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Not yet recruitingNCT07601100IsaIberVDUpdated Sep 3, 2026

Isatuximab, Iberdomide, Bortezomib, Dexamethasone in Transplant Ineligible/Deferred Newly Diagnosed Myeloma

A Phase 1/2 interventional study of Isatuximab and Iberdomide in Newly Diagnosed Multiple Myeloma, sponsored by Dana-Farber Cancer Institute. Not yet recruiting at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-03.

Sponsored by Dana-Farber Cancer Institute · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
88
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

This study is to evaluate the combination of isatuximab, iberdomide, bortezomib, and dexamethasone in newly diagnosed multiple myeloma participants who are transplant ineligible or not intended for upfront transplant.

The names of the study drugs used in this research study are:

isatuximab, iberdomide, bortezomib dexamethasone

Read the detailed description

This is an open-label, Phase 1b/2, multicenter study which will enroll patients with newly diagnosed multiple myeloma (NDMM), who are transplant ineligible or deferred, to induction followed by maintenance therapy. Participants will be registered in HCC CTMS OnCore before receiving any study-specific treatment, and study treatment is expected to begin within 5 days after registration.

The study drugs used in this research include bortezomib, dexamethasone, isatuximab, and iberdomide (CC-220). The U.S. Food and Drug Administration (FDA) has approved bortezomib and dexamethasone for the initial treatment of multiple myeloma. The FDA has approved isatuximab for initial treatment of multiple myeloma in transplant ineligible patients and for myeloma that has returned after prior treatment. The FDA has not approved iberdomide (CC-220) for the treatment of multiple myeloma. The combination of these drugs, used as induction and maintenance therapy in this study, is considered investigational.

The research study procedures include: screening for eligibility, in-clinic visits, urine tests, questionnaires, PET scans, blood tests, electrocardiograms (ECGs), bone marrow aspiration and biopsy, biobanking, and pregnancy tests for participants who are able to become pregnant.

It is expected that about 88 people will take part in this study. Participants are classified and assigned treatment for induction based on baseline age 70 years status and myeloma frailty score and further assigned for maintenance based on baseline International Myeloma Working Group (IMWG)/International Myeloma Society (IMS) genomic risk classification.

02

Conditions studied

  • Newly Diagnosed Multiple Myeloma

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Keywords

  • multiple myeloma
  • newly diagnosed multiple myeloma
03

In context

Multiple Myeloma

3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.

This study's planned enrollment of 88 is above the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.

Browse Multiple Myeloma studies →

Lead sponsor

Dana-Farber Cancer Institute is the lead sponsor of 813 studies on the registry; 124 are open to participants now.

Of its 113 completed or terminated interventional studies of FDA-regulated products, 77 (68%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Male or female, 18 years of age or older
  • Ability to understand and the willingness to sign a written informed consent document
  • 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 G)
  • Ineligible for ASCT as assessed by the treating physician or eligible but prefers and agrees to defer ASCT until after induction and maintenance therapy, upon progression or at a later time

  • Measurable disease defined as at least one of the following:

    • Serum M-protein 0.5 g/dL
    • Urine M-protein 200 mg/24 hours
    • Serum FLC assay: involved FLC 10 mg/dL (100 mg/L) and an abnormal kappa to lambda FLC ratio (\< 0.26 or > 1.65)
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (See Appendix A)

  • Screening Laboratory evaluations with the following parameters:

    • Absolute neutrophil count (ANC) ≥ 1,000 cells/dL (1.0 x 109/L)

      --- Note: Growth factor support is not permitted within 10 days, [14 days for pegfilgrastim], prior to the screening hematologic test.

