Isa-Rd Combo Therapy for Multiple Myeloma

Recruiting at 4 trial locations

Overseen By Lori Stravers

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Corticosteroids, Antibiotics, others

Disqualifiers: Infection, Heart failure, Amyloidosis, 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: Up to 2 years

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is investigating the safety and effectiveness of using combination of isatuximab, lenalidomide and dexamethasone for the treatment of newly diagnosed multiple myeloma (MM). The study team will use lower doses than is currently standard for these drugs. Lower doses will be used to avoid or possibly reduce any unwanted side effects commonly associated with these drugs. Using lower doses of the combination isatuximab, lenalidomide and dexamethasone, has not been approved by the Food and Drug Administration (FDA) for the treatment of newly diagnosed MM.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on medications that are prohibited by the study, you may need to discontinue or replace them with alternatives.

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

Research shows that adding Isatuximab to Dexamethasone improves response rates and survival outcomes in patients with relapsed or refractory multiple myeloma. Additionally, Isatuximab combined with other drugs like pomalidomide has been shown to prolong progression-free survival, indicating its potential effectiveness in similar combinations. ^{1 2 3 4 5}

Is Isa-Rd Combo Therapy for Multiple Myeloma safe for humans?

The Isa-Rd Combo Therapy, which includes isatuximab, lenalidomide, and dexamethasone, has been generally well tolerated in clinical trials for multiple myeloma, with a manageable safety profile and no new safety concerns. Common side effects include infusion reactions and blood-related issues, but serious infections were similar to other treatments. ^{1 2 5 6 7}

What makes the Isa-Rd Combo Therapy for Multiple Myeloma unique?

The Isa-Rd Combo Therapy is unique because it combines isatuximab, a monoclonal antibody targeting CD38, with lenalidomide and dexamethasone, which enhances the immune system's ability to fight multiple myeloma. This combination has shown improved response rates and survival outcomes compared to isatuximab alone, offering a novel approach for patients who have relapsed or are resistant to other treatments. ^{1 2 3 6 7}

Research Team

Sascha Tuchman, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria

This trial is for older or frail patients with newly diagnosed multiple myeloma who haven't had more than 28 days of anti-myeloma therapy. They must be at high risk for severe side effects from standard treatments, have measurable MM and related organ dysfunction, and show adequate organ function. Women of childbearing age must use birth control.

Inclusion Criteria

Willing and able to adhere to the study visit schedule and other protocol requirements based on the judgement of the investigator or protocol designee.

Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information (PHI).

My organ functions and lab tests meet the required standards.

Exclusion Criteria

I have not had a serious infection or needed antibiotics in the last 14 days.

Receiving other investigational agents less than 14 days or 5 half-lives of first dose of therapy on this protocol, whichever is longer.

I have a stomach or bowel condition that affects how I absorb pills or tolerate certain medications.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive isatuximab, lenalidomide, and dexamethasone with 28-day cycles. Isatuximab is administered for two years, dexamethasone weekly for the first eight cycles, and lenalidomide continued as maintenance until disease progression or unacceptable toxicity.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment until death or full withdrawal from the study. Those withdrawn for adverse events are followed for resolution or stabilization of the adverse event(s).

Until death or full withdrawal

Treatment Details

Interventions

• Dexamethasone
• Isatuximab
• Lenalidomide

Trial Overview The study tests a combination of isatuximab, lenalidomide, and dexamethasone at lower doses than usual to see if it's safe and effective for treating new multiple myeloma cases while minimizing side effects. This approach isn't FDA-approved yet.

Participant Groups

Group I: Single Arm Experimental Treatment 3 Interventions

All subjects will receive the same treatment on the study, consisting of isatuximab, lenalidomide, and dexamethasone with 28 days cycles.

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?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

Genzyme, a Sanofi Company

Industry Sponsor

Trials

528

Recruited

186,000+

David Meeker

Genzyme, a Sanofi Company

Chief Executive Officer since 2011

MD from the University of Vermont Medical School, Advanced Management Program at Harvard Business School

Jean-Paul Kress

Genzyme, a Sanofi Company

Chief Medical Officer since 2015

MD from Faculte Necker-Enfants Malades, Paris

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 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 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 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]

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]

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 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]

4. 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]

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

Subgroup analysis of ICARIA-MM study in relapsed/refractory multiple myeloma patients with high-risk cytogenetics. [2021]

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

Matching-adjusted indirect comparison of isatuximab plus carfilzomib and dexamethasone with daratumumab plus lenalidomide and dexamethasone in relapsed multiple myeloma. [2023]