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

Trial Summary

What is the purpose of this trial?

This is a single-center, single-arm, phase II study that will enroll multiple myeloma (MM) patients with persistent bone marrow minimal residual disease (MRD) post autologous stem cell transplant (ASCT) irrespective of the International Myeloma Working Group (IMWG) response.

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.

What data supports the effectiveness of the drug combination of Dexamethasone, Isatuximab, and Lenalidomide 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 significantly prolong progression-free survival, indicating its potential effectiveness in similar drug combinations. ^{1 2 3 4 5}

Is the triple therapy for multiple myeloma safe for humans?

The triple therapy involving isatuximab, lenalidomide, and dexamethasone has been generally well tolerated in clinical studies for multiple myeloma, with manageable side effects and no new safety concerns. Common side effects included infusion-related reactions, which were mostly mild, and some patients experienced more severe side effects like pneumonia. ^{2 4 6 7 8}

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

This triple drug therapy is unique because it combines isatuximab, an anti-CD38 monoclonal antibody, with lenalidomide and dexamethasone, which together enhance the immune system's ability to target and destroy multiple myeloma cells, offering improved progression-free survival and response rates compared to other treatments. ^{1 2 3 5 9}

Research Team

Meera Mohan, MD

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

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

I am 18 years old or older.

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

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

Exclusion Criteria

Pregnant or breastfeeding subjects

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

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.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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

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

2. France pubmed.ncbi.nlm.nih.gov

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

3. 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]

4. 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]

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. 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]

7. United States 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. [2022]

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

A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma. [2021]

9. England pubmed.ncbi.nlm.nih.gov

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