    • Platelet count ≥ 75,000 cells/dL (75 x 109/L) (without transfusions required during the 3 days prior to the screening hematologic test)
    • Total Bilirubin ≤ 2 X upper limit of normal (ULN) (except patients with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
    • AST (SGOT) and ALT (SGPT) ≤ 3.0 x ULN
    • Calculated creatinine clearance (CrCl) 30ml/min (Appendix B)
    • Hemoglobin ≥ 8.0 g/dl (red blood cell (RBC) transfusions are permitted)
  • Individuals of childbearing potential (IOCBP) must have 2 negative pregnancy tests before initiation of therapy, and agree to ongoing testing, based on the frequency outlined in the Pregnancy Prevention Plan (PPP) (See Appendix H)
  • 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 study drug or males sexually active with IOCBP, (including those who have had a vasectomy), 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 and 6 months after bortezomib, according to the PPP (See Appendix H)
  • 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 abstain from donating 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 H) and for 5 months after the last dose of isatuximab and 6 months after the last dose of bortezomib
  • Must be able to take antithrombotic prophylaxis (See Section 5.9.1)

Exclusion criteria

Exclusion Criteria:

  • Prior therapy for MM. Patients may have received:

    • Corticosteroids for management of MM not to exceed equivalent of 160 mg of dexamethasone in a 2-week period and should be stable 7 days prior to the registration.
    • Focal palliative radiation for the management of bone pain completed ≥ 7 days prior to registration

    • Treatment for smoldering myeloma as long as the prior treatment did not include anti-CD38 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 1 or baseline
  • Known intolerance to steroid therapy
  • Prior history of malignancies, other than MM, will be excluded unless the participant has been free of the disease for ≥ 3 years with the exception of 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 Tumor, Node, Metastasis (TNM) clinical staging system), or prostate cancer that is curative
  • Central nervous system involvement with MM
  • Peripheral neuropathy grade 3, or grade 2 with pain on clinical exam during screening period
  • Any medical or psychiatric illness that in the investigator's opinion would impose excessive risk to the patient or would adversely affect participation
  • Concurrent uncontrolled cardiovascular conditions (uncontrolled hypertension, uncontrolled arrhythmias, congestive heart failure, 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)
  • 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 C (Hep C Ab), or acute hepatitis A. If any history of exposure to hepatitis B or C, then PCR should be negative
  • Pregnant or breast feeding female or IOCBP who intend to become pregnant during the study.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to other agents used in study
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
88 participants (estimated)

Study arms

  • Experimental
    Group A Induction: Age <70 years and Fit (standard-intensity schedule)

    Participants \<70 years of age and considered fit based on the myeloma frailty score of 0. Induction cycles 1-8; 28-day cycles: Isatuximab: 10 mg/kg Intravenous (IV) Days 1, 8, 15, 22 (Cycle 1 only); Days 1,15 (Cycle 2+) Iberdomide: 1 mg or 0.75 mg Oral (PO) Days 1-21 Bortezomib: 1.3 mg/m2 Subcutaneous (SC) Days 1, 8, 15, 22 Dexamethasone: 20 mg IV or PO Days 1, 2, 8, 9, 15, 16, 22, 23

    Drug: Isatuximab · Drug: Iberdomide · Drug: Bortezomib · Drug: Dexamethesone

  • Experimental
    Group B Induction: Age ≥70 years and/or Intermediate Fit/Frail (reduced-intensity schedule)

    Participants ≥70 years of age and/or considered intermediate fitness and frail based on the myeloma frailty score of \>1. Induction cycles 1-8; 28-day cycles: Isatuximab: 10 mg/kg IV Days 1, 8, 15, 22 (Cycle 1 only); Days 1,15 (Cycle 2+) Iberdomide: 1 mg or 0.75 mg PO Days 1-21 Bortezomib: 1.3 mg/m2 SC Days 1, 8, 15 Dexamethasone: 12 mg IV or PO Days 1, 8, 15, 22; 8 mg IV or PO Days 2, 9, 16, 23

    Drug: Isatuximab · Drug: Iberdomide · Drug: Bortezomib · Drug: Dexamethesone

  • Experimental
    Group A Maintenance: High-Risk, Age <70 years and Fit (3-drug schedule)

