Isatuximab + VRd for Multiple Myeloma

(IMROZ Trial)

Not currently recruiting at 339 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Sanofi

Must be taking: Bortezomib, Lenalidomide, Dexamethasone

Disqualifiers: Age < 18, Prior treatment, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding isatuximab (a monoclonal antibody) to a standard treatment combination can help people with newly diagnosed multiple myeloma (a type of blood cancer) live longer without disease progression. The trial compares two groups: one receiving the standard treatment and another receiving the same treatment plus isatuximab. It seeks participants who have multiple myeloma, have been recently diagnosed, and are not eligible for a transplant, often due to age or other health issues. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering patients a chance to contribute to advancing treatment options.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that combining isatuximab with bortezomib, lenalidomide, and dexamethasone is generally safe for patients with newly diagnosed multiple myeloma. This treatment proves more effective than some other standard options for this condition. Most side effects align with those already known for these drugs when used alone.

Adding isatuximab does not significantly increase the risk of new side effects. Earlier trials indicated that common side effects include low blood cell counts and tiredness, typical for these cancer treatments.

In summary, while side effects exist, they are manageable and expected for this type of therapy. Prospective participants should discuss these potential side effects with their healthcare provider to understand how they might be affected. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment involving isatuximab for multiple myeloma because it offers a novel approach compared to the standard VRd regimen (bortezomib, lenalidomide, and dexamethasone). Isatuximab is a monoclonal antibody that targets CD38 on myeloma cells, potentially leading to more effective immune-mediated destruction of cancer cells. Unlike traditional therapies, the addition of isatuximab might enhance the depth and duration of response by providing an extra layer of attack against the cancer. This treatment could offer patients a more robust and sustained remission, which is particularly promising in the fight against this challenging condition.

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

In this trial, participants will join different treatment arms to evaluate the effectiveness of isatuximab combined with other therapies for multiple myeloma. Research has shown that adding isatuximab to the treatment combination of bortezomib, lenalidomide, and dexamethasone (IVRd arm) helps patients with newly diagnosed multiple myeloma live longer without disease progression. Studies have found that patients receiving isatuximab with this combination achieve better outcomes compared to those who do not receive isatuximab. Specifically, progression-free survival (PFS) is significantly longer with isatuximab. This combination is effective for individuals who cannot undergo a transplant. The evidence supports isatuximab as a valuable addition to current multiple myeloma treatments. ^{1 2 3 6 7}

Who Is on the Research Team?

Clinical Sciences & Operations

Principal Investigator

Sanofi

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed multiple myeloma who can't have a transplant because they're over 65 or under 65 with other health issues. They must have measurable disease signs and agree to use contraception if necessary. It's not for those under 18, previously treated for myeloma, or with certain health conditions that could interfere.

Inclusion Criteria

I am over 65 or have health issues that prevent a bone marrow transplant for my newly diagnosed multiple myeloma.

I have been diagnosed with multiple myeloma.

I have been diagnosed with multiple myeloma.

Exclusion Criteria

My organ functions are not within the required range.

I am a male and agree to follow contraceptive advice during the study.

I am under 18 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 4 weeks

Induction Treatment

Participants receive induction treatment with 4 cycles of 6-week duration each, involving bortezomib, lenalidomide, and dexamethasone, with or without isatuximab

24 weeks

Continuous Treatment

Participants continue treatment with 4-week cycles involving lenalidomide and dexamethasone, with or without isatuximab

Variable, based on individual response

Crossover Period

Participants may crossover to receive isatuximab, lenalidomide, and dexamethasone in 4-week cycles

Variable, based on individual response

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 100 months after the first participant in

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Dexamethasone
• Isatuximab SAR650984
• Lenalidomide

Trial Overview The study tests whether adding Isatuximab (SAR650984) to the combo of Bortezomib, Lenalidomide, and Dexamethasone improves survival without cancer progression in new multiple myeloma patients ineligible for transplant compared to just the three-drug combo.

How Is the Trial Designed?

Group I: Isatuximab/Lenalidomide/Dexamethasone = IRd crossover arm Experimental Treatment 3 Interventions

4-weeks cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone

Group II: Isatuximab/Bortezomib/Lenalidomide/Dexamethasone = IVRd arm Experimental Treatment 4 Interventions

1. Induction treatment with 4x6-week cycles with intravenous (IV) isatuximab + subcutaneous (SC) bortezomib + oral lenalidomide + IV or oral dexamethasone 2. Continuous treatment with 4-week cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone

Group III: Bortezomib/Lenalidomide/Dexamethasone = VRd arm Active Control 3 Interventions

1. Induction treatment with 4x6-week cycles with SC bortezomib + oral lenalidomide + IV or oral dexamethasone 2. Continuous treatment with 4-week cycles with oral lenalidomide + IV or oral dexamethasone

Bortezomib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in United States as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Canada as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Japan as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Published Research Related to This Trial

Isatuximab, an anti-CD38 monoclonal antibody, significantly improves progression-free survival and tumor response when combined with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma, based on phase III studies.

