCR)
Time frame: At date of first documented complete response to first documented progression or death due to any cause, up to 3 years
Eligibility criteria
Study locations (1)
OHSU Knight Cancer Institute
Portland, Oregon, 97239