Isatuximab + Carfilzomib + Pomalidomide for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: OHSU Knight Cancer Institute

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Waldenstrom macroglobulinemia, Plasma cell leukemia, 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: 16

Duration: Up to 24 months

5 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the effect of isatuximab, carfilzomib, and pomalidomide in treating patients with multiple myeloma that has come back (relapsed) or does not respond to treatment (refractory). Isatuximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as pomalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving isatuximab, carfilzomib, and pomalidomide may help treat patients with multiple myeloma.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) for some prior treatments. If you've taken a proteasome inhibitor or an immunomodulatory drug, you'll need to stop them 2 weeks before starting the trial. If you've had anti-CD38 therapy, you'll need to stop it 6 months before the trial.

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

Research shows that Carfilzomib and Pomalidomide are effective in treating multiple myeloma, especially in patients who have not responded to other treatments. Isatuximab, when combined with Carfilzomib and Pomalidomide, has been shown to improve progression-free survival (the time during and after treatment that a patient lives with the disease without it getting worse) in patients with relapsed or refractory multiple myeloma. ^{1 2 3 4 5}

Is the combination of Isatuximab, Carfilzomib, and Pomalidomide safe for humans?

The combination of Isatuximab, Carfilzomib, and Pomalidomide has been generally well tolerated in studies for multiple myeloma, with a manageable safety profile and no new safety concerns reported. However, patients receiving these treatments may experience more severe side effects compared to using fewer drugs. ^{2 3 4 6 7}

What makes the drug combination of Isatuximab, Carfilzomib, and Pomalidomide unique for treating multiple myeloma?

This drug combination is unique because it combines Isatuximab, an antibody targeting CD38 on myeloma cells, with Carfilzomib, a proteasome inhibitor, and Pomalidomide, an immunomodulatory drug, to enhance treatment effectiveness for relapsed or refractory multiple myeloma, offering a novel approach that has shown improved progression-free survival compared to other treatments. ^{2 3 4 7 8}

Research Team

Rebecca Silbermann

Principal Investigator

OHSU Knight Cancer Institute

Eligibility Criteria

Adults with relapsed or refractory multiple myeloma, who have had at least one prior therapy, can join this trial. They must have good liver and kidney function, no severe heart issues, and not be pregnant or breastfeeding. Participants should agree to use effective contraception and not have any allergies to the drugs being tested.

Inclusion Criteria

I will use effective birth control during and for 3 months after the study.

I agree to use birth control during and for 3 months after the study.

You have an abnormal level of a specific type of protein in your blood.

Exclusion Criteria

I have not received a live vaccine in the last 30 days.

I am experiencing side effects from my previous myeloma treatment.

I have had a stem cell transplant from a donor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive isatuximab, carfilzomib, and pomalidomide. Isatuximab is administered IV on days 1, 8, 15, and 22 of cycle 1, and days 1 and 15 of subsequent cycles. Carfilzomib is administered IV on days 1, 8, 15, and pomalidomide is taken orally on days 1-21. Cycles repeat every 28 days.

Up to 24 months

4 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

24 months

Every 12 weeks

Treatment Details

Interventions

• Carfilzomib
• Isatuximab
• Pomalidomide

Trial Overview The trial is testing a combination of three treatments: Isatuximab (a monoclonal antibody), Carfilzomib (an enzyme blocker), and Pomalidomide (a chemotherapy drug). It aims to see if this trio is effective in treating patients whose multiple myeloma has returned or resisted other treatments.

Participant Groups

Group I: Treatment (isatuximab, carfilzomib, pomalidomide) Experimental Treatment 3 Interventions

Patients receive isatuximab IV over 30-60 minutes on days 1, 8, 15, and 22 of cycle 1, and days 1 and 15 of subsequent cycles, carfilzomib IV over 10 to 30 minutes on days 1, 8, 15, and pomalidomide PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Carfilzomib is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Kyprolis for:

• Multiple myeloma

Approved in European Union as Kyprolis for:

• Multiple myeloma

Approved in Canada as Kyprolis for:

• Multiple myeloma

Approved in Japan as Kyprolis for:

• Multiple myeloma

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Sanofi

Industry Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Findings from Research

Carfilzomib (CFZ) is an effective second-generation proteasome inhibitor approved for treating relapsed and refractory multiple myeloma, showing promising results even in patients with renal insufficiency and no significant impact from cytogenetic abnormalities.

Pomalidomide (POM) is a novel immunomodulatory drug with strong anti-myeloma effects, approved for patients who have not responded to previous therapies, and it has demonstrated high efficacy in those with high-risk cytogenetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New drugs in multiple myeloma - role of carfilzomib and pomalidomide. Jurczyszyn, A., Legieć, W., Helbig, G., 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]

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]

The introduction of carfilzomib, a new proteasome inhibitor, and pomalidomide, an immunomodulatory drug, has significantly improved the effectiveness of multiple myeloma treatment.

Updated NCCN Clinical Practice Guidelines now recommend the use of these drugs, indicating a positive shift in treatment options as new therapies, including monoclonal antibodies, continue to emerge.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple myeloma: new uses for available agents, excitement for the future. Anderson, KC.[2019]

Four new agents have been approved for treating relapsed/refractory multiple myeloma, including bortezomib, lenalidomide, thalidomide, and liposomal doxorubicin, but there is no standard treatment, making personalized therapy essential.

New agents like carfilzomib and pomalidomide are being studied for their effectiveness and side effects, highlighting the importance of understanding treatment-related adverse events in choosing the best therapy for individual patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related adverse events in patients with relapsed/refractory multiple myeloma. Vij, R.[2017]

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

The characteristics and outcomes of patients with multiple myeloma dual refractory or intolerant to bortezomib and lenalidomide in the era of carfilzomib and pomalidomide. [2021]

2. Poland pubmed.ncbi.nlm.nih.gov

New drugs in multiple myeloma - role of carfilzomib and pomalidomide. [2021]

3. England pubmed.ncbi.nlm.nih.gov

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

4. France pubmed.ncbi.nlm.nih.gov

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

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

Multiple myeloma: new uses for available agents, excitement for the future. [2019]

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

Treatment-related adverse events in patients with relapsed/refractory multiple myeloma. [2017]

7. 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]

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]