This phase I/II trial tests the safety, side effects, best dose, and effectiveness of iberdomide in combination with belantamab mafodotin and dexamethasone in treating patients with multiple myeloma (MM) that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Multiple myeloma is a cancer that affects white blood cells called plasma cells, which are made in the bone marrow and are part of the immune system. Multiple myeloma cells have a protein on their surface called B-cell maturation antigen (BCMA) that allows the cancer cells to survive and grow. Immunotherapy with iberdomide, may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Belantamab mafodotin has been designed to attach to the BCMA protein, which may cause the myeloma cell to become damaged and die. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Iberdomide plus belantamab mafodotin may help slow or stop the growth of cancer in patients with multiple myeloma.
≥ 25% increase in M-protein (must be at least 0.5g/dl above nadir from last treatment regimen).
25% difference between involved and uninvolved serum free light chains from its nadir or
The development of new plasmacytomas or hypercalcemia.
Refractory myeloma as defined by IMWG criteria as disease which become non-responsive or progresses on therapy or within 60 days of last treatment in patients who had achieved a minimal response or better on prior therapy.
None
Sequential
Iberdomide
DrugReceive PO
Belantamab Mafodotin
Biological/VaccineReceive IV
Dexamethasone
DrugReceive PO
Echocardiography
Procedure/SurgeryUndergo ECHO
Computed Tomography
Procedure/SurgeryUndergo CT
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Positron Emission Tomography
Procedure/SurgeryUndergo PET
Bone Marrow Biopsy
Procedure/SurgeryUndergo Bone Marrow Biopsy
Bone Marrow Aspiration
Procedure/SurgeryUndergo Bone Marrow Aspirate
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Maximum tolerated dose (MTD) of iberdomide (Phase I)
MTD will be defined as the highest dose level among those tested where at most one out of 6 patients develops a DLT prior to the start of their second cycle of treatment. Will be assessed by NCI CTCAE v 5.0.
Progression-free survival (PFS) (Phase II)
Will be compared between the two treatment arms. 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.
Rate of grade 3+ Adverse Events (AEs)
Will be collected and graded according to the NCI CTCAE v 5.0 criteria.
Complete response (CR) rate
Will be estimated for each treatment arm and calculated as the number of patients with CR divided by the total number of patients randomized. For each treatment arm, CR rates will be estimated with their 95% confidence intervals.
Overall response rate (ORR)
: Overall response includes complete, very good partial, and partial responses. ORR will be estimated for each treatment arm and calculated as the number of patients with response divided by the total number of patients randomized. For each treatment arm, ORRs will be estimated with their 95% confidence intervals.
Duration of response (DoR)
: DoR will be calculated for patients with a complete, very good partial, or partial response from the first date of response until the earlier of disease progression, death from any cause, or non-protocol myeloma-directed therapy to treat residual or progressive disease. Patients alive and progression-free at the date of last known clinical assessment or at the last assessment date prior to beginning a non-protocol myeloma-directed therapy for reasons other than residual or progressive disease will be censored. The Kaplan-Meier method will be used to estimate duration of response for each treatment arm.
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Alliance for Clinical Trials in Oncology
Lead sponsor
National Cancer Institute (NCI)
Collaborator
