Newly Diagnosed Multiple MyelomaPhase 1/2IsaIberVDNCT07601100
Isatuximab, Iberdomide, Bortezomib, Dexamethasone in Transplant Ineligible/Deferred Newly Diagnosed Myeloma
A Phase 1/2 study testing Isatuximab, Iberdomide and Bortezomib in people with Newly Diagnosed Multiple Myeloma, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Newly Diagnosed Multiple Myeloma
- What is being tested?
- Isatuximab, Iberdomide and Bortezomib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 2 sitesUnited States
- Study dates
- 3 Sep 2026to 1 Jul 2034
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites
Beth Israel Deaconess Medical Center (BIDMC)
Boston, Massachusetts, 02215
Clifford Mo, MD, 617-582-7969, Clifton_Mo@DFCI.HARVARD.EDU
David Avigan, MD
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Clifford Mo, MD, 617-582-7969, Clifton_Mo@DFCI.HARVARD.EDU
Cliford Mo, MD
About this study
Official title: 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
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.
- Conditions
- Newly Diagnosed Multiple Myeloma
- Being tested
- Isatuximab, Iberdomide, Bortezomib, Dexamethesone
- Keywords
- multiple myeloma, newly diagnosed multiple myeloma
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsatuximabDrug
Also called Sarclisa, Isatuximab-irfc
Administration, pre-medications and supportive care per protocol
IberdomideDrug
Also called CC-220
Administration, pre-medications and supportive care per protocol
BortezomibDrug
Also called Velcade, PS-341
Administration, pre-medications and supportive care per protocol
DexamethesoneDrug
Also called Decadron
Administration, pre-medications and supportive care per protocol
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: Isatuximab; Drug: Iberdomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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).
Measured: 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]
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.
Measured: 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]
Best response over induction will be assessed according to the IMWG-URC including sCR, CR, VGPR, PR, MR, SD or PD.
Measured: 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]
Best response over maintenance will be assessed according to the IMWG-URC including sCR, CR, VGPR, PR, MR, SD or PD.
Measured: 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]
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.
Measured: Assessed after induction cycle 8 (cycle duration=4 weeks), at 32 weeks.
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.
Measured: Assessed after induction cycle 8 (cycle duration=4 weeks), at 32 weeks plus 30 days.
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.
Measured: Assessed continuously during induction cycles 1-8 (cycle duration=4 weeks), up to 32 weeks + 30 days.
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.
Measured: Assessed continuously during maintenance cycles 1-36 (cycle duration=4 weeks), up to 144 weeks + 30 days.
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.
Measured: Assessed continuously during induction cycles 1-8 (cycle duration=4 weeks), up to 32 weeks + 30 days.
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.
Measured: Assessed continuously during maintenance cycles 1-36 (cycle duration=4 weeks), up to 144 weeks + 30 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2026
- Study start3 Sep 2026 (estimated)
- Primary completion1 Jul 2029 (estimated)
- Study completion1 Jul 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Newly Diagnosed Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 88 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Clifton Mo, MD, Dana-Farber Cancer Institute
- Investigators
- Cliford Mo, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07601100
- Sponsor's protocol ID
- 25-854
- Acronym
- IsaIberVD
- Status last verified
- Sep 2026
- First submitted
- 14 May 2026
- Last updated
- 3 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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.
