Isatuximab + Pomalidomide + Dexamethasone for Multiple Myeloma

(IRAKLIA Trial)

Recruiting at 278 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Sanofi

Must be taking: Lenalidomide, Proteasome inhibitors

Must not be taking: Anti-CD38, Pomalidomide

Disqualifiers: Cardiac dysfunction, Other malignancy, HIV, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Up to approximately 4 years

531 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of three drugs to treat patients with multiple myeloma whose disease has not responded to previous treatments. The drugs include isatuximab, which can be given as an injection or through a vein, along with pomalidomide and dexamethasone. The treatment works by helping the immune system fight cancer and directly attacking cancer cells. Isatuximab is approved for use in combination with pomalidomide and dexamethasone for treating multiple myeloma.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does exclude those who have had certain treatments recently, like anti-CD38 treatment within 9 months or prior therapy with pomalidomide.

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

Research shows that adding Isatuximab to Pomalidomide and Dexamethasone significantly improves progression-free survival (the time during and after treatment that a patient lives with the disease without it getting worse) and enhances the depth of tumor response in patients with relapsed and refractory multiple myeloma. ^{1 2 3 4 5}

Is the combination of Isatuximab, Pomalidomide, and Dexamethasone safe for treating multiple myeloma?

The combination of Isatuximab, Pomalidomide, and Dexamethasone is generally well tolerated and has a manageable safety profile, with no new safety concerns reported. However, some patients may experience serious side effects like low white blood cell counts (neutropenia), infections, and low platelet counts (thrombocytopenia). ^{1 2 3 6 7}

What makes the drug Isatuximab unique for treating multiple myeloma?

Isatuximab is unique because it is a monoclonal antibody that targets the CD38 receptor on myeloma cells, enhancing the effectiveness of other drugs like pomalidomide and dexamethasone. This combination has shown to significantly improve progression-free survival in patients with relapsed and refractory multiple myeloma compared to using pomalidomide and dexamethasone alone. ^{1 2 4 5 7}

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

This trial is for adults with multiple myeloma who've had at least one prior treatment including lenalidomide and a proteasome inhibitor. They must have measurable levels of certain proteins in their blood or urine, be able to perform daily activities (ECOG ≤2), and agree to use effective birth control. Excluded are those under 18, with severe heart issues, specific other cancers or conditions, or who don't meet safety lab criteria.

Inclusion Criteria

You have high levels of certain proteins in your blood or urine.

I have multiple myeloma and have been treated with lenalidomide and a proteasome inhibitor.

Exclusion Criteria

I have been treated with pomalidomide before.

I have HIV/AIDS and need antiviral treatment.

I am under 18 years old.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Isatuximab in combination with Pomalidomide and Dexamethasone in 4-week cycles until disease progression or other criteria are met

Up to approximately 4 years

Weekly visits during Cycle 1, bi-weekly visits in subsequent cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Isatuximab

Trial Overview The study compares two ways of giving Isatuximab (either through the skin as SC or into a vein as IV) combined with Pomalidomide and Dexamethasone in patients whose multiple myeloma has returned after treatment. Participants will be randomly assigned to one of these methods and can continue until their disease worsens or they experience unacceptable side effects.

Participant Groups

Group I: Isatuximab Subcutaneous (SC) Experimental Treatment 7 Interventions

Isatuximab dose will be administered SC weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days in duration. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days). Participants may receive other treatments as background treatment and/or rescue medication.

Group II: Isatuximab Intravenous (IV) Active Control 7 Interventions

Isatuximab dose will be administered via IV infusion weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days). Participants may receive other treatments as background treatment and/or rescue medication.

Isatuximab is already approved in European Union, United States for the following indications:

Approved in European Union as Sarclisa for:

• Multiple myeloma

Approved in United States as Sarclisa for:

• Multiple myeloma in combination with pomalidomide and dexamethasone for adults who have received at least two prior therapies including lenalidomide and a proteasome inhibitor
• Multiple myeloma in combination with carfilzomib and dexamethasone for adults with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
• Newly diagnosed multiple myeloma in combination with bortezomib, lenalidomide, and dexamethasone for adults who are not eligible for autologous stem cell transplant

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 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 subgroup analysis of 36 East Asian patients with relapsed/refractory multiple myeloma, the combination of isatuximab, pomalidomide, and dexamethasone (Isa-Pd) showed improved progression-free survival compared to pomalidomide and dexamethasone alone, with a median progression-free survival not reached in the Isa-Pd group versus 7.9 months in the Pd group.

The safety profile of Isa-Pd in East Asian patients was consistent with the overall population, although a higher incidence of Grade ≥ 3 neutropenia was observed, indicating that while the treatment is effective, monitoring for this side effect is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab-Pomalidomide-Dexamethasone Versus Pomalidomide-Dexamethasone in East Asian Patients With Relapsed/Refractory Multiple Myeloma: ICARIA-MM Subgroup Analysis. Sunami, K., Ikeda, T., Huang, SY., et al.[2022]

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 3 study involving 307 patients with relapsed and refractory multiple myeloma, the combination of isatuximab, pomalidomide, and dexamethasone significantly improved progression-free survival (11.5 months) compared to pomalidomide and dexamethasone alone (6.5 months).

The most common side effects included infusion reactions and upper respiratory infections, with a low incidence of treatment-related deaths, indicating that isatuximab is a relatively safe and effective treatment option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Attal, M., Richardson, PG., Rajkumar, SV., et al.[2020]

In a study of 107 relapsed/refractory myeloma patients treated with isatuximab, pomalidomide, and dexamethasone (IsaPomDex), the overall response rate was 66.4%, indicating significant efficacy in a real-world setting.

The treatment was associated with a median progression-free survival of 10.9 months and a median overall survival of 18.8 months, although adverse events were common, with 87.9% of patients experiencing any grade adverse effects, primarily neutropenia and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Isatuximab With Pomalidomide and Dexamethasone in Relapsed Myeloma: Results of a UK-Wide Real-World Dataset. Djebbari, F., Rampotas, A., Vallance, G., et al.[2022]

In a phase 3 study involving 302 patients with relapsed multiple myeloma, the addition of isatuximab to carfilzomib-dexamethasone significantly improved progression-free survival compared to carfilzomib-dexamethasone alone, with a hazard ratio of 0.53, indicating a 47% reduction in the risk of disease progression.

While the isatuximab group experienced a higher rate of treatment-emergent adverse events (77% vs. 67%), the overall safety profile was similar, with no significant difference in fatal adverse events, suggesting that isatuximab can be safely integrated into treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Moreau, P., Dimopoulos, MA., Mikhael, J., et al.[2022]

References

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

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

2. 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]

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

Isatuximab-Pomalidomide-Dexamethasone Versus Pomalidomide-Dexamethasone in East Asian Patients With Relapsed/Refractory Multiple Myeloma: ICARIA-MM Subgroup Analysis. [2022]

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

Isatuximab: Nursing Considerations for Use in the Treatment of Multiple Myeloma. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. [2020]

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

Efficacy of Isatuximab With Pomalidomide and Dexamethasone in Relapsed Myeloma: Results of a UK-Wide Real-World Dataset. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. [2022]