Isatuximab + Lenalidomide + Dexamethasone for Multiple Myeloma

(ITHACA Trial)

Recruiting at 202 trial locations

Overseen By Trial Transparency email recommended (Toll free number for US & Canada)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Sanofi

Must be taking: Lenalidomide, Dexamethasone

Must not be taking: Antivirals, Corticosteroids

Disqualifiers: HIV, Hepatitis, Cardiac disease, 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

Duration: 36 months

337 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug combination (isatuximab, lenalidomide, and dexamethasone) in patients with high-risk smoldering multiple myeloma. The treatment aims to boost the immune system to fight cancer cells and prevent the disease from getting worse. Lenalidomide helps the immune system and directly targets cancer cells.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that ongoing treatment with certain medications like corticosteroids above a specific dose is not allowed, and prior treatments for smoldering multiple myeloma or multiple myeloma are not permitted. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Isatuximab, Lenalidomide, and Dexamethasone for treating multiple myeloma?

Research shows that combining isatuximab with dexamethasone improves response rates and survival outcomes in patients with relapsed or refractory multiple myeloma. Additionally, isatuximab combined with other drugs like pomalidomide and dexamethasone has been shown to prolong progression-free survival, indicating its potential effectiveness in similar combinations. ^{1 2 3 4 5}

Is the combination of Isatuximab, Lenalidomide, and Dexamethasone safe for humans?

The combination of Isatuximab with other drugs like Dexamethasone and Lenalidomide has been generally well tolerated in studies for multiple myeloma, showing a manageable safety profile with no new safety concerns. Common side effects included infusion reactions and blood-related issues, but these were mostly mild to moderate in severity. ^{1 2 3 5 6}

What makes the drug combination of Isatuximab, Lenalidomide, and Dexamethasone unique for treating multiple myeloma?

This drug combination is unique because Isatuximab, an anti-CD38 monoclonal antibody, is used alongside Lenalidomide and Dexamethasone to enhance the immune system's ability to target and destroy multiple myeloma cells, offering a novel approach for patients who have relapsed or are resistant to other treatments. The combination has shown improved response rates and progression-free survival compared to other therapies. ^{1 2 3 5 6}

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

This trial is for people diagnosed within the last 5 years with high-risk smoldering multiple myeloma (SMM), which means they have certain levels of M-protein and bone marrow plasma cells but no severe symptoms. They should be able to perform daily activities with ease or with some limitations (ECOG Performance Status 0-2).

Inclusion Criteria

I can sign the consent form on my own.

I can take care of myself and am up and about more than half of my waking hours.

I was diagnosed with high-risk smoldering multiple myeloma within the last 5 years.

Exclusion Criteria

I have not received a live vaccine within 4 weeks before starting the study drug, except for the seasonal flu shot.

I do not have conditions that affect how my body absorbs medication.

I agree to use effective birth control during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

Treatment

Participants receive isatuximab in combination with lenalidomide and dexamethasone for 24 cycles, followed by isatuximab monotherapy for 12 cycles. Each cycle is 28 days.

36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 years

Treatment Details

Interventions

• Dexamethasone
• Isatuximab SAR650984
• Lenalidomide

Trial Overview The study tests if adding Isatuximab to Lenalidomide and Dexamethasone can prolong the time patients live without their disease getting worse, compared to just Lenalidomide and Dexamethasone. It's a Phase 3 trial where one group gets all three drugs, while another gets only two.

Participant Groups

Group I: Isatuximab, lenalidomide, and dexamethasone (ILd) Experimental Treatment 7 Interventions

Participants will receive isatuximab \[intravenous (IV) administration\] in combination with lenalidomide \[per os (PO) administration\] and dexamethasone \[IV on Day 1 of Cycle 1 for participants receiving isatuximab IV only and PO otherwise for subsequent cycles\] for 24 cycles followed by isatuximab monotherapy for 12 cycles for a total duration of 36 cycles. 1 cycle = 28 days. Participants may receive other treatments as pre-medication.

Group II: Lenalidomide and dexamethasone (Ld) Active Control 2 Interventions

Lenalidomide \[PO administration\] in combination with dexamethasone \[PO administration\] for 24 cycles. 1 cycle = 28 days

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

Approved in European Union as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases
• Immune system disorders

Approved in United States as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders
• Neoplastic diseases
• Nervous system disorders

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

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

Findings from Research

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 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]

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]

In the ICARIA-MM trial involving 307 patients with relapsed/refractory multiple myeloma, the combination of isatuximab, pomalidomide, and dexamethasone significantly improved median progression-free survival (PFS) compared to pomalidomide and dexamethasone alone, with PFS of 12.3 months versus 7.8 months for those with 2-3 prior therapies, and 9.4 months versus 4.3 months for those with more than 3 prior therapies.

The overall response rate (ORR) was also notably higher in patients receiving isatuximab-pomalidomide-dexamethasone, with rates of 59.0% in lenalidomide-refractory patients compared to 31.4% in the control group, demonstrating the efficacy of isatuximab across different refractory statuses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab plus pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma according to prior lines of treatment and refractory status: ICARIA-MM subgroup analysis. Bringhen, S., Pour, L., Vorobyev, V., et al.[2021]

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]

Isatuximab combined with carfilzomib and dexamethasone (Isa-Kd) demonstrated significantly better progression-free survival (PFS) compared to daratumumab combined with lenalidomide and dexamethasone (Dara-Rd) in patients with relapsed and/or refractory multiple myeloma, based on a matching-adjusted indirect comparison of 179 patients from the IKEMA trial and 286 patients from the POLLUX trial.

Patients receiving Isa-Kd experienced lower rates of treatment-emergent adverse events (TEAEs) compared to those on Dara-Rd, indicating a potentially safer profile for Isa-Kd in this treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect comparison of isatuximab plus carfilzomib and dexamethasone with daratumumab plus lenalidomide and dexamethasone in relapsed multiple myeloma. Richter, J., Lin, PL., Garcia-Horton, V., et al.[2023]

References

1. France pubmed.ncbi.nlm.nih.gov

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

2. United States pubmed.ncbi.nlm.nih.gov

Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Subgroup analysis of ICARIA-MM study in relapsed/refractory multiple myeloma patients with high-risk cytogenetics. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Isatuximab plus pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma according to prior lines of treatment and refractory status: ICARIA-MM subgroup analysis. [2021]

5. England 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. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect comparison of isatuximab plus carfilzomib and dexamethasone with daratumumab plus lenalidomide and dexamethasone in relapsed multiple myeloma. [2023]