Phase 2 Trial of Elranatamab With Cyclophosphamide in Relapsed/Refractory Multiple Myeloma
The purpose of this study is to find out whether the combination of elranatamab and cyclophosphamide is an effective treatment for people with relapsed/refractory multiple myeloma (MM) who have risk factors that may affect how well their disease would respond to elranatamab alone.
• Documentation of Disease:
‣ Patients must have pathologically confirmed diagnosis of multiple myeloma (MM) as defined according to 2014 IMWG criteria.
⁃ Measurable disease defined by at least 1 of the following:
⁃ Serum M-protein ≥0.5 g/dL by SPEP
⁃ Serum immunoglobulin free light chain ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda free light chain ratio (\<0.26 or \>1.65)
⁃ Urinary M-protein excretion ≥200 mg/24 hours by UPEP
⁃ Bone marrow plasma cell percentage (in aspirate or biopsy, whichever is higher) of ≥30%
⁃ Myeloma bone lesion or plasmacytoma lesion with a single diameter of ≥2 cm
• Adverse risk features defined as having ≥1 of the following:
‣ Presence of extramedullary myeloma identifiable by 18F-FDG PET/CT
⁃ Serum beta-2-microglobulin (B2M) level ≥5.5 mg/dL
⁃ Bone marrow plasma cell percentage (in aspirate or biopsy, whichever is higher) of ≥50%
• Prior Treatment Exposure:
‣ Participants have received at least 1 prior lines of therapy for MM including:
• At least 1 IMiD (thalidomide, lenalidomide or pomalidomide)
• At least 1 PI (bortezomib, carfilzomib or ixazomib)
• At least 1 anti-CD38 monoclonal antibody (daratumumab or isatuximab)
• Age ≥ 18
• ECOG Performance Status ≤ 2 (See Appendix I for performance status criteria)
• Not Pregnant and Not Nursing
‣ The effects of elranatamab and cyclophosphamide on the developing human fetus are unknown. For this reason and because cyclophosphamide as well as other therapeutic agents used in this trial are known to be teratogenic, participants of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) during study therapy and for 6 months following the completion of study therapy. Should a participant become pregnant or suspect pregnancy while participating in this study, they should inform their treating physician immediately.
• Required Organ Function:
‣ Adequate hematologic function defined as follows:
• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3(use of G-CSF is permitted if completed at ≥7 days prior to planned start of study treatment)
• Platelets ≥ 25,000 cells/mm3 (transfusion support is permitted)
• Hemoglobin ≥ 8 g/dl (transfusion support is permitted)
‣ Adequate renal function defined as follows:
• Creatinine clearance (CrCL) of ≥15 mL/min by the CKD-EPI formula, Cockcroft-Gault formula, or with direct measurement.
‣ Adequate hepatic function defined as follows:
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x ULN may be enrolled)
• AST and ALT ≤3 x institutional ULN
‣ Adequate cardiac function defined as follows:
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function (see exclusionary cardiac conditions below)