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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three treatments—isatuximab, carfilzomib, and pomalidomide—to evaluate their effectiveness in treating multiple myeloma that has returned or isn't responding to other treatments. Isatuximab targets cancer cells to stop their growth, while carfilzomib (also known as Kyprolis) and pomalidomide halt cancer cell growth through different mechanisms. The trial seeks participants previously treated for multiple myeloma, where the disease has returned or not responded to past treatments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the safety of using isatuximab, carfilzomib, and pomalidomide together has been studied in people with multiple myeloma, a type of blood cancer. An earlier study tested isatuximab with pomalidomide and found it generally well-tolerated, meaning most participants did not experience serious problems. However, some did encounter side effects; for instance, 7% of patients developed new cancers.

Isatuximab has FDA approval for treating multiple myeloma, indicating its safety for this condition is well-established. Carfilzomib and pomalidomide are also commonly used to treat multiple myeloma, often in combination with other medications.

While studies show these treatments can cause side effects, they are usually manageable. Anyone considering joining a clinical trial should discuss the possible risks and benefits with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of isatuximab, carfilzomib, and pomalidomide for multiple myeloma because it offers a new approach to tackling the disease. Unlike conventional treatments, which often involve separate therapies for myeloma, this combination brings together three powerful agents that work synergistically. Isatuximab, a monoclonal antibody, targets a specific protein on myeloma cells, enhancing the immune system's ability to attack the cancer. Carfilzomib is a proteasome inhibitor that disrupts cancer cell growth, while pomalidomide boosts the immune response and has anti-cancer effects. Together, these treatments have the potential to improve outcomes by attacking the cancer from multiple angles.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that the combination of isatuximab, carfilzomib, and pomalidomide, which participants in this trial will receive, effectively treats multiple myeloma, particularly when the cancer returns or resists other treatments. One study found that 53% of patients did not experience disease progression with this combination, compared to 42% with other treatments. Isatuximab targets cancer cells, carfilzomib inhibits cell growth, and pomalidomide helps shrink or slow the cancer's growth. This combination attacks the cancer in different ways, making it a promising option for patients facing challenging cases of multiple myeloma. ^{1 3 5 6 7}

Who Is on the Research Team?

Rebecca Silbermann

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

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

for adults with previously treated multiple myeloma At a median follow-up of 11.6 months, 53% (81 of 154 patients) lived progression free with SARCLISA + Pomalyst (pomalidomide) and dexamethasone (Pd) vs 42% (64 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04883242

Study Details | NCT04883242 | Isatuximab, Carfilzomib, ... Pomalidomide may help shrink or slow the growth of multiple myeloma. Anti-inflammatory drugs, such as dexamethasone lower the body's immune response and are ...

3. myeloma.org myeloma.org/sarclisa-isatuximab-irfc

Sarclisa (isatuximab-irfc) The study included 307 patients from 96 centers across 24 countries. The main efficacy outcome measure was progression-free survival (PFS) using IMWG criteria.

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/761113s014lbl.pdf

SARCLISA® (isatuximab-irfc) injection, for intravenous use In multiple myeloma patients treated with SARCLISA combined with pomalidomide and dexamethasone, a decrease in absolute counts of total NK cells (including ...

5. sarclisahcp.com sarclisahcp.com/faqs

Frequently Asked Questions - SARCLISA® (isatuximab-irfc) At a median follow-up time of 60 months, 63% of patients receiving SARCLISA + VRd remained on therapy, alive, and progression free vs 45% of patients receiving ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04883242

Study Details | NCT04883242 | Isatuximab, Carfilzomib, ... Pomalidomide may help shrink or slow the growth of multiple myeloma. Anti-inflammatory drugs, such as dexamethasone lower the body's immune response and are ...

7. sarclisahcp.com sarclisahcp.com/

SARCLISA® (isatuximab-irfc) | Official HCP Website In ICARIA-MM, at a median follow-up time of 52 months, second primary malignancies occurred in 7% of patients treated with SARCLISA, pomalidomide, and ...