Isa-Pom-Dex for Multiple Myeloma

Recruiting at 1 trial location

Overseen By Eben Lichtman

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Pomalidomide, Monoclonal antibodies

Disqualifiers: Recent anti-myeloma treatment, 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: Approximately 10 months

6 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study aims to evaluate the safety and effectiveness of the combination of isatuximab, pomalidomide, and dexamethasone (Isa-Pd) for the treatment of relapsed or refractory multiple myeloma (RRMM), which refers to multiple myeloma that has returned or has not responded to prior treatment. The study will specifically investigate the impact of administering lower-than-standard doses of pomalidomide and dexamethasone. Using lower doses of pomalidomide and dexamethasone in this setting has not been approved by the Food and Drug Administration (FDA).

Will I have to stop taking my current medications?

The trial requires that you stop any anti-myeloma treatment at least 2 weeks before starting the study. If you've had monoclonal antibody therapy, you need to wait 30 days, and for anti-CD38 monoclonal antibody therapy, you need to wait 6 months before joining the trial.

What data supports the effectiveness of the Isa-Pom-Dex drug 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 increases the depth of tumor response in patients with relapsed and refractory multiple myeloma. ^{1 2 3 4 5}

Is Isa-Pom-Dex safe for humans?

The combination of isatuximab, pomalidomide, and dexamethasone (Isa-Pom-Dex) has been generally well tolerated in clinical trials for multiple myeloma, with a manageable safety profile. Common side effects include infusion-related reactions, infections, and blood-related issues like low white blood cell counts, but no new safety concerns have been identified. ^{1 2 6 7 8}

What makes the Isa-Pom-Dex drug unique for treating multiple myeloma?

Isa-Pom-Dex combines isatuximab, pomalidomide, and dexamethasone, offering a novel approach by using isatuximab, an antibody that targets the CD38 protein on myeloma cells, enhancing the immune system's ability to fight the cancer. This combination has shown to significantly prolong the time patients live without their disease worsening compared to other treatments, making it a valuable option for those with relapsed or refractory multiple myeloma. ^{1 2 4 5 8}

Research Team

Eben I Lichtman, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with relapsed or refractory multiple myeloma (RRMM) who have previously responded to therapy but are considered high-risk for severe toxicity from intensive treatments. They must not have had certain recent treatments, including monoclonal antibodies within the last 30 days and stem cell transplantation within the last 12 weeks.

Inclusion Criteria

I responded to my last anti-CD38 treatment and haven't had it in 6 months.

I am 18 years old or older.

I am considered high risk for severe side effects from intense myeloma treatments.

Exclusion Criteria

I have not had anti-CD38 therapy in the last 6 months.

Your doctor believes that your overall health is too weak or fragile for any type of systemic treatment. This is often due to other health problems that are not related to the condition being studied.

I had a stem cell transplant using my own cells within the last 12 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive isatuximab, pomalidomide, and dexamethasone at lower-than-standard doses until disease progression or unacceptable side effects

Approximately 10 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including resolution or stabilization of adverse events

Up to 3 years

Treatment Details

Interventions

• Dexamethasone
• Isatuximab
• Pomalidomide

Trial Overview The study tests a combination of isatuximab, pomalidomide, and dexamethasone at lower-than-standard doses in elderly/frail patients with RRMM. The goal is to evaluate safety and effectiveness when standard full-dose regimens pose too high a risk due to potential severe side effects.

Participant Groups

Group I: Single Arm Experimental Treatment 3 Interventions

Subjects with relapsed or refractory multiple myeloma receiving the study treatment.

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

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 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 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 phase 1b study involving 45 patients with relapsed/refractory multiple myeloma, the combination of isatuximab, pomalidomide, and dexamethasone showed a 62% overall response rate and a median duration of response of 18.7 months, indicating significant efficacy in a heavily pretreated population.

The safety profile was manageable, with common adverse events including fatigue and infections, and the recommended dose for future studies was determined to be 10 mg/kg of isatuximab given weekly for the first four weeks and then every two weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1b study of isatuximab plus pomalidomide/dexamethasone in relapsed/refractory multiple myeloma. Mikhael, J., Richardson, P., Usmani, SZ., 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]

Isatuximab, a monoclonal antibody targeting CD38, was shown to significantly improve progression-free survival in adult patients with relapsed and refractory multiple myeloma when used in combination with pomalidomide and dexamethasone, compared to pomalidomide plus dexamethasone alone.

While treatment with isatuximab was associated with a higher incidence of treatment-related adverse events, including serious complications, the overall safety profile was deemed acceptable, leading to a positive benefit-risk ratio for its use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Isatuximab in Combination with Pomalidomide and Dexamethasone for the Treatment of Adult Patients with Relapsed and Refractory Multiple Myeloma. Delgado, J., Zienowicz, M., van Hennik, PB., et al.[2021]

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

4. 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]

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

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

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

A phase 1b study of isatuximab plus pomalidomide/dexamethasone in relapsed/refractory multiple myeloma. [2021]

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

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

8. England pubmed.ncbi.nlm.nih.gov

EMA Review of Isatuximab in Combination with Pomalidomide and Dexamethasone for the Treatment of Adult Patients with Relapsed and Refractory Multiple Myeloma. [2021]