Isatuximab + Iberdomide + Bortezomib + Dexamethasone for Multiple Myeloma

(Isa Iber VD Trial)

Not yet recruiting at 1 trial location

Overseen By Yuxin Liu, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Anti-CD38 therapy

Disqualifiers: Prior malignancies, CNS involvement, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of four drugs—isatuximab, iberdomide, bortezomib, and dexamethasone—to evaluate their effectiveness for individuals newly diagnosed with multiple myeloma (a type of blood cancer) who cannot or choose not to undergo a transplant immediately. The study includes two groups: one follows a standard drug schedule for participants under 70 and generally well, while the other follows a reduced schedule for those over 70 or less physically fit. Individuals diagnosed with multiple myeloma who have not had a transplant may find this trial suitable. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in multiple myeloma treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that the combination of isatuximab, iberdomide, bortezomib, and dexamethasone is safe for patients. Research involving isatuximab with similar drugs demonstrated that patients generally tolerated the treatment well, with manageable side effects. "Manageable side effects" means that while some people experienced side effects, they were not severe enough to stop the treatment.

Another study examined iberdomide with other drugs and found similar results. The safety was acceptable, allowing patients to continue the treatment. This indicates that the combination of these drugs usually does not cause harmful reactions that outweigh the benefits.

These findings suggest that the treatment under study could be safely tolerated by patients, especially since it uses a combination of drugs with known safety records. However, because this trial includes different doses and combinations, individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of isatuximab, iberdomide, bortezomib, and dexamethasone for treating multiple myeloma because it brings together several powerful mechanisms. Isatuximab is an antibody that targets a specific protein on myeloma cells, potentially enhancing the immune system's ability to fight the cancer. Iberdomide is a novel immune-modulating agent, which could boost the body's natural defenses against cancer cells more effectively than current treatments. This combination aims to not only target the cancer cells directly but also enhance the immune response, offering a potentially more comprehensive approach than standard therapies like lenalidomide and dexamethasone.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

This trial will evaluate the combination of isatuximab, iberdomide, bortezomib, and dexamethasone for treating multiple myeloma. Participants in Arm A, who are under 70 and considered fit, will receive a standard-intensity schedule of these drugs. Meanwhile, participants in Arm B, who are 70 or older or considered intermediate fit/frail, will receive a reduced-intensity schedule. Research has shown that adding isatuximab to similar drug groups has helped patients live longer without their cancer worsening. When combined with other drugs, iberdomide has led to a reduction in cancer signs for many patients. This suggests that this drug combination could work well for people who cannot have a transplant. Early research also indicates that these treatments are generally safe, making them suitable for more frail patients. ^{1 2 5 6 7}

Who Is on the Research Team?

Yuxin Liu, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed multiple myeloma who cannot have, or are not planning to have, a stem cell transplant as their first treatment.

Inclusion Criteria

Individuals of childbearing potential must have 2 negative pregnancy tests before therapy initiation and agree to ongoing testing per Pregnancy Prevention Plan

Sexually active individuals of childbearing potential must use protocol-specified contraceptive methods starting at least 28 days prior to study drug, during treatment, interruptions, and for specified durations after last dose according to PPP

I understand the study and am willing to sign a consent form.

Exclusion Criteria

I have moderate to severe nerve pain or numbness.

History of allergic reactions to compounds chemically or biologically similar to study agents

I do not have active amyloidosis or plasma cell leukemia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction

Participants receive isatuximab, iberdomide, bortezomib, and dexamethasone over 8 cycles of 28 days each

32 weeks

Weekly visits during each cycle

Maintenance

Participants with at least partial response continue with maintenance therapy for up to 36 cycles

144 weeks

Bi-weekly visits during each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Dexamethasone
• Iberdomide
• Isatuximab

Trial Overview

The study is testing a combination of four drugs—isatuximab, iberdomide, bortezomib, and dexamethasone. Two groups will get the same drugs but at different doses and schedules for bortezomib and dexamethasone.

How Is the Trial Designed?

Group I: Arm B: Age ≥70 and/or intermediate fit/frail (reduced-intensity schedule) Experimental Treatment 1 Intervention

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

Group II: Arm A: <70 and fit (standard-intensity schedule) Experimental Treatment 1 Intervention

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)

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38832972/

Isatuximab, Bortezomib, Lenalidomide, and ...

At a median follow-up of 59.7 months, the estimated progression-free survival at 60 months was 63.2% in the isatuximab-VRd group, as compared ...

2.

onclive.com

onclive.com/view/iberdomide-daratumumab-dexamethasone-is-effective-in-newly-diagnosed-multiple-myeloma

Iberdomide/Daratumumab/Dexamethasone Is Effective in ...

The iberdomide-daratumumab-dexamethasone regimen achieved a 93.1% overall response rate in frail, transplant-ineligible multiple myeloma ...

3.

nature.com

nature.com/articles/s41591-024-03050-2

Isatuximab, lenalidomide, dexamethasone and bortezomib ...

Isa-VRd significantly increased MRD endpoints, including the 18-month negativity rate at 10 −5 , the primary endpoint, compared with IsaRd.

4.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2400712

Isatuximab, Bortezomib, Lenalidomide, and ...

Isatuximab-VRd was more effective than VRd as initial therapy in patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05272826

NCT05272826 | Study of Iberdomide, Bortezomib, ...

This study will evaluate efficacy and tolerability of iberdomide, bortezomib, dexamethasone and isatuximab on demand administered in combination.

6.

jons-online.com

jons-online.com/web-exclusives/isatuximab-bortezomib-lenalidomide-and-dexamethasone-for-transplant-ineligible-multiple-myeloma

Isatuximab, Bortezomib, Lenalidomide, and ...

The findings from a phase 1b study investigating the combination of isatuximab with VRd (Isa-VRd) demonstrated a favorable safety profile, ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12606759/

Efficacy and Safety of Isatuximab Combination Therapy in ...

The analysis of response rates revealed that isatuximab-based therapy was associated with improved depth of response across multiple endpoints.