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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
27
Undergo blood sample collection
Undergo bone marrow biopsy
Undergo CT scan or FDG PET/CT
Undergo echocardiography
Undergo FDG PET/CT
Given IV
Given PO
Undergo MRI
Given IV
OHSU Knight Cancer Institute
Portland, Oregon, United States
RECRUITINGIncidence 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
Incidence of grade 3 or above adverse events (AEs)
The incidence of grade 3 or above AEs will be reported with 95% exact CI.
Time frame: Cycle 1 Day 1 to 30 days after last dose of any study drug
Proportion of patients treated with tocilizumab (TCZ)
The proportion of patients treated with TCZ will be reported with 95% exact CI.
Time frame: Cycle 1 Day 1 to 30 days after last dose of glofitamab (Glt)
Number of doses of TCZ per participant
The number of doses of TCZ per participant will be reported with 95% exact CI.
Time frame: Cycle 1 Day 1 to 30 days after last dose of Glt
Objective response rate (ORR)
ORR (CR + PR) will be defined as the proportion of the efficacy evaluable set that achieves a complete response (CR) or PR at any on-treatment or end of treatment disease assessment. ORR along with 95% CI will be reported.
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)
PFS will be defined as the time from the first dose of study drug to the first date of documented progression or recurrence or death due to any cause, whichever occurs first. PFS will be summarized descriptively using the Kaplan-Meier method. Median PFS and PFS rates will be estimated with 95% CI if possible.
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)
DOR will be estimated using the Kaplan-Meier method. Median DOR will be estimated with 95% CI if possible.
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)
DOCR will be estimated using the Kaplan-Meier method. DOCR will be estimated with 95% CI if possible.
Time frame: At date of first documented complete response to first documented progression or death due to any cause, up to 3 years
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