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

Trial Summary

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.

What data supports the idea that Isatuximab with Stem Cell Transplant for Multiple Myeloma is an effective treatment?

The available research shows that Isatuximab, when combined with other drugs like pomalidomide and dexamethasone, helps patients with multiple myeloma by slowing down the progression of the disease and improving the response to treatment. In one study, nearly all patients responded to the treatment, and more than half achieved a complete response, meaning their cancer was not detectable. This suggests that Isatuximab is an effective option for treating multiple myeloma, especially for those who have tried other treatments before. ^{1 2 3 4 5}

What safety data is available for Isatuximab treatment in multiple myeloma?

Isatuximab, also known as Sarclisa or isatuximab-irfc, has been evaluated in multiple studies for its safety profile in treating multiple myeloma. It is generally well tolerated with a manageable safety profile. Common adverse events include infusion reactions, which are mostly mild (grade 1/2) and occur primarily during the first infusion cycle. No new safety signals have been identified. In phase I and II trials, no dose-limiting toxicities were observed, and the maximum tolerated dose was not reached. The recommended dose is 20 mg/kg administered weekly for the first cycle and every two weeks thereafter. Overall, Isatuximab has shown an acceptable safety and tolerability profile in both monotherapy and combination therapy settings. ^{1 2 6 7 8}

Is the drug Isatuximab a promising treatment for multiple myeloma?

Yes, Isatuximab is a promising drug for treating multiple myeloma. It has been shown to improve patient outcomes by prolonging the time patients live without their disease getting worse and increasing the depth of tumor response. It is used in combination with other drugs and has been approved for patients who have tried other treatments before. The drug is generally well tolerated, and it maintains the quality of life for patients. ^{1 2 3 4 9}

What is the purpose of this trial?

The purpose of this study is to see if Isatuximab can alter the immune system in patients with multiple myeloma or lymphoma upon recovery from the autologous stem cell transplantation. The investigators will see if Isatuximab makes changes to the immune system so that upon recovery from the transplant, the immune system can fight the cancer. This study will have two arms. On one arm (control arm), participants will receive standard transplant procedures and on the other arm (experimental arm), participants will receive Isatuximab in addition to the standard transplant procedures. The assignment to these arms is done randomly (determined by chance, like flipping a coin) by a computer. Each participant will have about 66% chance of getting on the experimental arm and about 33% chance of getting on the control arm.

Research Team

Divaya Bhutani, MD

Principal Investigator

Columbia University

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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

Findings from Research

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 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]

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]

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]

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 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]

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]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

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

2. New Zealand pubmed.ncbi.nlm.nih.gov

Isatuximab: First Approval. [2021]

3. England 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. [2023]

4. England 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. [2022]

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

Isatuximab-Pomalidomide-Dexamethasone Versus Pomalidomide-Dexamethasone in East Asian Patients With Relapsed/Refractory Multiple Myeloma: ICARIA-MM Subgroup Analysis. [2022]

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

Phase I trial of isatuximab monotherapy in the treatment of refractory multiple myeloma. [2021]

7. England 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. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Isatuximab monotherapy in relapsed/refractory multiple myeloma: A Japanese, multicenter, phase 1/2, safety and efficacy study. [2020]

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

Isatuximab: Nursing Considerations for Use in the Treatment of Multiple Myeloma. [2022]