Determination 2 - Isatuximab, Iberdomide, Bortezomib and Dexamethasone Induction, Followed by Risk- and Response-Adapted Consolidation and Maintenance Therapy, in Transplant-Eligible Patients With Newly Diagnosed Multiple Myeloma

Conditions

• Multiple Myeloma

Eligibility Criteria

Sex

ALL

Age

18 Years - 75 Years

Healthy Volunteers

Not accepted

Interventions

• Isatuximab — DRUG
  Supplied by Sanofi-Aventis (Sanofi); used in induction and maintenance/consolidation strategies in this protocol; administered subcutaneously in the maintenance tables provided; not administered in Arm C.
• Iberdomide — DRUG
  Supplied by Bristol Myers Squibb/Celgene (BMS); used across induction and maintenance phases; administered orally.
• Bortezomib (B) — DRUG
  Commercial supply; used in induction and Arm G maintenance; administered subcutaneously in Arm G on Days 1 and 15 of each 28-day cycle.
• Dexamethasone — DRUG
  Commercial supply; used in induction; may be administered intravenously or orally at investigator discretion; excluded from Arm G.
• Melphalan — DRUG
  Commercial supply; used as conditioning therapy for Arm E before PBSC infusion/ASCT; administered intravenously.
• Linvoseltamab — DRUG
  Supplied by Regeneron; used in Arm F consolidation for 8 cycles before maintenance therapy.
• On Body Delivery System (OBDS) — DEVICE
  Device: On Body Delivery System (OBDS) - Sanofi-Aventis device used with isatuximab administration; abdominal/periumbilical single-site application with post-dose needle retraction and lock-out.

Study Details

The purpose of the study is to determine the best treatment approach based on the risk profile of the cancer cells and on how the disease responds to treatment. This is a randomized research study evaluating treatment for transplant-eligible participants with newly diagnosed multiple myeloma. Induction therapy in this study includes the drugs isatuximab, iberdomide, bortezomib, and dexamethasone. After induction therapy, participants will receive consolidation and maintenance therapy that is adapted based on their risk profile and response to treatment. The research study procedures include: screening for eligibility, study visits, blood and bone marrow tests, disease assessments, treatment with study drugs, and follow-up visits. It is expected that about 720 participants will take part in this study.

Key Dates

Start date

Jun 8, 2026

Status verified

May 2026

Primary completion

Oct 1, 2033

Completion

Mar 1, 2038

Study Design

Enrollment

720 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Other: Arm A (Induction and screening)
  All enrolled participants begin with Step 1 induction for 8 28-day cycles before end-of-induction cohort assignment. PBSC mobilization/collection is planned between Cycles 4-6 for participants without progression. End-of-induction MRD/response and risk status determine whether participants proceed to Cohort 1 or Cohort 2.
• Other: Arm B (Cohort 1 Maintenance Therapy Part 1)
  Participants assigned to Cohort 1 enter Arm B and receive isatuximab + iberdomide maintenance for 36 cycles. Maintenance should begin within 28 days of the last induction cycle.
• Other: Arm C: Cohort 1 Maintenance Therapy (Part 2), Single-Agent Iberdomide
  After completion of Arm B, participants with MRD-negative CR status at Step 3 are assigned to Arm C and continue single-agent iberdomide until progression. Isatuximab is not administered in Arm C.
• Other: Arm D: Cohort 1 Maintenance Therapy (Part 2), Iberdomide + Isatuximab
  After completion of Arm B, participants with MRD-positive or MRD-indeterminate disease, or \<VGPR at Step 3 evaluation (unless PD), continue iberdomide + isatuximab until progression.
• Active Comparator: Arm E: Cohort 2 Randomized Consolidation and Maintenance (HDM-ASCT Strategy)
  Eligible Cohort 2 participants are randomized to Arm E: HDM-ASCT consolidation followed by isatuximab + iberdomide maintenance until progression. The protocol identifies Arm E as the control arm and describes HDM-ASCT-based therapy as the SOC comparator for Cohort 2. Consolidation should begin preferably within 30 days, and no later than 42 days, after induction completion. Maintenance begins 60-110 days after PBSC infusion.
• Experimental: Arm F: Cohort 2 Randomized Consolidation and Maintenance (Linvoseltamab Strategy)
  Eligible Cohort 2 participants are randomized to Arm F: linvoseltamab consolidation for 8 cycles followed by isatuximab + iberdomide maintenance until progression. The protocol explicitly identifies Arm F as the experimental arm and hypothesizes superior efficacy versus Arm E. Maintenance should begin within 2-4 weeks after the last linvoseltamab dose.
• Other: Arm G: Cohort 2 Non-randomized 3-Drug Maintenance
  Participants in Cohort 2 who do not meet criteria for consolidation therapy may enter Arm G. SR MRD-indeterminate participants may also enter Arm G or, with Sponsor-Investigator approval, may be randomized in Cohort 2. Arm G is a 3-drug maintenance regimen continued in 28-day cycles until progression. The protocol explicitly states that dexamethasone is excluded from Arm G.

Primary Outcome Measure

3-Year Sustained Minimal Residual Disease (sMRD)-negative Complete Response (CR) Rate [Cohort 1] (Step 2) [ Time Frame: Assessed after Step 2 maintenance cycle 36 (cycle duration=4 weeks), at 144 weeks/36 months. ]

Central Contacts

• Clifton C. Mo, MD
  617-582-7969
  [email protected]

Locations (3)

Find similar trials in Boston, MA

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