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 40489728Palumbo 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 25628469Kumar 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
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07601100
- Acronym / sponsor ID
- IsaIberVD / 25-854
- Conditions
- Newly Diagnosed Multiple Myeloma
- Keywords
- multiple myeloma, newly diagnosed multiple myeloma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 88 participants (estimated)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Study start
- 3 Sep 2026 (estimated)
- Primary completion
- 1 Jul 2029 (estimated)
- Study completion
- 1 Jul 2034 (estimated)
- First posted
- 22 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Group A Induction: Age <70 years and Fit (standard-intensity schedule) | Experimental | Drug: Isatuximab, Drug: Iberdomide, Drug: Bortezomib, Drug: DexamethesoneParticipants <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 |
| Group B Induction: Age ≥70 years and/or Intermediate Fit/Frail (reduced-intensity schedule) | Experimental | Drug: Isatuximab, Drug: Iberdomide, Drug: Bortezomib, Drug: DexamethesoneParticipants ≥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 |
| Group A Maintenance: High-Risk, Age <70 years and Fit (3-drug schedule) | Experimental | Drug: Isatuximab, Drug: Iberdomide, Drug: BortezomibParticipants 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 |
| Group A Maintenance: Standard-Risk, Age <70 years and Fit (2-drug schedule) | Experimental | Drug: Isatuximab, Drug: IberdomideParticipants 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 |
| Group B Maintenance: High-Risk, Age ≥70 years and/or Intermediate Fit/Frail (3-drug schedule) | Experimental | Drug: Isatuximab, Drug: Iberdomide, Drug: BortezomibParticipants 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 |
| Group B Maintenance: Standard-Risk, Age ≥70 years and/or Intermediate Fit/Frail (2-drug schedule) | Experimental | Drug: Isatuximab, Drug: IberdomideParticipants 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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:
Key exclusion criteria (17 listed)
- Prior therapy for MM. Patients may have received:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IsatuximabAlso: Sarclisa, Isatuximab-irfcAdministration, pre-medications and supportive care per protocol | Drug | 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) |
| IberdomideAlso: CC-220Administration, pre-medications and supportive care per protocol | Drug | 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) |
| BortezomibAlso: Velcade, PS-341Administration, pre-medications and supportive care per protocol | Drug | 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) |
| DexamethesoneAlso: DecadronAdministration, pre-medications and supportive care per protocol | Drug | 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) |
Primary outcome
Dose-limiting Toxicities (DLT) by Age-Frailty Group [Phase Ib]
Time frame: Assessed continuously during induction cycle 1, up to day 28 + 30 days
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.
Recommended Phase II Dose (RP2D) of Iberdomide by Age-Frailty Group [Phase Ib]
Time frame: Assessed continuously during induction cycle 1, up to day 28 + 30 days
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.
Complete Response (CR) or Better Rate by Age-Frailty Group [Phase II]
Time frame: Assessed on day 1 of each cycle over 8 induction cycles (cycle duration=4 weeks), up to 32 weeks.
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).
9 secondary outcomes
Induction Grade 3 or 4 Treatment-Related Adverse Event (TRAE) Rate by Age-Frailty Group [Phase Ib]
Time frame: 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]
Time frame: 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]
Time frame: 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]
Time frame: Assessed after induction cycle 8 (cycle duration=4 weeks), at 32 weeks.
Induction Feasibility Rate by Age-Frailty Group [Phase II]
Time frame: Assessed after induction cycle 8 (cycle duration=4 weeks), at 32 weeks plus 30 days.
Induction Grade 3 or 4 TRAE Rate by Age-Frailty Group [Phase II]
Time frame: Assessed continuously during induction cycles 1-8 (cycle duration=4 weeks), up to 32 weeks + 30 days.
Maintenance Grade 3 or 4 TRAE Rate by Age-Frailty Risk Group [Phase II]
Time frame: Assessed continuously during maintenance cycles 1-36 (cycle duration=4 weeks), up to 144 weeks + 30 days.
Induction Serious Adverse Event (SAE) Rate by Age-Frailty Group [Phase II]
Time frame: Assessed continuously during induction cycles 1-8 (cycle duration=4 weeks), up to 32 weeks + 30 days.
Maintenance SAE Rate by Age-Frailty Risk Group [Phase II]
Time frame: Assessed continuously during maintenance cycles 1-36 (cycle duration=4 weeks), up to 144 weeks + 30 days.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2026.
- Background: PubMed 40489728Avet-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.
- Background: PubMed 25628469Palumbo 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.
- Background: PubMed 27511158Kumar 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.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Cliford Mo, MD principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Isatuximab, Iberdomide and Bortezomib in people with Newly Diagnosed Multiple Myeloma, run by Dana-Farber Cancer Institute at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Cliford Mo, MD (617-582-7969, Clifton_Mo@DFCI.HARVARD.EDU), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting Toxicities (DLT) by Age-Frailty Group [Phase Ib] (time frame: Assessed continuously during induction cycle 1, up to day 28 + 30 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07601100, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2026.