Isatuximab + Standard Therapy for Multiple Myeloma

Recruiting at 9 trial locations

Overseen By Aniba Khan

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Canadian Myeloma Research Group

Must not be taking: Anti-CD38 antibodies

Disqualifiers: Uncontrolled diabetes, Cardiovascular disease, 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: 8

72 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase II multi-center, open label, single arm study to evaluate the safety and efficacy of Isatuximab administered intravenously in combination with CyBorD induction treatment and Lenalidomide maintenance treatment in a 28-day long cycle in autologous stem cell transplant-eligible patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it allows the use of certain corticosteroids under specific conditions, so it's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug Isatuximab for treating multiple myeloma?

Research shows that Isatuximab, when combined with other drugs like pomalidomide and dexamethasone or carfilzomib and dexamethasone, helps patients with multiple myeloma live longer without their disease getting worse. It also improves the depth of tumor response and maintains quality of life, making it a valuable option for those with relapsed or hard-to-treat multiple myeloma. ^{1 2 3 4 5}

Is isatuximab safe for use in humans?

Isatuximab, also known as Sarclisa, has been generally well tolerated in clinical trials for multiple myeloma, with manageable side effects. Common side effects include mild to moderate infusion reactions, and no new safety concerns have been identified in combination therapies. ^{1 4 5 6 7}

How is the drug Isatuximab unique in treating multiple myeloma?

Isatuximab is unique because it is a monoclonal antibody that targets the CD38 protein on cancer cells, and when combined with other drugs like pomalidomide and dexamethasone, it has been shown to significantly extend the time patients live without their disease worsening. This combination is particularly beneficial for patients whose multiple myeloma has returned or not responded to previous treatments. ^{1 3 4 8 9}

Eligibility Criteria

This trial is for adults aged 18-75 with newly diagnosed symptomatic Multiple Myeloma who have a life expectancy of at least 9 months and meet specific health criteria. Participants must not be pregnant, breastfeeding, or planning to become pregnant and agree to use effective contraception methods. They should not have had prior treatments for MM except certain steroids, no known HIV/hepatitis B/C, CNS involvement, or severe heart conditions.

Inclusion Criteria

Your platelet count is at least 70 x 10^9/L (or at least 50 x 10^9/L if you have a lot of plasma cells in your bone marrow).

Your corrected serum calcium level is less than or equal to 3.5 mmol/L.

Your hemoglobin level is at least 80 grams per liter. If it's lower, you can still participate if you receive a blood transfusion.

Exclusion Criteria

I plan to try for a child during or within 3 months after the study.

Your heart's electrical activity, as measured by an ECG test, shows that it takes too long for your heart to recharge between beats (more than 470 milliseconds).

Any other condition that, in the Investigator's opinion, would contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive Isatuximab in combination with CyBorD for four 28-day cycles

16 weeks

4 visits per cycle (in-person)

Stem Cell Mobilization and Transplantation

Stem cell mobilization followed by high dose chemotherapy and autologous stem cell transplantation

8 weeks

Maintenance Treatment

Isatuximab and Lenalidomide maintenance treatment starting at day 100 post-transplant

Ongoing

4 visits in cycle 1, 2 visits in cycles 2-3, 1 visit in subsequent cycles (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

100 days

Treatment Details

Interventions

• Isatuximab

Trial Overview The study tests Isatuximab combined with CyBorD induction treatment and Lenalidomide maintenance in patients eligible for autologous stem cell transplant. It's an open-label phase II trial where all participants receive the same treatment over a series of 28-day cycles to assess safety and effectiveness.

Participant Groups

Group I: Isatuximab with CyBorD and Lenalidomide Maintenance Experimental Treatment 1 Intervention

This is a single arm study of Isatuximab administered intravenously in combination with cyclophosphamide, bortezomib and dexamethasone (CyBorD), and Lenalidomide maintenance treatment

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?

Canadian Myeloma Research Group

Lead Sponsor

Trials

7

Recruited

500+

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]

The combination of isatuximab and carfilzomib was well tolerated in 33 patients with relapsed and refractory multiple myeloma, showing no unexpected toxicity and an overall response rate of 70%.

With a median follow-up of 26.7 months, the treatment resulted in a median progression-free survival of 10.1 months, indicating its effectiveness even in heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1b trial of isatuximab, an anti-CD38 monoclonal antibody, in combination with carfilzomib as treatment of relapsed/refractory multiple myeloma. Martin, TG., Shah, N., Richter, J., et al.[2021]

Isatuximab, a humanized IgG1 monoclonal antibody targeting CD38, was approved by the FDA in March 2020, adding a new option for treating multiple myeloma.

The use of monoclonal antibodies like isatuximab, along with other therapies such as immunomodulatory drugs and proteasome inhibitors, allows for more complex treatment regimens (3 to 4 drugs) while maintaining acceptable safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic potential of isatuximab in the treatment of multiple myeloma: Evidence to date. Richter, J., Sanchez, L., Thibaud, S.[2021]

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 3 trial with 302 patients suffering from relapsed/refractory multiple myeloma, the combination of isatuximab with carfilzomib-dexamethasone significantly prolonged progression-free survival (PFS) to a median of 35.7 months compared to 19.2 months for carfilzomib-dexamethasone alone.

The addition of isatuximab also resulted in higher rates of complete response (44.1% vs 28.5%) and minimal residual disease negativity (33.5% vs 15.4%), indicating improved efficacy without compromising safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study. Martin, T., Dimopoulos, MA., Mikhael, J., et al.[2023]

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 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]

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

Phase 1b trial of isatuximab, an anti-CD38 monoclonal antibody, in combination with carfilzomib as treatment of relapsed/refractory multiple myeloma. [2021]

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

Therapeutic potential of isatuximab in the treatment of multiple myeloma: Evidence to date. [2021]

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

Isatuximab: First Approval. [2021]

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

Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study. [2023]

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

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

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]

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

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