Phase 1b/2: Isatuximab, Iberdomide, Bortezomib, Dexamethasone in Transplant Ineligible/Deferred Newly Diagnosed Myeloma

NCT07601100 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 25-854
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 2

Brief 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

Conditions

Newly Diagnosed Multiple Myeloma

Keywords

multiple myeloma; newly diagnosed multiple myeloma

Outcome Measures

Primary Outcomes (3)

• 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.

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

• 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.

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

• 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).

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

Secondary Outcomes (9)

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

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

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

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

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

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

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

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

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

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

Study Arms (6)

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

Isatuximab DRUG

Administration, pre-medications and supportive care per protocol

Also known as: Sarclisa, Isatuximab-irfc

Group A Induction: Age <70 years and Fit (standard-intensity schedule); Group A Maintenance: High-Risk, Age <70 years and Fit (3-drug schedule); Group A Maintenance: Standard-Risk, Age <70 years and Fit (2-drug schedule); Group B Induction: Age ≥70 years and/or Intermediate Fit/Frail (reduced-intensity schedule); Group B Maintenance: High-Risk, Age ≥70 years and/or Intermediate Fit/Frail (3-drug schedule); Group B Maintenance: Standard-Risk, Age ≥70 years and/or Intermediate Fit/Frail (2-drug schedule)

Iberdomide DRUG

Administration, pre-medications and supportive care per protocol

Also known as: CC-220

Group A Induction: Age <70 years and Fit (standard-intensity schedule); Group A Maintenance: High-Risk, Age <70 years and Fit (3-drug schedule); Group A Maintenance: Standard-Risk, Age <70 years and Fit (2-drug schedule); Group B Induction: Age ≥70 years and/or Intermediate Fit/Frail (reduced-intensity schedule); Group B Maintenance: High-Risk, Age ≥70 years and/or Intermediate Fit/Frail (3-drug schedule); Group B Maintenance: Standard-Risk, Age ≥70 years and/or Intermediate Fit/Frail (2-drug schedule)

Bortezomib DRUG

Administration, pre-medications and supportive care per protocol

Also known as: Velcade, PS-341

Group A Induction: Age <70 years and Fit (standard-intensity schedule); Group A Maintenance: High-Risk, Age <70 years and Fit (3-drug schedule); Group B Induction: Age ≥70 years and/or Intermediate Fit/Frail (reduced-intensity schedule); Group B Maintenance: High-Risk, Age ≥70 years and/or Intermediate Fit/Frail (3-drug schedule)

Dexamethesone DRUG

Administration, pre-medications and supportive care per protocol

Also known as: Decadron

Group A Induction: Age <70 years and Fit (standard-intensity schedule); Group B Induction: Age ≥70 years and/or Intermediate Fit/Frail (reduced-intensity schedule)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead

Study Sites (2)

Beth Israel Deaconess Medical Center (BIDMC)

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (3)

• 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.

  PMID: 40489728 BACKGROUND

• 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.

  PMID: 25628469 BACKGROUND

• 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.

  PMID: 27511158 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma

Interventions

isatuximab; iberdomide; Bortezomib; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Yuxin Liu, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuxin Liu, MD

CONTACT

857-215-3056; yuxin_liu@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 14, 2026
• First Posted: May 22, 2026
• Study Start: June 26, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2034
• Last Updated: June 1, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer office for Dana -Farber Innovations (BODFI) at innovations@dfci.harvard.edu

Locations

US (2)