Donor Immune Cells + Isatuximab for Multiple Myeloma

Overseen By Julie Zipfel

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Elvira Umyarova

Must be taking: Cyclophosphamide, Dexamethasone

Must not be taking: Corticosteroids, Alternative medicines

Disqualifiers: CNS MM, Waldenstrom, AL amyloidosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and explore side effects of a new combination treatment for multiple myeloma, a type of blood cancer, in patients whose disease has returned or not responded to previous treatments. The treatment combines special lab-made immune cells (NK cells) with a drug called isatuximab, which enhances the immune system's ability to fight cancer. Participants will also receive standard medications, cyclophosphamide and dexamethasone, commonly used in cancer treatment. This trial may suit those who have tried at least three different treatments for multiple myeloma and still find their disease resistant or recurring. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I need to stop my current medications to join the trial?

The trial requires that you stop your last treatment at least 2 weeks before starting the study. However, the protocol does not specify if you need to stop other current medications, so it's best to discuss this with the trial team.

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

Research shows that isatuximab, a treatment for multiple myeloma, is generally safe. Some studies have found a small increase in the risk of thrombocytopenia, which means having fewer platelets in the blood and can lead to easy bruising or bleeding, with a 7% higher risk reported. The FDA has approved this treatment, indicating it is considered safe for use in other conditions.

Information on Universal Donor Expanded TGF-beta-imprinted NK Cells, or TiNK cells, is still developing. These special immune cells are designed to better attack cancer cells and have been used safely with other treatments in various clinical settings.

In this trial, these treatments are used together. Previous evidence suggests that this combination might be safe and effective for treating relapsed or refractory multiple myeloma, but more data is needed to fully understand the safety in this specific use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using donor immune cells combined with isatuximab for multiple myeloma because this approach taps into the body's natural defenses in a novel way. While most treatments for multiple myeloma, like bortezomib or lenalidomide, focus on directly attacking cancer cells, this method uses specially prepared NK (natural killer) cells from donors to enhance the immune system's ability to fight the disease. The addition of isatuximab, an antibody targeting a protein on myeloma cells, potentially boosts the immune response even further. This dual-action approach could offer a more powerful and targeted attack on the cancer than standard therapies alone.

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

Research shows that isatuximab, one of the treatments in this trial, helps patients with multiple myeloma live longer without their cancer worsening when combined with other medications. In one study, 74% of patients did not experience cancer progression when isatuximab was added to their treatment. Participants in this trial will receive a combination of treatments, including isatuximab and enhanced NK cells. NK cells are special immune cells designed to attack cancer more effectively, boosting the body's natural ability to fight the disease. Early research suggests that using these enhanced NK cells with isatuximab might be a safe and promising way to treat multiple myeloma that has returned or not responded to previous treatments. ^{2 3 4 6 7}

Who Is on the Research Team?

Elvira Umyarova, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with multiple myeloma that has either returned after treatment or hasn't responded to previous therapies. Participants must meet certain health standards, which are not specified here.

Inclusion Criteria

Left ventricular ejection fraction ≥ 30%

Fertility requirements for women of child bearing potential (WOCBP) must be met

I agree to use birth control during and up to 6 months after the study.

Exclusion Criteria

Patients with known positivity for human immunodeficiency virus (HIV) or active hepatitis B/C

Any other medical condition, including mental illness or substance abuse, deemed by the investigator(s) to likely interfere with the patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results

Life expectancy of 6 months or less

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive cyclophosphamide, dexamethasone, TiNK, and isatuximab. Treatment repeats every 28 days for up to 6 cycles.

24 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs at 30 days, 60 days, and every 12 weeks for up to 2 years.

2 years

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Dexamethasone
• Isatuximab
• Universal Donor Expanded TGF-beta-imprinted NK Cells

Trial Overview

The study is testing the safety and optimal dosage of lab-enhanced NK cells (TiNK) combined with isatuximab, alongside standard treatments cyclophosphamide and dexamethasone, in treating relapsed or refractory multiple myeloma.

How Is the Trial Designed?

Group I: Treatment (cyclophosphamide, dexamethasone, TiNK, isatuximab) Experimental Treatment 8 Interventions

Patients receive cyclophosphamide IV on day 1, dexamethasone PO on days 1-4, TiNK IV on day 8, and isatuximab IV on days 8 and 15 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and biopsy during screening and on study, as well as optionally during follow up. Patients undergo ECHO during screening and blood sample collection throughout the study.

Isatuximab is already approved in European Union, United States for the following indications:

Approved in European Union as Sarclisa for:

• Multiple myeloma

Approved in United States as Sarclisa for:

• Multiple myeloma in combination with pomalidomide and dexamethasone for adults who have received at least two prior therapies including lenalidomide and a proteasome inhibitor
• Multiple myeloma in combination with carfilzomib and dexamethasone for adults with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
• Newly diagnosed multiple myeloma in combination with bortezomib, lenalidomide, and dexamethasone for adults who are not eligible for autologous stem cell transplant

Who Is Running the Clinical Trial?

