This phase II trial compares iberdomide maintenance therapy to disease monitoring for improving survival in patients who have received idecabtagene vicleucel (a type of chimeric antigen receptor T-cell \[CAR-T\] therapy) for multiple myeloma. The usual approach after treatment with idecabtagene vicleucel is to monitor the multiple myeloma without giving myeloma medications. There is currently no medication approved specifically for use after idecabtagene vicleucel treatment. Upon administration, iberdomide modifies the immune system and activates immune cells called T-cells, which could enhance the effectiveness of idecabtagene vicleucel. Iberdomide may keep multiple myeloma under control for longer than the usual approach (disease monitoring) after idecabtagene vicleucel, and may help multiple myeloma patients live longer.
PRIMARY OBJECTIVES: I. To establish and confirm the safety and dose of iberdomide as maintenance after idecabtagene vicleucel (ide-cel) CAR-T. (Safety run-in) II. To assess whether iberdomide maintenance therapy after idecabtagene vicleucel CAR-T cell therapy increases progression-free survival (PFS) relative to observation without additional therapy. (Randomized phase II) SECONDARY OBJECTIVES: I. To demonstrate anti-tumor activity, defined as conversion from non-minimal residual disease (MRD) complete response (CR)/stringent CR (sCR) status to MRD-negative CR/sCR, as well as improvement in PFS in the safety run-in cohort. (Safety run-in) II. To estimate the rate of conversion from MRD-positive at baseline to MRD-negative at any time point post-initiation of iberdomide maintenance or observation without additional therapy. (Key secondary objective; Randomized phase II) III. To estimate overall survival (OS) distribution post-initiation of iberdomide maintenance or observation without additional therapy. (Key secondary objective; Randomized phase II) IV. To estimate the minimal residual disease (MRD)-negativity rate at pre-registration and at one year post-initiation of iberdomide maintenance or observation without additional therapy. (Randomized phase II) V. To estimate rate of deepening hematological response among patients with measurable multiple myeloma (MM) post-initiation of iberdomide maintenance or observation without additional therapy. (Randomized phase II) VI. To evaluate the safety profile of iberdomide maintenance. (Randomized phase II) VII. To evaluate the peripheral blood immunophenotype before and during iberdomide maintenance or observation without additional therapy. (Randomized phase II) VIII. To evaluate persistence of CAR-T cells with iberdomide maintenance or observation without additional therapy. (Randomized phase II) CORRELATIVE SCIENCE OBJECTIVES: I. To estimate the minimal residual disease (MRD)-negativity rate at start of maintenance and at one year post-initiation of maintenance or observation. II. To estimate the sustained MRD-negativity rate. III. To estimate the rate of conversion from MRD-positive to MRD-negative. (Key objective) IV. To evaluate the peripheral blood immunophenotype before and during maintenance therapy or observation. V. To evaluate the persistence of CAR-T cells. VI. To evaluate B-cell maturation antigen (BCMA) protein expression by immunohistochemistry on myeloma cells from patients that have relapsed/recurrent disease. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP 1: Patients undergo disease monitoring at monthly clinic visits until disease progression. Patients also undergo bone marrow aspiration and biopsy throughout the trial, undergo collection of blood samples at screening and on study, and undergo positron emission tomography (PET)/computed tomography (CT) and/or skeletal survey x-ray, CT, or magnetic resonance imaging (MRI) at screening and then as clinically indicated. GROUP 2: Patients receive iberdomide orally (PO) once daily (QD) on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy throughout the trial, undergo collection of blood samples at screening and on study, and undergo PET/CT and/or skeletal survey x-ray, CT, or MRI at screening and then as clinically indicated. After completion of study treatment, patients are followed up within 30 days, then every 3-6 months until 4 years following registration.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
84
Undergo collection of blood samples
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Undergo PET/CT and/or CT
Given PO
Undergo MRI
Undergo disease monitoring
Undergo PET/CT
Undergo skeletal survey x-ray
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, United States
Cedars-Sinai Medical Center
Los Angeles, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
Augusta University Medical Center
Augusta, Georgia, United States
Incidence of dose-limiting toxicities (safety run-in)
Time frame: The first 3 months of therapy
Progression-free survival (PFS) (randomized phase II)
Final analyses will use log-rank test statistics to compare the PFS distributions between the treatment arms. Will also evaluate differences in PFS between the treatment arms using a stratified log-rank test. In addition, the methods of Kaplan and Meier will be used to graphically evaluate these distributions as well as to estimate the median PFS and corresponding 95% confidence intervals. Further, will also estimate the 1- and 2-year PFS rates for each treatment arm along with corresponding 95% confidence intervals. Finally, Cox proportional hazards models will be used to evaluate the impact of treatment arm on PFS.
Time frame: From randomization to the time of progression and/or death, assessed up to 4 years
Incidence of adverse events
Adverse events will be collected and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. For CTCAE data, the maximum grade for each type of adverse will be recorded for each patient, and described using frequency tables. All-cause adverse events will be summarized as well as treatment-related adverse events, with particular focus on grade 3+ non-hematologic adverse events and grade 4+ hematologic events. Frequency tables will be reviewed to identify patterns. The overall adverse event severity will be compared between treatment arms using a chi-square test (or Fisher's exact test if the data in contingency table is sparse).
Time frame: Up to 4 years
Number of treatment cycles received (tolerability)
Will be summarized.
Time frame: Up to 4 years
Proportion of patients with dose modifications, omissions, and/or delays (tolerability)
Will be summarized.
Time frame: Up to 4 years
Proportion of patients who go off treatment due to adverse events
Will be summarized.
Time frame: Up to 4 years
Overall survival (OS)
The Kaplan-Meier method will be used to estimate OS for each treatment arm, with 1- and 2-year OS estimates and OS medians along with their 95% confidence intervals. For the comparison of the treatment arms, will use a one-sided log-rank test to compare the OS distributions between treatment arms. Will also evaluate the influence of arm on OS using stratified and unstratified multivariable Cox proportional hazards models.
Time frame: From randomization until death from any cause, assessed up to 4 years
Best response achieved while on study
Will calculate these rates by treatment arm along with corresponding 95% binomial confidence intervals. Logistic regression models may also be used to assess differences in the ability to deepen or convert to a response between treatment arms. Minimal residual disease (MRD) will be assessed as an aspect of response assessment.
Time frame: Up to 4 years
Proportion of patients who improve their status
Will calculate these rates by treatment arm along with corresponding 95% binomial confidence intervals. Logistic regression models may also be used to assess differences in the ability to deepen or convert to a response between treatment arms. MRD will be assessed as an aspect of response assessment.
Time frame: After randomization, up to 4 years
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University of Illinois
Chicago, Illinois, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, United States
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa, United States
Iowa Methodist Medical Center
Des Moines, Iowa, United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, United States
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