Triple Therapy for Multiple Myeloma

(EMAT Trial)

Overseen By Medical College of Wisconsin Cancer Center Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical College of Wisconsin

Must not be taking: Chemotherapy, Immunotherapy

Disqualifiers: HIV, Hepatitis, Heart failure, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

31 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This clinical trial tests a combination of three treatments—dexamethasone (a corticosteroid), isatuximab (an antibody therapy), and lenalidomide (an immunomodulatory drug)—to determine their effectiveness for patients with multiple myeloma, a type of blood cancer, who still show minimal residual disease (small amounts of cancer cells) in their bone marrow after a stem cell transplant. The goal is to assess whether this triple therapy can better treat these patients. This trial is suitable for those diagnosed with multiple myeloma who have undergone a stem cell transplant but still have cancer cells present. Participants will receive treatment on an outpatient basis, so they won't need to stay in the hospital. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take other treatments for multiple myeloma during the study, except for local radiation therapy. You may continue corticosteroids if they are for conditions other than multiple myeloma.

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

Research has shown that the combination of isatuximab, lenalidomide, and dexamethasone is generally well-tolerated for treating multiple myeloma. One study found that the safety of this combination was similar to other treatments. Common side effects included tiredness and nausea, but most patients managed these well.

However, some risks exist. Isatuximab can cause serious infections, so healthcare providers must monitor for any signs of infection during treatment. Despite these risks, the overall safety data for this treatment indicates it is manageable with proper medical care. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the triple therapy of isatuximab, lenalidomide, and dexamethasone for multiple myeloma because it introduces a novel combination approach that may enhance treatment efficacy. Isatuximab, a monoclonal antibody, specifically targets and binds to a protein on cancer cells called CD38, which is different from traditional therapies that may not target this protein as precisely. This targeted action can potentially lead to better outcomes by directly attacking the cancer cells while minimizing harm to normal cells. Additionally, when combined with lenalidomide and dexamethasone, which have already shown effectiveness in treating multiple myeloma, the synergy of this trio could offer improved results over current standard treatments.

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

Research has shown that a combination of isatuximab, lenalidomide, and dexamethasone may effectively treat multiple myeloma. In this trial, participants will receive this combination therapy, known as IsaRD, on an outpatient basis. Studies found that adding isatuximab to this treatment plan helped patients live longer without their disease worsening. Specifically, patients who received isatuximab along with lenalidomide and dexamethasone had better results than those who did not receive isatuximab. These findings suggest that this combination could be a promising treatment for multiple myeloma. ^{6 7 8 9 10}

Who Is on the Research Team?

Meera Mohan, MD

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

This trial is for adults over 18 with multiple myeloma who still have cancer cells in their bone marrow after a stem cell transplant. They must be able to give consent, not be pregnant or breastfeeding, and can't join if they've had recent major surgery, active infections, other cancers needing treatment, severe heart conditions, known allergies to study drugs or certain components of them.

Inclusion Criteria

My bone marrow test shows cancer cells after a stem cell transplant.

Your absolute neutrophil count is at least 1,000 per cubic millimeter.

I have been diagnosed with symptomatic multiple myeloma, and I may have amyloidosis but won't receive treatment for it during the study.

Exclusion Criteria

Pregnant or breastfeeding subjects

I am not planning to receive any cancer treatment other than what this study offers from Day +30 post-transplant, except for local radiation or steroids for non-cancer conditions.

I haven't needed antibiotics for an infection in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination of isatuximab, lenalidomide, and dexamethasone (IsaRD) for 12 28-day cycles

12 months

Monthly visits (outpatient)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone
• Isatuximab
• Lenalidomide

Trial Overview The study tests Dexamethasone, Lenalidomide, and Isatuximab on patients with minimal residual disease post-transplant. It's a phase II trial at one center where all participants receive the same treatment without comparison groups.

How Is the Trial Designed?

Group I: Isatuximab in combination with lenalidomide and dexamethasone. Experimental Treatment 3 Interventions

The isatuximab, lenalidomide, and dexamethasone (IsaRD) therapy will be administered on an outpatient basis.

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?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

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]

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]

Daratumumab, when combined with lenalidomide and dexamethasone (DRd) or bortezomib and dexamethasone (DVd), showed an overall response rate of 80% in 171 heavily treated patients with relapsed/refractory multiple myeloma, indicating its efficacy in this challenging patient population.

Patients receiving the DRd combination experienced better progression-free survival (PFS) compared to those on DVd, with PFS rates of 84% and 77%, respectively, while the treatment was generally safe, with common side effects including neutropenia and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab combined with dexamethasone and lenalidomide or bortezomib in relapsed/refractory multiple myeloma (RRMM) patients: Report from the multiple myeloma GIMEMA Lazio group. Fazio, F., Franceschini, L., Tomarchio, V., et al.[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 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 phase 1b study involving 57 patients with relapsed/refractory multiple myeloma, the combination of isatuximab, lenalidomide, and dexamethasone was found to be generally well tolerated, with only one dose-limiting toxicity reported, indicating a favorable safety profile.

The treatment demonstrated an overall response rate of 56% and a median progression-free survival of 8.5 months, suggesting that isatuximab is an effective option for patients who have previously undergone multiple treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma. Martin, T., Baz, R., Benson, DM., 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 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]

Citations

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

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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 ...

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Isatuximab, bortezomib, lenalidomide, and dexamethasone ... Phase 3 study results of isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) versus VRd for transplant-ineligible patients with ...

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

analysis of the MIDAS trial - PubMed - NIH Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone Induction in Newly Diagnosed Myeloma: Analysis of the MIDAS Trial

7. sarclisa.com sarclisa.com/possible-side-effects

SARCLISA® (isatuximab-irfc) | Possible Side Effects SARCLISA can cause infections that are severe, life-threatening, or that may lead to death. Your healthcare provider will monitor you for signs and symptoms of ...

8. 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 ...

9. 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 ... Introduction. The treatment with anti-CD 38 antibodies significantly improved the outcome of patients with multiple myeloma. The anti-CD 38 antibody Isatuximab ...

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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 ...