Elvira Umyarova

Lead Sponsor

Trials

1

Recruited

30+

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

The phase 1 trial of IPH2101, an anti-KIR antibody, demonstrated safety and tolerability in 32 patients with relapsed/refractory multiple myeloma, achieving full KIR2D occupancy without dose-limiting toxicity.

Although no objective responses were observed, IPH2101 enhanced the cytotoxicity of patient-derived NK cells against multiple myeloma cells, indicating potential for further development in treating this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 trial of the anti-KIR antibody IPH2101 in patients with relapsed/refractory multiple myeloma. Benson, DM., Hofmeister, CC., Padmanabhan, S., et al.[2021]

In a phase 1b study involving 57 patients with relapsed/refractory multiple myeloma, the combination of isatuximab, lenalidomide, and dexamethasone was found to be generally well tolerated, with only one dose-limiting toxicity reported, indicating a favorable safety profile.

The treatment demonstrated an overall response rate of 56% and a median progression-free survival of 8.5 months, suggesting that isatuximab is an effective option for patients who have previously undergone multiple treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma. Martin, T., Baz, R., Benson, DM., et al.[2021]

In a phase 3 trial involving 660 patients with newly diagnosed multiple myeloma, the addition of isatuximab to standard treatment (lenalidomide, bortezomib, and dexamethasone) significantly improved the rate of minimal residual disease (MRD) negativity, with 50% of patients in the isatuximab group achieving MRD negativity compared to 36% in the control group.

The safety profile of isatuximab was consistent with existing treatments, showing no new safety concerns, although higher rates of grade 3 or 4 neutropenia were observed in the isatuximab group (23% vs. 7% in the control group).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone as induction therapy for newly diagnosed, transplantation-eligible patients with multiple myeloma (GMMG-HD7): part 1 of an open-label, multicentre, randomised, active-controlled, phase 3 trial. Goldschmidt, H., Mai, EK., Bertsch, U., et al.[2022]

Isatuximab monotherapy was found to be well tolerated and effective in Japanese patients with relapsed/refractory multiple myeloma, with an overall response rate of 36.4% and a clinical benefit rate of 54.5%.

The study identified a recommended dose of 20 mg/kg administered weekly and bi-weekly, with a median progression-free survival of 5.6 months, indicating promising antitumor activity and an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD38 antibody isatuximab monotherapy for Japanese individuals with relapsed/refractory multiple myeloma: An update of the phase 1/2 ISLANDs study. Sunami, K., Fuchida, SI., Suzuki, K., et al.[2023]

In a Phase 1b study involving 73 patients with newly diagnosed multiple myeloma who were ineligible for autologous stem cell transplantation, the combination of isatuximab with bortezomib-lenalidomide-dexamethasone (Isa-VRd) showed a remarkable overall response rate of 98.6%, with over half of the patients achieving a complete response.

While 79.5% of patients experienced grade ≥3 treatment-emergent adverse events, the pharmacokinetics of isatuximab remained consistent, indicating that the combination treatment does not affect its metabolism, supporting further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of isatuximab plus bortezomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma ineligible/with no immediate intent for autologous stem cell transplantation. Ocio, EM., Perrot, A., Bories, P., et al.[2023]

Citations

1.

sarclisa.com

sarclisa.com/newly-diagnosed-trial-results

Newly Diagnosed Trial Results

Trial 3 also measured complete response or better, which means that a patient's multiple myeloma improved with treatment to the point where there are no signs ...

2.

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.

3.

sarclisahcp.com

sarclisahcp.com/imroz-efficacy

IMROZ Efficacy - SARCLISA® (isatuximab-irfc)

Higher 5-year PFS rate with SARCLISA + VRd vs VRd alone: 63% of patients remained alive and progression free at a median follow-up of 60 months. PFS results ...

4.

sarclisa.com

sarclisa.com/previously-treated-trial-results

for adults with previously treated multiple myeloma

In an earlier analysis, at a median follow-up of 20.7 months, 74% (133 of 179 patients) lived progression free with SARCLISA + Kd vs 59% (73 of 123 patients) ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5482100/

A phase 1b study of isatuximab plus lenalidomide and ...

Overall median progression-free survival was 8.5 months. Isatuximab exposure increased in a greater than dose-proportional manner; isatuximab and lenalidomide ...

6.

nature.com

nature.com/articles/s41598-024-83014-1

Comprehensive safety evaluation of isatuximab in multiple ...

The results demonstrated a 7% increased risk of thrombocytopenia (RR = 1.07, 95% CI: 1.01–1.14, p = 0.0213) (Fig. 3a) in the isatuximab therapy.

7.

cancernetwork.com

cancernetwork.com/view/isatuximab-shows-efficacy-acceptable-safety-across-multiple-myeloma-trials

Isatuximab Shows Efficacy, Acceptable Safety Across ...

At a median time to response of 1 month, isatuximab elicited a median duration of response of 10.3 months in patients with multiple myeloma.