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Active enrolling
United States
EXPERIMENTAL: Arm A (Elranatamab + Daratumumab)
Participants will receive step up dosing of Elranatamab subcutaneously in first cycle followed by weekly dosing for the remainder of the cycle 1. In cycle 2 and 3, elranatamab will be administered every two weeks (Consolidation portion). This will be followed by elranatamab every 4 weeks for 12 cycles in the Maintenance 1 portion. Daratumumab will be given subcutaneously at a fixed dose every 4 weeks starting at Cycle 2 and 3 of Consolidation and for 12 cycles in the Maintenance 1 portion of the study. After completion of Maintenance 1, participants with MRD negativity will receive Elranatamab monotherapy every 4 weeks for additional 12 cycles in Maintenance 2 portion. Participants with MRD positivity will proceed to Arm A1. Participants will undergo therapy in the assigned arm until disease progression, permanent discontinuation (irrespective of reason), death or completion of planned therapy. Cycles will be 28 days. Consolidation consists of 3 cycles; Maintenance 1 consists of 12
DRUG: Elranatamab
Participants 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.DRUG: Daratumumab
Participants will be given 1800 mg of Daratumumab subcutaneously every 4 weeks for up a maximum of 26 cycles.ACTIVE_COMPARATOR: Arm B (ASCT + lenalidomide/daratumumab)
Participants will undergo ASCT according to standard of care institutional practices in the Consolidation portion of the study followed by twelve 28-day cycles of Lenalidomide and Daratumumab in the Maintenance 1 portion. After completion of Maintenance 1, participants with MRD negativity will receive Lenalidomide monotherapy for additional 12 cycles in Maintenance 2 portion. Participants with MRD positivity will proceed to Arm B1. Participants will undergo therapy in the assigned arm until disease progression, permanent discontinuation (irrespective of reason), death or completion of planned therapy. Cycles will be 28 days. Consolidation consists of ASCT; Maintenance 1 consists of 12 cycles; Maintenance 2 consists of 12 cycles. Up to 50 participants will be enrolled to this arm.
DRUG: Daratumumab
Participants will be given 1800 mg of Daratumumab subcutaneously every 4 weeks for up a maximum of 26 cycles.DRUG: Lenalidomide
Participants 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.PROCEDURE: autologous stem cell transplantation
Participants will undergo ASCT as standard treatment following individual site's processes and practices.EXPERIMENTAL: Arm A1 (Late Intensification)
Participants randomized to Arm A that have MRD positivity after Maintenance 1 will undergo ASCT according to standard of care institutional practices followed by twelve 28-day cycles of maintenance treatment with Lenalidomide and Daratumumab in the Late Intensification portion of the study.
DRUG: Daratumumab
Participants will be given 1800 mg of Daratumumab subcutaneously every 4 weeks for up a maximum of 26 cycles.DRUG: Lenalidomide
Participants 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.PROCEDURE: autologous stem cell transplantation
Participants will undergo ASCT as standard treatment following individual site's processes and practices.EXPERIMENTAL: Arm B1 (Late Intensification)
Participants randomized to Arm B that have MRD positivity after Maintenance 1 will receive Elranatamab in combination with Daratumumab for three 28-day cycles as consolidation, followed by Elranatamab in combination with Daratumumab for additional twelve 28-day cycles of maintenance treatment in the Late Intensification portion of the study.
DRUG: Elranatamab
Participants 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.DRUG: Daratumumab
Participants will be given 1800 mg of Daratumumab subcutaneously every 4 weeks for up a maximum of 26 cycles.Rate of MRD negativity after completion of Maintenance 1
Rate of participants with MRD negativity (defined as \
At 60 weeks
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 \
60 weeks or 108 weeks, respectively
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 \
5 years
Incidence of adverse events
Number of participants with adverse events as assessed by common terminology criteria for adverse events (CTCAE) v5.0.
5 years
Rate of MRD negativity at any point in Arm A1
Rate of participants with MRD negativity (defined as \
72 weeks and 120 weeks, respectively
Rate of MRD negativity at any point in Arm B1
Rate of participants with MRD negativity (defined as \
72 weeks and 120 weeks, respectively
International Myeloma Working Group (IMWG) Frailty Index- Comparison in participant report outcomes from baseline to end of treatment
Comparison in participant report outcomes from baseline to end of treatment. Frailty score (range 0-5) and categorizes participants into fit (score = 0), intermediate-fit (score = 1) and frail (score ≥ 2).
4 years
European Organisation for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire (QLQ)-C30- MY20 module- Comparison in participant report outcomes from baseline to end of treatment
Quality of life questionnaire. Version QLQ-C30. Disease specific module MY-20. Scores are based on a 0-100 scale, with higher scores generally indicating better health-related quality of life.
4 years
Patient-Reported Outcomes Measurement Information System (PROMIS)- Comparison in participant report outcomes from baseline to end of treatment
Patient-reported overall health and quality of life questionnaire. Global 10 version. The possible score ranges from 0 to 20 points in each case. 0 points represent the patient's most severe physical and/or mental impairment, while 20 points represent the best possible state of health.
4 years
100
Sponsor: SCRI Development Innovations, LLC
Collaborator: Pfizer, coMMit, Myeloma Trials, Innovated
For more information, call or email the Pfizer Clinical Trial Contact Center:
When calling, please reference this study number: