Isatuximab with Stem Cell Transplant for Multiple Myeloma

Recruiting at 1 trial location

Overseen By Research Nurse Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Divaya Bhutani

Must not be taking: CD38 antibodies

Disqualifiers: Severe allergies, Uncontrolled illness, HIV, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 weeks

39 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Isatuximab, a monoclonal antibody, combined with a standard stem cell transplant, can enhance the immune system's ability to fight multiple myeloma or certain types of lymphoma. The researchers aim to determine if Isatuximab can modify the immune system to better attack cancer after transplant recovery. Participants will be randomly assigned to two groups: one will receive the standard transplant treatment, while the other will receive Isatuximab in addition to the standard treatment. Individuals with multiple myeloma or specific types of relapsed or resistant lymphoma, who have not undergone similar treatment in the past year, may be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to advancements in cancer treatment.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received a CD38 antibody in the last 12 months or any investigational agents in the last 8 weeks.

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

Research has shown that Isatuximab, a treatment for multiple myeloma, is generally safe. One study found a small 7% increase in the risk of thrombocytopenia, a condition where patients might have fewer platelets, which help blood clot. Despite this, patients generally tolerated Isatuximab well. In real-world use, the drug was administered quickly over 30 minutes without needing to slow down the process, indicating that the treatment is manageable for patients. ^{1 2 3 4 5}

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

Unlike the standard treatments for multiple myeloma, which often include medications like bortezomib, lenalidomide, and dexamethasone, Isatuximab offers a unique approach by targeting a specific protein on the surface of myeloma cells called CD38. This monoclonal antibody helps the immune system identify and destroy cancer cells more effectively. Researchers are excited about Isatuximab because it has the potential to work synergistically with stem cell transplants, possibly enhancing the overall effectiveness of the treatment and improving patient outcomes.

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

Research has shown that Isatuximab may effectively treat multiple myeloma, a type of blood cancer. In studies, patients receiving Isatuximab with other medications experienced longer periods without cancer progression. For example, 63% of patients remained alive and their cancer had not progressed five years after treatment when Isatuximab was used with a combination of drugs called VRd. Another study found that 74% of patients lived without cancer worsening for about 21 months when Isatuximab was combined with another drug combo called Kd. In this trial, one group of participants will receive Isatuximab in addition to standard procedures for stem cell transplants, while another group will receive only the standard procedures. These results suggest that Isatuximab could improve outcomes for patients undergoing stem cell transplants for multiple myeloma. ^{3 5 6 7 8}

Who Is on the Research Team?

Divaya Bhutani, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with multiple myeloma or lymphomas, including Hodgkin's and non-Hodgkin's types, who are undergoing their first stem cell transplant. They should not have used CD38 antibodies in the past year or be HIV-positive. Pregnant women and those with severe allergies to Isatuximab-like compounds, uncontrolled illnesses, or recent use of investigational drugs cannot participate.

Inclusion Criteria

You are expected to live for at least 6 more months.

I have a specific type of blood cancer and am at a certain stage of treatment.

I am about to have my first stem cell transplant.

Exclusion Criteria

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

I have been treated with a CD38 antibody in the past year.

I am HIV-positive.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo autologous stem cell transplantation with or without Isatuximab

4-6 weeks

Follow-up

Participants are monitored for immune system changes and adverse events

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Isatuximab

Trial Overview

The study tests if adding Isatuximab to standard stem cell transplant procedures can better help the immune system fight cancer in patients recovering from transplantation. Participants will be randomly assigned to either receive standard care (control arm) or standard care plus Isatuximab (experimental arm).

How Is the Trial Designed?

Group I: Standard procedures Experimental Treatment 1 Intervention

Subjects will receive standard procedures for transplant.

Group II: Isatuximab and Standard Procedures Experimental Treatment 1 Intervention

Subjects will receive the study drug Isatuximab in addition to standard procedures for transplant

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?

Divaya Bhutani

Lead Sponsor

Trials

1

Recruited

40+

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

Isatuximab is an IgG1 monoclonal antibody that targets CD38 on cancer cells and has been approved in the USA for treating multiple myeloma in patients who have undergone at least two prior therapies.

The approval of isatuximab, in combination with pomalidomide and dexamethasone, marks a significant advancement in treatment options for adult patients with relapsed and refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab: First Approval. Dhillon, S.[2021]

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]

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]

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 subgroup analysis of 36 East Asian patients with relapsed/refractory multiple myeloma, the combination of isatuximab, pomalidomide, and dexamethasone (Isa-Pd) showed improved progression-free survival compared to pomalidomide and dexamethasone alone, with a median progression-free survival not reached in the Isa-Pd group versus 7.9 months in the Pd group.

The safety profile of Isa-Pd in East Asian patients was consistent with the overall population, although a higher incidence of Grade ≥ 3 neutropenia was observed, indicating that while the treatment is effective, monitoring for this side effect is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab-Pomalidomide-Dexamethasone Versus Pomalidomide-Dexamethasone in East Asian Patients With Relapsed/Refractory Multiple Myeloma: ICARIA-MM Subgroup Analysis. Sunami, K., Ikeda, T., Huang, SY., et al.[2022]

Isatuximab, a CD38 monoclonal antibody, is effective for treating adults with relapsed/refractory multiple myeloma, particularly in combination with pomalidomide and dexamethasone after at least two prior therapies.

Nursing care for patients receiving isatuximab involves careful monitoring for adverse events like infusion reactions and neutropenia, which is crucial for providing effective patient education and management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab: Nursing Considerations for Use in the Treatment of Multiple Myeloma. Wilmoth, J., Colson, K., Dubin, F., et al.[2022]

In a phase I study involving 84 patients with relapsed/refractory multiple myeloma, isatuximab showed a manageable safety profile, with infusion reactions occurring in 51% of patients but mostly being mild (grade 1/2).

Isatuximab demonstrated clinical activity, with an overall response rate of 23.8% at doses of 10 mg/kg or higher, including one complete response, indicating its potential as an effective treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of isatuximab monotherapy in the treatment of refractory multiple myeloma. Martin, T., Strickland, S., Glenn, M., et al.[2021]

Isatuximab, an anti-CD38 monoclonal antibody, was found to be well tolerated and effective in treating heavily pretreated relapsed/refractory multiple myeloma, with an overall response rate of 36.4% in a phase 2 trial involving 28 patients.

The most common side effects were mild infusion reactions occurring in 42.9% of patients, indicating a manageable safety profile, while the median progression-free survival was 4.7 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab monotherapy in relapsed/refractory multiple myeloma: A Japanese, multicenter, phase 1/2, safety and efficacy study. Sunami, K., Suzuki, K., Ri, M., et al.[2020]

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]

Citations

1.

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 ...

2.

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 ...

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.

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 ...

5.

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) ...

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.

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S2152265025000394

Real-World Safety and Tolerability of Rapid, 30-Minutes ...

The rapid 30-minutes intravenous isatuximab was adequately tolerated in all patients. No patient was changed back to the standard administration rate.