This phase I/II trial tests the safety, side effects, best dose and effectiveness of golcadomide in combination with rituximab in treating patients with mantle cell lymphoma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Golcadomide may help block the formation, growth or spread of cancer cells. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving golcadomide in combination with rituximab may better treat patients with relapsed or refractory mantle cell lymphoma.
PRIMARY OBJECTIVES: I. To evaluate the safety and tolerance of golcadomide in mantle cell lymphoma (MCL) patients who were resistant or intolerant to covalent bruton's tyrosine kinase inhibitors (cBTKi). II. To evaluate the safety and tolerance of golcadomide in combination with rituximab in MCL patients who were resistant or intolerant to cBTKi. III. To estimate the efficacy of golcadomide and rituximab in MCL patients who were resistant or intolerant to cBTKi. SECONDARY OBJECTIVES: I. To evaluate the complete response rate (CR) of the combination of golcadomide and rituximab. II. To evaluate the durability of response by the duration of response (DOR) and duration of complete response (DOCR). EXPLORATORY OBJECTIVES: I. Correlate clinical response with changes in baseline T cell characteristics and cytokine profiles. II. To measure the rate of minimal residual disease undetectability in responding patients. OUTLINE: This is a phase I, dose-escalation study of golcadomide followed by a phase II study. Patients are assigned to 1 of 2 phases. PHASE I: Patients receive golcadomide orally (PO) once daily (QD) on days 1-14 of each cycle. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and positron emission tomography (PET)/computed tomography (CT) throughout the trial. Patients undergo bone marrow biopsy and may undergo tissue biopsy on study. PHASE II: Patients receive golcadomide PO QD on days 1-14 of each cycle. Patients also receive rituximab intravenously (IV) on days 1, 8, 15 and 22 of cycle 1 and then day 1 of even cycles. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and PET/CT throughout the trial. Patients undergo bone marrow biopsy and may undergo tissue biopsy on study. After completion of study treatment, patients are followed up at 30 days, and then up to 3 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
58
Undergo tissue biopsy
Undergo blood sample collection
Undergo bone marrow biopsy
Undergo PET/CT
Given PO
Undergo PET/CT
Given IV
City of Hope Medical Center
Duarte, California, United States
Incidence of dose limiting toxicities (DLT)
The adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v 5.0). Toxicity will be summarized by type, severity, and attribution. DLT will be individually described.
Time frame: During cycle 1 (Cycle length = 28 days)
Maximum tolerated dose (MTD) of golcadomide
If single agent is tolerable, we will subsequently explore golcadomide in combination with rituximab.
Time frame: Up to 3 years
MTD of golcadomide in combination with rituximab
Patients would remain on therapy until unacceptable toxicity, treating physician discretion or PD.
Time frame: Up to 3 years
Overall response rate (ORR)
Defined as achieving a best response of either complete metabolic response (CMR) or partial metabolic response (PMR) in a response-evaluable participant after the start of protocol therapy and prior to disease progression and/or start of other anti-lymphoma therapy. ORR will be estimated by binary proportions, along with the 95% exact binomial confidence intervals.
Time frame: Up to 3 years
Progression free survival (PFS)
PFS will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error; 95% confidence interval will be constructed based on log-log transformation.
Time frame: From start of protocol treatment to time of disease relapse/progression or death due to any cause, whichever occurs earlier, assessed up to 3 years
Incidence of adverse events
Will be graded by NCI CTCAE v 5.0. Toxicity will be summarized by type, severity, and attribution.
Time frame: Up to 3 years
Duration of response (DOR) of the combination of golcadomide and rituximab
DOR will be estimated using the product-limit method of Kaplan and Meier.
Time frame: From the first achievement of PMR or CMR to time of progressive disease (PD) or death, whichever earlier, assessed up to 3 years
Duration of complete response (DOCR) of the combination of golcadomide and rituximab
DOCR will be estimated using the product-limit method of Kaplan and Meier.
Time frame: Time from the first achievement of CMR to time of PD or death, whichever earlier, assessed up to 3 years
Complete response (CR) of the combination of golcadomide and rituximab
CR rate will be estimated by binary proportions, along with the 95% exact binomial confidence intervals.
Time frame: Up to 3 years
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