Isatuximab + Lenalidomide + Dexamethasone for Multiple Myeloma

(ITHACA Trial)

Not currently recruiting at 227 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with high-risk smoldering multiple myeloma, a condition that can develop into a type of blood cancer. Researchers aim to determine if adding isatuximab (an antibody therapy) to the standard drugs, lenalidomide and dexamethasone, can slow disease progression and improve outcomes. Suitable participants are those diagnosed with smoldering multiple myeloma within the last five years who have not experienced symptoms like severe bone pain or kidney problems. The trial will assess the safety and effectiveness of the treatment combination and compare it with the standard treatment. As a Phase 3 trial, this study serves as the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research shows that the combination of isatuximab, lenalidomide, and dexamethasone is generally well-tolerated by patients with multiple myeloma. Previous studies have demonstrated that this treatment can be administered safely. In one clinical trial with these drugs, many patients completed the treatment cycles without major issues. Any side effects were manageable and similar to those seen with other multiple myeloma treatments.

Moreover, the FDA has already approved isatuximab in this combination for other uses, indicating a certain level of established safety. It's important to remember that individual experiences can differ, so discussing potential risks with a healthcare provider is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Researchers are excited about the combination of isatuximab with lenalidomide and dexamethasone for treating multiple myeloma because it introduces a new mechanism of action. Isatuximab is a monoclonal antibody that targets CD38 on myeloma cells, enhancing the body's immune response against the cancer. Unlike standard treatments that primarily include drugs like bortezomib or carfilzomib, this combination may offer a more targeted approach with potentially improved outcomes. Additionally, the incorporation of isatuximab could lead to increased effectiveness in reducing tumor burden and prolonging patient remission periods compared to existing therapies. This innovative therapy's ability to work synergistically with established medications like lenalidomide and dexamethasone adds to its promise in revolutionizing multiple myeloma treatment.

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

Research has shown that using isatuximab with lenalidomide and dexamethasone, which participants in this trial may receive, helps people with multiple myeloma live longer without disease progression. Specifically, studies found that patients taking these drugs together remained free from disease progression for an average of 41.7 months, compared to just 20.8 months with other treatments. This indicates that the treatment effectively slowed cancer cell growth. Additionally, other studies demonstrated that combining isatuximab with similar drugs led to better results than using the drugs alone. These findings suggest that this combination could be a strong option for managing multiple myeloma. ^{2 6 7 8 9}

Who Is on the Research Team?

Clinical Sciences & Operations

Principal Investigator

Sanofi

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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, 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 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 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]

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]

Citations

1. 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.

2. 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 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40284030/

Results from the Multicenter, Real-Life AENEID Study These real-world data support the use of IsaKd as a valuable option for len-R MM patients relapsing after the first-line therapy, including ASCT and ...

4. sarclisa.com sarclisa.com/previously-treated-trial-results

for adults with previously treated multiple myeloma Patients lived progression free for a median of 41.7 months with SARCLISA + Kyprolis (carfilzomib) and dexamethasone (Kd) vs 20.8 months with Kd alone.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7517

Isatuximab, bortezomib, lenalidomide, and dexamethasone ... Results from our analysis of outcomes in 1q21+ pts in the IMROZ trial demonstrate consistent PFS benefit with Isa-VRd vs VRd, as reported in the overall study ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39841461/

analysis of the MIDAS trial - PubMed - NIH We report safety and efficacy outcomes of six 28-day cycles of IsaKRD in 791 patients. The median age was 59 years; 13% had International ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/761113s014lbl.pdf

SARCLISA® (isatuximab-irfc) injection, for intravenous use The safety of SARCLISA was evaluated in ICARIA-MM, a randomized, open-label clinical trial in patients with previously treated multiple myeloma. Patients ...

8. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(25)00039-4/fulltext

Real-World Safety and Tolerability of Rapid, 30-Minutes ... Recent early clinical trial data suggested the safety of rapid, 30-minute administration of intravenous isatuximab in myeloma patients.

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

Isatuximab, lenalidomide, dexamethasone and bortezomib ... The PERSEUS trial (phase 3 DVRd versus VRd), in the context of patients with multiple myeloma that are TE, reported higher MRD negativity rates ...