A Phase 1b/2 Study of the Combination Isatuximab, Iberdomide, Bortezomib, and Dexamethasone in Newly Diagnosed Multiple Myeloma Who Are Transplant Ineligible or Not Intended for Upfront Transplant

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 (4)

• 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 bu the number of particpiants 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

• 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.

  Assessed continuously during induction cycles 1-8 (cycle duration=4 weeks), up to 32 weeks + 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, Kumar et al., Lancet Oncology 2016).

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

Secondary Outcomes (10)

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

  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 Ib]

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

• 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.

Study Arms (2)

Arm A: <70 and fit (standard-intensity schedule)

EXPERIMENTAL

Participants age \<70 and considered fit receive isatuximab, iberdomide, bortezomib, and dexamethasone with a standard-intensity bortezomib and dexamethasone schedule during induction, followed by maintenance for participants with at least partial response after induction. Induction (Cycles 1-8; 28-day cycles): Isatuximab: Days 1, 8, 15, 22 (Cycle 1 only) Iberdomide: Days 1-21 (Cycles 2-8) Bortezomib: Days 1, 8, 15, 22 Dexamethasone: 20 mg on Days 1, 2, 8, 9, 15, 16, 22, 23 Maintenance (for participants with ≥PR after Cycle 8; up to 36 cycles; 28-day cycles): Isatuximab: Days 1 and 15 Iberdomide: Days 1-21 (dose reductions per protocol as needed)

Drug: Arm A: Isatuximab, iberdomide, bortezomib, and dexamethasone with a standard-intensity bortezomib and dexamethasone schedule

Arm B: Age ≥70 and/or intermediate fit/frail (reduced-intensity schedule)

EXPERIMENTAL

Description: Participants age ≥70 and/or considered intermediate fit or frail receive the same regimen with reduced-intensity bortezomib and dexamethasone dosing/schedule during induction, followed by maintenance for participants with at least partial response after induction. Induction (Cycles 1-8; 28-day cycles): Isatuximab: Days 1, 8, 15, 22 (Cycle 1 only) Iberdomide: Days 1-21 (Cycles 2-8; dose reductions per protocol as needed) Bortezomib: Days 1, 8, 15 Dexamethasone: 12 mg on Days 1, 8, 15, 22 and 8 mg on Days 2, 9, 16, 23 Maintenance (for participants with ≥PR after Cycle 8; up to 36 cycles; 28-day cycles): Isatuximab: Days 1 and 15 Iberdomide: Days 1-21 (dose reductions per protocol as needed) Bortezomib: Days 1 and 15

Drug: Arm B: Isatuximab, iberdomide, bortezomib, and dexamethasone with a reduced-intensity bortezomib and dexamethasone schedule

Interventions

Arm A: Isatuximab, iberdomide, bortezomib, and dexamethasone with a standard-intensity bortezomib and dexamethasone schedule DRUG

Drug: Isatuximab (IV infusion), per protocol Drug: Iberdomide/CC-220 (oral capsule), per protocol Drug: Bortezomib (subcutaneous injection), per protocol Drug: Dexamethasone (oral tablet and/or IV per protocol), per protocol Premedications prior to isatuximab (per protocol): diphenhydramine, acetaminophen, H2 blocker (e.g., ranitidine per protocol), montelukast, and dexamethasone (route per protocol)

Arm A: <70 and fit (standard-intensity schedule)

Arm B: Isatuximab, iberdomide, bortezomib, and dexamethasone with a reduced-intensity bortezomib and dexamethasone schedule DRUG

Drug: Isatuximab (IV infusion), per protocol Drug: Iberdomide/CC-220 (oral capsule), per protocol Drug: Bortezomib (subcutaneous injection), per protocol Drug: Dexamethasone (oral tablet and/or IV per protocol), per protocol Premedications prior to isatuximab (per protocol): diphenhydramine, acetaminophen, H2 blocker (e.g., ranitidine per protocol), montelukast, and dexamethasone (route per protocol)

Arm B: Age ≥70 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

MeSH Terms

Conditions

Multiple Myeloma

Interventions

iberdomide; Bortezomib; Dexamethasone

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; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Yuxin Liu, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuxin Liu, MD

CONTACT

617-632-3823; 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 (Estimated): May 26, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2034
• Last Updated: May 22, 2026

Record last verified: 2026-03

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)