This is an open-label, multi-site, Phase II randomized trial with response-adaptive design for newly diagnosed multiple myeloma (NDMM) participants who have had prior induction therapy. The primary objective of this study is to compare the rates of achieving undetectable measurable residual disease (MRD) in the bone marrow with elranatamab and daratumumab employed as post-induction consolidation and maintenance treatment (Arm A) versus autologous stem cell transplant (ASCT) followed by lenalidomide and daratumumab treatment (Arm B).
Age >18 years with no upper age limit.
Newly diagnosed multiple myeloma with indication for initiation of therapy diagnosed within last 12 months. Pretreatment parameters necessary for disease characterization and response assessment must be available.
Eligible for ASCT according to institutional policy as evaluated by investigator.
Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Appendix A).
Diagnosis of primary light chain amyloidosis, POEMS, Waldenstrom's macroglobulinemia, plasma cell leukemia, or central nervous system (CNS) involvement by MM.
Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients (refer to the elranatamab Investigator's Brochure [IB] and appropriate package inserts).
PI therapy - 14 days.
IMiD agent therapy -14 days.
Sequential
Elranatamab
DrugParticipants will receive step up dosing of Elranatamab subcutaneously in first cycle of consolidation followed by fixed dosing for 2 additional cycles and for 12 cycles in maintenance. Arm A participants will receive additional 12 cycles of Elranatamab monotherapy if they are MRD negative after Maintenance 1 for a total of 27 cycles. Cycles will be 28 days.
Daratumumab
DrugParticipants will be given 1800 mg of Daratumumab subcutaneously every 4 weeks for up a maximum of 26 cycles.
Lenalidomide
DrugParticipants will receive 10 mg of Lenalidomide daily by mouth for 21 days of each 28-day cycle for up to a maximum of 24 cycles.
autologous stem cell transplantation
Procedure/SurgeryParticipants will undergo ASCT as standard treatment following individual site's processes and practices.
Rate of MRD negativity after completion of Maintenance 1
Rate of participants with MRD negativity (defined as \<10-5) after completion of the Maintenance 1 portion of the study.
Rate of sustained MRD negativity after completion of Consolidation and Maintenance 1 or after completion of Maintenance 1 and Maintenance 2
Rate of participants with MRD negativity (defined as \<10-5) after completion of the Consolidation and Maintenance 1 (negative at both timepoints) or after completion of Maintenance 1 and Maintenance 2 (negative at both timepoints).
Event-free survival (EFS)
Median time from randomization until event using Kaplan-Meier estimates. Event is defined as death, disease progression as defined by the International Myeloma Working Group standard response criteria, initiation of alternative regimen (including Arms A1 or B1 due to MRD positivity after Maintenance 1) or resurgence of MRD (i.e. MRD becoming ≥10-5 after prior negative result \<10-5).
Incidence of adverse events
Number of participants with adverse events as assessed by common terminology criteria for adverse events (CTCAE) v5.0.
Rate of MRD negativity at any point in Arm A1
Rate of participants with MRD negativity (defined as \<10-5) after completion of ASCT or after maintenance treatment.
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SCRI Development Innovations, LLC
Lead sponsor
Pfizer
Collaborator
coMMit, Myeloma Trials, Innovated
Collaborator
