Isa-Pom-Dex for Multiple Myeloma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs to treat multiple myeloma, a type of blood cancer that has returned or didn't respond to previous treatments. The study uses isatuximab (a monoclonal antibody), pomalidomide (an immunomodulatory drug), and dexamethasone (a corticosteroid) at lower doses to assess their safety and effectiveness. Individuals whose multiple myeloma has returned or not responded after previous treatments might be suitable candidates, especially if they are at high risk for severe side effects from standard treatments. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from innovative therapies.

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.

Is there any evidence suggesting that the combination of isatuximab, pomalidomide, and dexamethasone is likely to be safe for humans?

Research shows that the combination of isatuximab, pomalidomide, and dexamethasone is generally well-tolerated by people with multiple myeloma. Studies have found that this combination can help patients live longer without their disease worsening.

Most patients do not experience severe side effects. In earlier studies, less than 1% of patients encountered serious problems like sepsis, a severe infection. While some side effects can occur, they are usually manageable and not life-threatening. This combination is already approved for treating multiple myeloma, indicating that its safety is well-understood. However, this trial is testing lower doses of pomalidomide and dexamethasone, which the FDA has not yet approved, so the safety of these lower doses is still under investigation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Researchers are excited about the Isa-Pom-Dex treatment for multiple myeloma because it combines three powerful drugs: Isatuximab, Pomalidomide, and Dexamethasone. Unlike many standard treatments, which often focus on a single pathway, this combo targets multiple aspects of the cancer cells. Isatuximab is unique as it specifically binds to a protein on myeloma cells called CD38, enhancing the immune system's ability to attack the cancer. Combining this with Pomalidomide, an immune modulator, and Dexamethasone, a steroid that reduces inflammation, provides a comprehensive approach that could improve outcomes for those who have relapsed or become resistant to other treatments. This multi-faceted attack is what sets Isa-Pom-Dex apart from existing options.

What evidence suggests that Isa-Pd might be an effective treatment for relapsed or refractory multiple myeloma?

Research has shown that the combination of isatuximab, pomalidomide, and dexamethasone (Isa-Pd) holds promise for treating relapsed or hard-to-treat multiple myeloma (RRMM). A real-world study found this combination effective, with patients experiencing improved outcomes. The FDA approved this treatment, indicating its efficacy for multiple myeloma. Specifically, this combination has been linked to longer periods without disease progression, allowing patients to live longer without their condition worsening. These findings suggest that Isa-Pd could be a valuable option for those whose multiple myeloma has returned or not responded to previous treatments. ^{2 6 7 8 9}

Who Is on the Research Team?

Eben I Lichtman, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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

My multiple myeloma has come back or stopped responding after initially improving with treatment.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11789454/

A Multicenter Real‐World Study - PMC - PubMed Central This multicenter real‐world analysis evaluated the efficacy of isatuximab, pomalidomide, and dexamethasone (IsaPd) in 51 patients with multiple ...

2. sarclisa.com sarclisa.com/previously-treated-trial-results

for adults with previously treated multiple myeloma Patients lived progression free for a median of 41.7 months with SARCLISA + Kyprolis (carfilzomib) and dexamethasone (Kd) vs 20.8 months with Kd alone.

3. sanofi.com sanofi.com/en/media-room/press-releases/2020/2020-03-02-18-51-16-1993727

FDA approves Sarclisa® (isatuximab-irfc) for patients with ... Sarclisa used in combination with pomalidomide and dexamethasone offers an important new treatment option for patients in the United States ...

4. multiplemyelomahub.com multiplemyelomahub.com/medical-information/image-study-isatuximab-plus-pomalidomide-and-dexamethasone-for-rrmm-in-the-real-world-setting

IMAGE study: Isatuximab plus pomalidomide and ... Here we present a visual abstract of a retrospective study by Decaux et al. which evaluated real-world outcomes following at least one dose ...

5. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4699/529353/Isatuximab-Pomalidomide-and-Dexamethasone-IsaPd-As

Isatuximab, Pomalidomide, and Dexamethasone (IsaPd) As ... This preliminary study investigates the real-world efficacy and safety of Isatuximab (Isa) combined with pomalidomide (P) and dexamethasone (d) ...

6. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-isatuximab-irfc-multiple-myeloma-0

FDA approves isatuximab-irfc for multiple myeloma The main efficacy outcome measure was progression-free survival (PFS) assessed by an independent committee based on central laboratory data for ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11215383/

Isatuximab-pomalidomide-dexamethasone versus ... Identifier: NCT02990338) demonstrated improved progression-free survival (PFS) and a benefit in overall survival (OS) was reported with the ...

8. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/7419/505213/Isatuximab-Plus-Pomalidomide-and-Dexamethasone-in

Isatuximab Plus Pomalidomide and Dexamethasone in ... In the IMAGE overall effectiveness population (median follow-up 14.2 months [mo]), median progression-free survival (mPFS) was 12.4 mo; overall ...

9. aetna.com aetna.com/cpb/medical/data/900_999/0969.html

Isatuximab-irfc (Sarclisa) - Medical Clinical Policy Bulletins Deaths due to treatment-related adverse events were reported for one patient (<1%) in the isatuximab-pomalidomide-dexamethasone group (sepsis) and two (1%) in ...