The combination therapies involving isatuximab were generally well tolerated, maintaining health-related quality of life and showing a manageable safety profile without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab: A Review of Its Use in Multiple Myeloma. Frampton, JE.[2022]

In a study of 24 patients with relapsed/refractory multiple myeloma (RRMM) showing only biochemical progression, the combination of isatuximab and dexamethasone with methylprednisolone resulted in a 63% overall response rate and a 79% clinical benefit rate, indicating its efficacy.

The treatment was well tolerated, with only 5 instances of Grade ≥3 adverse events, primarily lymphocytopenia, and no severe complications related to respiratory infections, anemia, or thrombocytopenia, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of isatuximab in combination with steroids for the treatment of relapsed/refractory multiple myeloma patients exhibiting only biochemical progression-A single center retrospective study. Regidor, BS., Jew, S., Goldwater, MS., et al.[2023]

In a phase 2 study involving 164 patients with relapsed/refractory multiple myeloma, the combination of isatuximab and dexamethasone showed a significantly higher overall response rate (43.6%) compared to isatuximab alone (23.9%).

The addition of dexamethasone did not increase safety concerns, as the incidence of serious adverse events, including infections, was similar between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma. Dimopoulos, M., Bringhen, S., Anttila, P., et al.[2023]

Isatuximab, a CD38 monoclonal antibody, is effective for treating adults with relapsed/refractory multiple myeloma, particularly in combination with pomalidomide and dexamethasone after at least two prior therapies.

Nursing care for patients receiving isatuximab involves careful monitoring for adverse events like infusion reactions and neutropenia, which is crucial for providing effective patient education and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab: Nursing Considerations for Use in the Treatment of Multiple Myeloma. Wilmoth, J., Colson, K., Dubin, F., et al.[2022]

In a Phase 1b study involving 73 patients with newly diagnosed multiple myeloma who were ineligible for autologous stem cell transplantation, the combination of isatuximab with bortezomib-lenalidomide-dexamethasone (Isa-VRd) showed a remarkable overall response rate of 98.6%, with over half of the patients achieving a complete response.

While 79.5% of patients experienced grade ≥3 treatment-emergent adverse events, the pharmacokinetics of isatuximab remained consistent, indicating that the combination treatment does not affect its metabolism, supporting further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of isatuximab plus bortezomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma ineligible/with no immediate intent for autologous stem cell transplantation. Ocio, EM., Perrot, A., Bories, P., et al.[2023]

In the phase 3 ICARIA-MM trial, isatuximab combined with pomalidomide-dexamethasone significantly improved median progression-free survival (mPFS) in high-risk multiple myeloma patients, showing 7.5 months compared to 3.7 months with standard treatment.

Despite a higher incidence of grade ≥3 adverse events in high-risk patients receiving isatuximab (95.7% vs. 67.6% in the control group), the treatment did not lead to increased discontinuation or treatment-related mortality, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subgroup analysis of ICARIA-MM study in relapsed/refractory multiple myeloma patients with high-risk cytogenetics. Harrison, SJ., Perrot, A., Alegre, A., et al.[2021]

Citations

1. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-isatuximab-irfc-bortezomib-lenalidomide-and-dexamethasone-newly-diagnosed-multiple

FDA approves isatuximab-irfc with bortezomib ... A total of 446 patients were randomized (3:2) to receive either isatuximab-irfc with bortezomib, lenalidomide, and dexamethasone (Isa-VRd) or ...

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

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 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04653246

Study Details | NCT04653246 | Isatuximab, Lenalidomide, ... In this research study, investigators are evaluating whether isatuximab is safe and effective in participants with newly diagnosed multiple myeloma when given ...

4. sarclisa.com sarclisa.com/newly-diagnosed-trial-results

Newly Diagnosed Trial Results Trial 3: SARCLISA + Velcade®, Revlimid®, and dexamethasone (VRd) helped more patients live progression free vs VRd alone.

5. sarclisahcp.com sarclisahcp.com/imroz-efficacy

IMROZ Efficacy - SARCLISA® (isatuximab-irfc) See the IMROZ trial results and design for SARCLISA + bortezomib, lenalidomide, and dexamethasone (VRd) vs VRd alone. See Important Safety & Prescribing ...

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

Isatuximab, lenalidomide, dexamethasone and bortezomib ... The safety profile of both the IsaRd and Isa-VRd arms was consistent with the known safety profiles for DRd, and additionally, treatment ...

7. nejm.org nejm.org/doi/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 ...