This phase II trial tests the effectiveness of golcadomide and rituximab as bridging treatment before chimeric antigen receptor (CAR) T-cell therapy in patients with aggressive B-cell non-Hodgkin lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Patients that are able to receive CAR T-cell therapy have a potential for cure, however, many will not be qualified to receive therapy due to relapse. Bridging therapy is therapy intended to transition a patient from one therapy or medication to another or maintain their health or status until they are a candidate for a therapy or have decided on a therapy. 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 and rituximab as bridging therapy before CAR T-cell therapy may kill more tumor cells and may improve the chance of proceeding to CAR T-cell therapy in patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma.
PRIMARY OBJECTIVE: I. Evaluate efficacy as measured by the disease control rate (complete metabolic response \[CMR\], partial metabolic response \[PMR\], and no metabolic response \[NMR\]) by Lugano 2014 positron emission tomography (PET)-computed tomography (CT) based assessment after 2 cycles of therapy. SECONDARY OBJECTIVES: I. To further evaluate clinical efficacy as measured by overall response rate (ORR), complete response (CMR) rate, disease control rate by Lugano PET-CT based criteria. II. To evaluate the safety and tolerability of golcadomide + rituximab combination therapy as measured by the incidence and severity of treatment related adverse events (TRAE). III. To evaluate efficacy as a bridging therapy as measured by the number of patients proceeding to CAR-T and response to CAR-T. IV. To evaluate duration of response, progression-free survival, and overall survival. EXPLORATORY OBJECTIVES: I. Improvement of symptoms (compressive, pain, B symptoms \[fever, night sweats, weight loss\]) associated with the disease as determined by the investigator. II. To evaluate the diversity of CAR-T products received in patients proceeding to CAR-T. OUTLINE: Patients receive golcadomide orally (PO) once daily (QD) on days 1-14 of each cycle and rituximab intravenously (IV) on days 1, 8, 15 and 22 of cycle 1 and then on day 1 of all subsequent cycles. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. ELIGIBLE FOR CAR-T: After 2 cycles, patients undergo leukapheresis and may receive 1-2 additional cycles of golcadomide and rituximab prior to undergoing standard of care CAR-T therapy. INELIGIBLE FOR CAR-T: After 2 cycles, patients receive golcadomide PO QD on days 1-14 of each cycle and rituximab IV on day 1 of each cycle. Cycles repeat every 28 days for up to 10 additional cycles of golcadomide (cycles 3-12) and up to 3 additional cycles of rituximab (cycles 3-5) in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and PET/CT or CT throughout the study. Additionally, patients may undergo bone marrow aspiration and biopsy as clinically indicated. After completion of study treatment, patients are followed up at 28 days. CAR-T ineligible patients are followed up every 3 months until progression or subsequent treatment, then every 6 months for up to 2 years. CAR-T eligible patients are followed up at 180 days after CAR-T then every 6 months for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
41
Undergo blood sample collection
Undergo bone marrow aspiration and biopsy
Undergo bone marrow aspiration and biopsy
Undergo standard of care CAR-T therapy
Undergo CT or PET/CT
Given PO
Undergo leukapheresis
Undergo PET/CT
Given IV
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
RECRUITINGMayo Clinic in Florida
Jacksonville, Florida, United States
RECRUITINGMayo Clinic Health System in Albert Lea
Albert Lea, Minnesota, United States
RECRUITINGMayo Clinic Health Systems-Mankato
Mankato, Minnesota, United States
RECRUITINGMayo Clinic in Rochester
Rochester, Minnesota, United States
RECRUITINGMayo Clinic Health System-Eau Claire Clinic
Eau Claire, Wisconsin, United States
RECRUITINGMayo Clinic Health System-Franciscan Healthcare
La Crosse, Wisconsin, United States
RECRUITINGDisease control
Will be defined as a complete metabolic response (CMR), partial metabolic response (PMR), or no metabolic response (NMR) by Lugano 2014 PET-CT.
Time frame: 2 cycles (cycle length = 28 days)
Disease control rate
Will be estimated by the total number of patients who achieve a CMR, PMR, or NMR by Lugano 2014 positron emission tomography (PET)/computed tomography (CT) divided by the total number of evaluable patients.
Time frame: Up to 2 years
Complete response rate
Will be assessed by the total number of patients who achieve a CMR by Lugano 2014 PET/CT.
Time frame: Up to 2 years
Overall response rate
Will be assessed by the total number of patients who achieve a CMR or PMR by Lugano 2014 PET/CT divided.
Time frame: Up to 2 years
The proportion of patients proceeding to chimeric antigen receptor T-cell (CART)
Will be assessed by the total number of patients who proceed to CART divided by the total number of evaluable patients.
Time frame: Up to 2 years
Overall response rate to CART
Will be assessed by the total number of patients who achieve a CMR or PMR by Lugano 2014 PET/CT after CART.
Time frame: Up to 2 years
Duration of response
Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CMR or PMR to first documentation of disease progression.
Time frame: Up to 2 years
Progression-free survival (PFS)
Progression-free survival is defined as the time from registration to first documentation of disease progression (PMD or PD) or death due to any cause in the absence of documented progression
Time frame: Up to 2 years
Overall survival (OS)
Overall survival is defined as the time from registration to death due to any cause.
Time frame: From registration to death due to any cause, assessed up to 2 years
Incidence of adverse events (AEs)
Will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE). The maximum grade for each type of AE will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the AE(s) to the study treatment will be taken into consideration and treatment related AEs will be evaluated.
Time frame: Up to 30 days after last dose of study treatment
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