A Phase I/II Study of the Safety, Tolerability and Efficacy of Belantamab Mafodotin (GSK2857916) in Combination With Iberdomide (CC-220)/Dexamethasone Versus Belantamab Mafodotin (GSK2857916)/Dexamethasone in Relapsed Refractory Multiple Myeloma
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.
‣ No evidence of active mucosal or internal bleeding.
‣ No known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to belamaf or drugs chemically related to belamaf, or any of the components of the study treatment.
‣ Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes) or active plasma cell leukemia at the time of screening.
‣ Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study. Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment. Participant must not have current corneal epithelial disease except mild changes in corneal epithelium. For belantamab mafodotin, concomitant administration with strong inhibitors of OATP should be avoided.
‣ RE-REGISTRATION ELIGIBILITY CRITERIA: Patients must meet criteria for progression of myeloma as defined by IMWG criteria indicated as any of the following:
⁃ ≥ 25% increase in M-protein (must be at least 0.5 g/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 not due to other causes. In the absence of progression by serum M protein or free light chain, biopsy of new plasmacytoma of extramedullary disease is warranted.
• If refractory myeloma, it should be defined by IMWG criteria as disease which has become non-responsive or progressive on belamaf/dexamethasone.
‣ RE-REGISTRATION ELIGIBILITY CRITERIA: Measurable disease defined by IMWG criteria as:
⁃ Serum M-protein ≥ 0.5 g/dL.
• Urine monoclonal protein ≥ 200 mg/24h.
• Serum FLC assay: Involved FLC level ≥ 10 mg/dl (≥ 100 mg/l) and serum free light chain ratio is abnormal.
• PET/CT or MRI findings consistent with (c/w) disease progression.
‣ RE-REGISTRATION ELIGIBILITY CRITERIA: Absolute neutrophil count (ANC) ≥ 1,000/mm\^3.
‣ RE-REGISTRATION ELIGIBILITY CRITERIA: Platelet Count ≥ 75,000/mm\^3 (or ≥ 50,000/mm\^3 if BM plasma cells \> 50%).
‣ RE-REGISTRATION ELIGIBILITY CRITERIA: Calc. creatinine clearance ≥ 30 mL/min using Cockcroft-Gault equation.
‣ RE-REGISTRATION ELIGIBILITY CRITERIA: Total bilirubin ≤ 2 mg/dL.
‣ RE-REGISTRATION ELIGIBILITY CRITERIA: AST/ALT ≤ 2.5 x upper limit of normal (ULN).
‣ RE-REGISTRATION ELIGIBILITY CRITERIA: Alkaline phosphatase ≤ 3 x ULN.