    Participants high-risk per IMWG/IMS criteria, \<70 years of age, considered fit based on the myeloma frailty score of 0. Maintenance cycles 1-36; 28-day cycles: (for participants with ≥PR after Induction Cycle 8) Isatuximab: 10 mg/kg IV Days 1, 15 Iberdomide: 1 mg or 0.75 mg PO Days 1-21 Bortezomib: 1.3 mg/m2 SC Days 1, 15

    Drug: Isatuximab · Drug: Iberdomide · Drug: Bortezomib

  • Experimental
    Group A Maintenance: Standard-Risk, Age <70 years and Fit (2-drug schedule)

    Participants standard-risk per IMWG/IMS criteria, \<70 years of age, considered fit based on the myeloma frailty score of 0. Maintenance cycles 1-36; 28-day cycles: (for participants with ≥PR after Induction Cycle 8) Isatuximab: 10 mg/kg IV Days 1, 15 Iberdomide: 1 mg or 0.75 mg PO Days 1-21

    Drug: Isatuximab · Drug: Iberdomide

  • Experimental
    Group B Maintenance: High-Risk, Age ≥70 years and/or Intermediate Fit/Frail (3-drug schedule)

    Participants high-risk per IMWG/IMS criteria, ≥70 years of age and/or considered intermediate fitness and frail based on the myeloma frailty score of \>1. Maintenance cycles 1-36; 28-day cycles: (for participants with ≥PR after Induction Cycle 8) Isatuximab: 10 mg/kg IV Days 1, 15 Iberdomide: 1 mg or 0.75 mg PO Days 1-21 Bortezomib: 1.3 mg/m2 SC Days 1, 15

    Drug: Isatuximab · Drug: Iberdomide · Drug: Bortezomib

  • Experimental
    Group B Maintenance: Standard-Risk, Age ≥70 years and/or Intermediate Fit/Frail (2-drug schedule)

    Participants standard-risk per IMWG/IMS criteria, ≥70 years of age and/or considered intermediate fitness and frail based on the myeloma frailty score of \>1. Maintenance cycles 1-36; 28-day cycles: (for participants with ≥PR after Induction Cycle 8) Isatuximab: 10 mg/kg IV Days 1, 15 Iberdomide: 1 mg or 0.75 mg PO Days 1-21

    Drug: Isatuximab · Drug: Iberdomide

Interventions

  • DrugIsatuximab

    Administration, pre-medications and supportive care per protocol

    Also known as: Sarclisa, Isatuximab-irfc

  • DrugIberdomide

    Administration, pre-medications and supportive care per protocol

    Also known as: CC-220

  • DrugBortezomib

    Administration, pre-medications and supportive care per protocol

    Also known as: Velcade, PS-341

  • DrugDexamethesone

    Administration, pre-medications and supportive care per protocol

    Also known as: Decadron

06

What researchers measure

Primary outcomes

  1. Dose-limiting Toxicities (DLT) by Age-Frailty Group [Phase Ib]

    DLT is defined as any adverse event (AE) that (a) is at least possibly related to study treatment, (b) occur during cycle 1, and (c) meets the following criteria: Hematologic - grade 4 neutropenia lasting \>5 days despite supportive care (G-CSF allowed), grade ≥3 febrile neutropenia, grade 3 thrombocytopenia with clinically significant bleeding, grade 4 thrombocytopenia unless clearly attributable to underlying disease, and any grade 5 AE; Non-Hematologic - any grade ≥3 AE (except alopecia), uncontrolled nausea, vomiting, or diarrhea not resolving to ≤ grade 1 with medical management, due to toxicity interruption of \>4 doses of iberdomide or \>1 dose of isatuximab or bortezomib (infusion-related reactions excluded), due to toxicity inability to initiate cycle 2 day 1 within 7 days.

    Time frame: Assessed continuously during induction cycle 1, up to day 28 + 30 days

  2. Recommended Phase II Dose (RP2D) of Iberdomide by Age-Frailty Group [Phase Ib]

    The RP2D of iberdomide in combination with fixed doses of isatuximab, bortezomib and dexamethasone is determined by the number of participants experiencing DLT. There are two potential iberdomide dose levels under evaluation including one de-escalation dose. The RP2D is defined as the highest dose at which fewer than 2 of 6 patients experience a DLT.

