Isatuximab + Pomalidomide + Dexamethasone for Multiple Myeloma

(IRAKLIA Trial)

Not currently recruiting at 308 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of isatuximab (an antibody therapy) when administered either subcutaneously or intravenously, alongside two other drugs, for individuals with multiple myeloma. Multiple myeloma is a type of blood cancer, and this trial targets those who have previously tried at least one other treatment that included lenalidomide and a proteasome inhibitor. Participants will receive isatuximab with pomalidomide and dexamethasone to determine which administration method is more effective or easier to manage. Individuals with measurable signs of multiple myeloma who have undergone specific past treatments may qualify for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants access to potentially effective treatment options.

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.

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

Research has shown that isatuximab, administered either intravenously (IV) or subcutaneously (SC), is generally well-tolerated by patients with multiple myeloma. Studies found that the IV method was well-tolerated, with no patients needing to slow the infusion rate. Another study showed that combining isatuximab with other treatments did not introduce new safety issues, though there was a 7% increased risk of low blood platelet count (thrombocytopenia).

For the SC method, research indicates it is as safe as the IV method. The FDA approved the SC method based on a study that demonstrated its effectiveness and safety. This suggests that both IV and SC methods are safe to use, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for multiple myeloma, which often involve traditional chemotherapy and immunomodulatory drugs like lenalidomide and bortezomib, Isatuximab offers a fresh approach by targeting a specific protein on cancer cells called CD38. This precision targeting potentially reduces damage to healthy cells, enhancing the drug's effectiveness. Furthermore, researchers are excited about the new subcutaneous administration method of Isatuximab, which could offer greater convenience and comfort compared to the conventional intravenous method. This delivery method might make it easier for patients to receive treatment and improve their overall quality of life.

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

Studies have shown that isatuximab, when combined with medications like pomalidomide and dexamethasone, effectively treats multiple myeloma. In this trial, participants will receive either intravenous (IV) or subcutaneous (SC) isatuximab. For IV use, isatuximab has helped patients live longer without disease progression. One study found that patients receiving isatuximab with standard treatment had a better complete response, with no signs of multiple myeloma detected. SC isatuximab also shows promise, with 79.7% of patients experiencing tumor reduction or disappearance. Both IV and SC methods are well tolerated, making them suitable options for treatment in this trial. ^{2 3 4 5 6}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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 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 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]

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]

Citations

1. myeloma.org myeloma.org/sarclisa-isatuximab-irfc

Sarclisa (isatuximab-irfc) The study included 307 patients from 96 centers across 24 countries. The main efficacy outcome measure was progression-free survival (PFS) using IMWG criteria.

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

Newly Diagnosed Trial Results Trial 3 also measured complete response or better, which means that a patient's multiple myeloma improved with treatment to the point where there are no signs ...

3. sarclisahcp.com sarclisahcp.com/imroz-efficacy

IMROZ Efficacy - SARCLISA® (isatuximab-irfc) At a median follow-up time of 60 months, 26% of patients in the SARCLISA + VRd group and 32.6% of patients in the VRd group had died; HR=0.78 (95% CI: 0.55, 1.1) ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2152265025000394

Real-World Safety and Tolerability of Rapid, 30-Minutes ... The rapid 30-minutes intravenous isatuximab was adequately tolerated in all patients. No patient was changed back to the standard administration rate.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8497289/

Isatuximab: A Review of Its Use in Multiple Myeloma - PMC Isatuximab-based combination therapies were generally well tolerated and demonstrated a manageable safety profile with no new safety signals. Although mature ...

6. nature.com nature.com/articles/s41598-024-83014-1

Comprehensive safety evaluation of isatuximab in multiple ... The results demonstrated a 7% increased risk of thrombocytopenia (RR = 1.07, 95% CI: 1.01–1.14, p = 0.0213) (Fig. 3a) in the isatuximab therapy.