Recruiting
Phase 3

Isatuximab, Iberdomide, Bortezomib, Dexamethasone

Sponsor:

Dana-Farber Cancer Institute

Code:

NCT07624513

Conditions

Multiple Myeloma

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Isatuximab

Iberdomide

Bortezomib (B)

Dexamethasone

Melphalan

Study Details

Brief summary:

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 (NDMM). 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.

Conditions

Multiple Myeloma

Study ID

NCT07624513

Start date

Aug 31, 2026

Status verified date

Oct, 2026

Completion date

Mar 1, 2038

Anticipated

Primary completion date

Oct 1, 2033

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • N- NDMM based on IMWG criteria with clonal bone marrow plasma cells ≥10% or biopsy proven bony or extramedullary disease/plasmacytoma (EMD) with any one or more CRAB-features or myeloma defining events (Rajkumar, 2024) (See Appendix E)
  • \- Age 18 - 75 years. (Patients aged 71-75 years who are deemed transplant-eligible by investigator may be enrolled after discussion with and approval from the Sponsor - Investigator)
  • \- Eligible for HDM-ASCT, at time of registration per investigator's assessment, and willing to defer HDM-ASCT if in Cohort 1 or be randomized to HDM-ASCT vs. linvoseltamab if in Cohort 2 (Cohort assignment may not be known until after induction therapy)
  • \- Bone marrow analysis with cytogenetic risk status established by fluorescence in situ hybridization (FISH) and NGS with TP53 by PlasmaSEQ at screening and positive identification of B-cell Clonality (ID) conducted by Adaptive Biotechnologies clonoSEQ® assay

  • Qualified archival BMA may be submitted to Adaptive Biotechnologies clonoSEQ® assay.
  • Results from a previously performed clonoSEQ® assay as standard of care may be acceptable if they meet the requirement of B-cell clonality ID.
  • Previously performed BMA for FISH is acceptable if it can establish cytogenetic risk per Section 5.4.2 along with NGS for TP53 by PlasmaSEQ.
  • Results must be within 1 year of screening and be representative of current NDMM. Results older than one year must be approved by the Sponsor-Investigator.
  • Measurable disease defined by at least one of the following:

  • Serum protein electrophoresis (SPEP): Serum M protein ≥0.5 mg/dL
  • Urine protein electrophoresis (UPEP): Urine M protein ≥200 mg/24 hours
  • Serum free light chain (FLC) assay: involved FLC ≥10 mg/dL (≥100 mg/L) and abnormal serum FLC ratio (<0.26 or >1.65)
  • Screening laboratory evaluations meeting the following parameters:

  • Absolute neutrophil count (ANC) ≥1,000 cells/dL (1.0 × 10\^9/L). Growth factor support is not permitted within 10 days \[14 days for pegfilgrastim\], prior to registration
  • Platelet count ≥ 75,000 cells/dL (75 x 109/L) without transfusions required during the 14 days prior to registration
  • Total Bilirubin ≤ 2 X upper limit of normal (ULN) (except patients with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) ≤ 3.0 x ULN
  • Calculated creatinine clearance ≥30 mL/min (See Appendix B)
  • Hemoglobin ≥ 8.0 g/dl (red blood cell \[RBC\] transfusions are permitted)
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (see Appendix A)
  • Ability and willingness to complete HRQoL and PRO-CTCAE® assessments
  • Must be able to take antithrombotic prophylaxis
  • Sexually active IOCBP agree to use protocol-specified contraceptive methods, at least 28 days prior to starting study drug, while taking study drug, including interruptions in study drugs, and for at least 28 days after the last dose of iberdomide, 5 months after isatuximab, 6 months after linvoseltamab and bortezomib, or males (including those who have had a vasectomy), sexually active with IOCBP, agree to use protocol specified contraceptive methods while taking study drug, including interruptions in study drug and for at least 28 days after the last dose of iberdomide, 5 months after isatuximab, 6 months after linvoseltamab and bortezomib according the PPP (See Appendix G)
  • All patients (male and female with or without childbearing potential) agree to counseling according to the PPP and to abstain from donating blood products for at least 28 days after the last dose of iberdomide and semen or sperm while taking study drug and for at least 28 days after the last dose of iberdomide according to the PPP (See Appendix G) and for 3 months after the last dose of isatuximab, 6 months after the last dose of linvoseltamab and bortezomib
  • Both men and women of all races and ethnic groups are eligible for this trial.

