Phase II Clinical Trial of Mezigdomide/Carfilzomib/Dexamethasone (MeziKD) in Patients With Relapsed or Refractory Multiple Myeloma (MM) With Extramedullary Disease (EMD)
This phase II trial studies how well mezigdomide/carfilzomib/dexamethasone (MeziKD) works 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) and have tumors from myeloma cells outside the bone marrow in the soft tissues or organs of the body (extramedullary disease \[EMD\]). Mezigdomide blocks important processes in myeloma cells and may lead to modulation of the immune system, including activation of T-lymphocytes, and downregulation of the activity of other proteins, some of which play key roles in the proliferation of certain cancer cell types. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Dexamethasone is a type of corticosteroid and is used to kill myeloma cells. It is used with other drugs to treat multiple myeloma. Giving MeziKD may kill more cancer cells in patients with relapsed/refractory multiple myeloma (RRMM) with EMD.
• Age ≥ 18 years of age
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• RRMM patients with one or more prior lines of therapy with at least one ES or PS lesion that is accessible to a biopsy. Accessibility will be assessed by the MM tumor board
• Measurable disease meeting at least one of the following:
‣ Serum M-protein ≥1 g/dL
⁃ Urine M-protein ≥200 mg/24 h
⁃ Serum FLC assay: involved FLC level ≥10 mg/dL provided serum FLC ratio is abnormal
⁃ Up to 10 patients without measurable disease can be enrolled but screening imaging and/or bone marrow biopsy have to confirm RRMM. Follow-up response assessment will be performed with imaging using RECIST 1.1 and Deauville Criteria and bone marrow biopsies
• Absolute neutrophil count: ≥ 1 x 10\^9/L
• Platelets: ≥ 75 x 10\^9/L
• Total bilirubin: ≤ 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]): ≤ 3 x ULN
• Renal function: Estimated creatinine clearance ≥ 30 mL/min (Cockroft-Gault)
• Adequate cardiac pump function with a left ventricular ejection fraction of ≥ 40%
• Women of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for at least 28 days after the last dose of mezigdomide or 6 months after the last dose of carfilzomib. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Male patients (non-vasectomized) must agree to use contraception during the treatment period and for at least 28 days after the last dose of mezigdomide or 3 months after the last dose of carfilzomib and refrain from donating sperm during this period
• Participant must understand the investigational nature of this study and sign an independent ethics committee/institutional review board approved written informed consent form prior to receiving any study related procedure