    Time frame: Assessed continuously during induction cycle 1, up to day 28 + 30 days

  3. Complete Response (CR) or Better Rate by Age-Frailty Group [Phase II]

    CR or better rate is defined as the proportion of participants who achieve a complete response (CR) or stringent CR (sCR) during induction therapy, according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC).

    Time frame: Assessed on day 1 of each cycle over 8 induction cycles (cycle duration=4 weeks), up to 32 weeks.

Secondary outcomes

  1. Induction Grade 3 or 4 Treatment-Related Adverse Event (TRAE) Rate by Age-Frailty Group [Phase Ib]

    Induction grade 3 or 4 TRAE rate is defined as the proportion of participants who experience a grade 3 or 4 AE based on Common Toxicity Criteria for Adverse Events version 5 (CTCAEv5) with a treatment attribution of possible, probable or definite during induction.

    Time frame: Assessed continuously during induction cycles 1-8 (cycle duration=4 weeks), up to 32 weeks + 30 days.

  2. Induction Best Response by Age-Frailty Group [Phase II]

    Best response over induction will be assessed according to the IMWG-URC including sCR, CR, VGPR, PR, MR, SD or PD.

    Time frame: Assessed day 1 of each cycle during induction cycles 1-8 (cycle duration=4 weeks), up to 32 weeks.

  3. Maintenance Best Response by Age-Frailty Risk Group [Phase II]

    Best response over maintenance will be assessed according to the IMWG-URC including sCR, CR, VGPR, PR, MR, SD or PD.

    Time frame: Assessed day 1 of each cycle during maintenance cycles 1-36 (cycle duration=4 weeks), up to 144 weeks.

  4. Induction Minimal Residual Disease (MRD) Negativity Rate by Age-Frailty Group [Phase II]

    Induction MRD-negative rate is defined as the proportion of participants achieving MRD negativity, as assessed by next-generation sequencing (NGS) or next-generation flow cytometry (NGF) with sensitivity of \>1 in 10-5 nucleated cells, according to the IMWG-URC.

    Time frame: Assessed after induction cycle 8 (cycle duration=4 weeks), at 32 weeks.

  5. Induction Feasibility Rate by Age-Frailty Group [Phase II]

    Induction feasibility rate is defined as the proportion of participants completing 8 cycles of induction and receiving at least one dose of maintenance treatment.

    Time frame: Assessed after induction cycle 8 (cycle duration=4 weeks), at 32 weeks plus 30 days.

  6. Induction Grade 3 or 4 TRAE Rate by Age-Frailty Group [Phase II]

    Induction grade 3 or 4 TRAE rate is defined as the proportion of participants who experience a grade 3 or 4 AE based on CTCAEv5 with a treatment attribution of possible, probable or definite during induction.

    Time frame: Assessed continuously during induction cycles 1-8 (cycle duration=4 weeks), up to 32 weeks + 30 days.

  7. Maintenance Grade 3 or 4 TRAE Rate by Age-Frailty Risk Group [Phase II]

    Maintenance grade 3 or 4 TRAE rate is defined as the proportion of participants who experience a grade 3 or 4 AE based on CTCAEv5 with a treatment attribution of possible, probable or definite during maintenance.

    Time frame: Assessed continuously during maintenance cycles 1-36 (cycle duration=4 weeks), up to 144 weeks + 30 days.

  8. Induction Serious Adverse Event (SAE) Rate by Age-Frailty Group [Phase II]

    Induction SAE is any untoward medical occurrence at any dose during induction that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization (excluding planned hospitalizations), results in persistent or significant disability or incapacity (namely a substantial disruption of normal life functions), is a congenital anomaly or birth defect, or is considered a medically important event.

    Time frame: Assessed continuously during induction cycles 1-8 (cycle duration=4 weeks), up to 32 weeks + 30 days.