Exclusion Criteria:

  • Prior therapy for MM. Patients may have received:

  • Corticosteroids for management of MM not exceeding the equivalent of 160 mg of dexamethasone in a 2-week period and without change in dosing requirements within 7 days prior to registration
  • Focal palliative radiation for the management of bone pain ≥ 7 days prior to registration
  • Treatment for smoldering multiple myeloma (SMM) if the prior treatment was not an anti-CD38 or anti-BCMA-based therapy:
  • Patients with a prior history of serious allergic reactions associated with thalidomide, lenalidomide, or pomalidomide should not receive iberdomide as they could be at higher risk of hypersensitivity
  • Resolution of symptoms of prior treatment to ≤ grade 1or baseline
  • Known intolerance to steroid therapy
  • Central nervous system (CNS) involvement of MM
  • History of progressive multifocal leukoencephalopathy (PML), known or suspected PML, or history of a neurocognitive condition, CNS movement disorder, history of seizure within 12 months prior to enrollment
  • Peripheral neuropathy grade ≥3, or grade 2 with pain on clinical exam during screening period
  • Prior history of malignancies, other than MM, will be excluded unless the participant has been free of the disease for ≥ 3 years, except for the following non-invasive malignancies: basal or squamous cell skin carcinoma, carcinoma in situ of the cervix, carcinoma in situ of the breast, incidental histological findings of prostate cancer (T1a or T1b using the TNM clinical staging system), or prostate cancer that is curative
  • Any medical or psychiatric illness that in the investigator's opinion would impose excessive risk or would adversely affect patient participation
  • Concurrent uncontrolled cardiovascular conditions (uncontrolled hypertension \[HTN\], uncontrolled arrhythmias, congestive heart failure \[CHF\], unstable angina, grade 3 thromboembolic event or myocardial infarction in the past 6 months)
  • Concurrent symptomatic amyloidosis or plasma cell leukemia
  • POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes)
  • Pregnant or breast feeding female or female who intends to become pregnant during the study
  • Seropositive for human immunodeficiency virus (HIV-1), chronic or active hepatitis B (defined as positive hepatitis B surface antigen \[HepBSAg\] or Hepatitis B core antibody \[HepBcore Ab\]) or hepatitis C (Hep C Ab), or acute hepatitis A; if any history of exposure to hepatitis B or C, then PCR should be negative
  • History of tuberculosis or systemic fungal disease
  • Concurrent active infection requiring therapeutic treatment
  • Lack of clonal identification by Adaptive Biotechnologies clonoSEQ® test

Study Design

Enrollment

720 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

other: Arm A (Induction and screening)

All enrolled participants begin with Step 1 induction that consists of eight 28-day cycles before end-of-induction cohort assignment. Peripheral Blood Stem Cells (PBSC) mobilization/collection is planned after completion of 4-6 cycles of induction for participants without disease progression. End-of-induction MRD/response and cytogenetic risk status determine whether participants proceed to post-induction 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 Complete Response (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 (very good partial response) at Step 3 evaluation \[unless Progressive Disease (PD)\], 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: High-Dose Melphalan followed by Autologous Stem Cell Transplantation (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. Standard Risk (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.

Interventions

Isatuximab

Supplied by Sanofi-Aventis (Sanofi); used in induction and maintenance/consolidation strategies in this protocol; administered subcutaneously (SC) in the maintenance tables provided; not administered in Arm C.

Iberdomide

Supplied by Bristol Myers Squibb/Celgene (BMS); used across induction and maintenance phases; administered orally.

Bortezomib (B)

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

Commercial supply; used in induction; may be administered intravenously or orally at investigator discretion; excluded from Arm G.

Melphalan

Commercial supply; used as conditioning therapy for Arm E before PBSC infusion/ASCT; administered intravenously.

Linvoseltamab

Supplied by Regeneron; used in Arm F consolidation for 8 cycles before maintenance therapy.

On Body Delivery System (OBDS)

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.

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. ]
  • 1-Year MRD-Negative CR Rate [Cohort 2] (Step 2) [ Time Frame: Assessed 1-year after Step 2 consolidation randomization. ]

Central Contacts and Locations

Central contacts

Clifton C. Mo, MD

617-582-7969Clifton_Mo@dfci.harvard.edu

Locations

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

Clifton C. Mo, MD

617-582-7969Clifton_Mo@dfci.harvard.edu

Principal Investigator:

Clifton C. Mo, MD

More Information

Sponsor

Dana-Farber Cancer Institute

Last update posted

Oct 9, 2026

Last verified

Oct, 2026

Keywords

  • Multiple Myeloma

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-10. This information was provided to ClinicalTrials.gov by Dana-Farber Cancer Institute on 2026-10-09. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.