  9. Maintenance SAE Rate by Age-Frailty Risk Group [Phase II]

    Maintenance SAE is any untoward medical occurrence at any dose during maintenance that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization (excluding planned hospitalizations), results in persistent or significant disability or incapacity (namely a substantial disruption of normal life functions), is a congenital anomaly or birth defect, or is considered a medically important event.

    Time frame: Assessed continuously during maintenance cycles 1-36 (cycle duration=4 weeks), up to 144 weeks + 30 days.

07

Study locations

2 sites
  • Beth Israel Deaconess Medical Center (BIDMC)
    Boston, Massachusetts 02215, United States
  • Dana-Farber Cancer Institute
    Boston, Massachusetts 02215, United States
08

References and documents

Publications

  • Avet-Loiseau H, Davies FE, Samur MK, Corre J, D'Agostino M, Kaiser MF, Raab MS, Weinhold N, Gutierrez NC, Paiva B, Neri P, Weisel K, Maura F, Walker BA, Bustoros M, Stewart AK, Usmani SZ, Hillengass J, Chng WJ, Keats JJ, Martinez-Lopez J, Sperling AS, Touzeau C, Zhan F, Raje NS, Cavo M, Bolli N, Ghobrial IM, Dhodapkar MV, Jagannath S, Spencer A, Parekh S, Bahlis NJ, Lonial S, Sonneveld P, Bergsagel L, Orlowski RZ, Morgan G, Mateos MV, Rajkumar SV, San Miguel JF, Anderson KC, Moreau P, Kumar S, Prosper F, Munshi NC. International Myeloma Society/International Myeloma Working Group Consensus Recommendations on the Definition of High-Risk Multiple Myeloma. J Clin Oncol. 2025 Aug 20;43(24):2739-2751. doi: 10.1200/JCO-24-01893. Epub 2025 Jun 9. PubMed 40489728 ↗
  • Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, Offidani M, McCarthy P, Evangelista A, Lonial S, Zweegman S, Musto P, Terpos E, Belch A, Hajek R, Ludwig H, Stewart AK, Moreau P, Anderson K, Einsele H, Durie BG, Dimopoulos MA, Landgren O, San Miguel JF, Richardson P, Sonneveld P, Rajkumar SV. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015 Mar 26;125(13):2068-74. doi: 10.1182/blood-2014-12-615187. Epub 2015 Jan 27. PubMed 25628469 ↗
  • Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, Munshi N, Lonial S, Blade J, Mateos MV, Dimopoulos M, Kastritis E, Boccadoro M, Orlowski R, Goldschmidt H, Spencer A, Hou J, Chng WJ, Usmani SZ, Zamagni E, Shimizu K, Jagannath S, Johnsen HE, Terpos E, Reiman A, Kyle RA, Sonneveld P, Richardson PG, McCarthy P, Ludwig H, Chen W, Cavo M, Harousseau JL, Lentzsch S, Hillengass J, Palumbo A, Orfao A, Rajkumar SV, Miguel JS, Avet-Loiseau H. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016 Aug;17(8):e328-e346. doi: 10.1016/S1470-2045(16)30206-6. PubMed 27511158 ↗

Individual participant data

Plan to share: Yes — The Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Supporting information: Study protocol, Sap

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 3, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT07601100
Lead sponsor
Dana-Farber Cancer Institute
Responsible party
Clifton Mo, MD (Principal Investigator, Dana-Farber Cancer Institute) — Principal investigator
First posted
May 22, 2026
Start date
Sep 3, 2026 (estimated)
Primary completion
Jul 1, 2029 (estimated)
Completion
Jul 1, 2034 (estimated)
Last update
Sep 3, 2026

Study contacts

Cliford Mo, MD
Contact
Clifton_Mo@DFCI.HARVARD.EDU
617-582-7969
Clifford Mo, MD
Contact
Clifton_Mo@DFCI.HARVARD.EDU
617-582-7969
Cliford Mo, MD
principal investigator · Dana-Farber Cancer Institute

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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