Isatuximab + Lenalidomide for Multiple Myeloma

Recruiting in Palo Alto (17 mi)

Overseen by Muzzaffar Qazilbash, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: M.D. Anderson Cancer Center

Must be taking: Isatuximab, Lenalidomide

Must not be taking: Thalidomide, Lenalidomide

Disqualifiers: Active infection, Uncontrolled hypertension, HIV, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

To learn if isatuximab can help to control highrisk MM when given in combination with lenalidomide after an autologous stem cell transplantation (ASCT).

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking other investigational drugs within 14 days before starting the study.

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

Research shows that Isatuximab, when combined with other drugs like lenalidomide, can improve the response rate and delay the progression of multiple myeloma, a type of blood cancer. In studies, this combination was generally well tolerated and showed promising results in patients who had already tried other treatments. ^{1 2 3 4 5}

Is the combination of Isatuximab and Lenalidomide safe for humans?

The combination of Isatuximab and Lenalidomide has been generally well tolerated in clinical trials for multiple myeloma, with manageable side effects. Common side effects include infusion-related reactions, infections, and low blood cell counts, but these were mostly mild to moderate in severity. ^{1 2 6 7 8}

How is the drug Isatuximab + Lenalidomide unique for treating multiple myeloma?

Isatuximab + Lenalidomide is unique because it combines an anti-CD38 monoclonal antibody (Isatuximab) with Lenalidomide, which is commonly used for relapsed or refractory multiple myeloma. This combination has shown to improve progression-free survival and tumor response in patients who have already undergone multiple treatments, offering a new option for those with limited alternatives. ^{1 2 6 8 9}

Research Team

Muzzaffar Qazilbash, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults aged 18-70 with newly diagnosed high-risk multiple myeloma who've had a partial response or better after stem cell transplant. They must have adequate organ function, agree to birth control measures, and not be pregnant or breastfeeding. Excluded are those with progressing myeloma, recent major surgery, active infections requiring treatment, known drug allergies relevant to the study drugs, or HIV/hepatitis.

Inclusion Criteria

Your blood counts need to meet certain requirements.

I am between 18 and 70 years old with newly diagnosed myeloma.

You must have a detectable disease as defined by specific criteria when you are diagnosed.

Exclusion Criteria

I have allergies to drugs similar to the ones used in this study.

I do not have any uncontrolled illnesses.

Patients receiving any other investigational agents within specific timeframes

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive isatuximab and lenalidomide maintenance therapy after ASCT

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

1 visit per year

Treatment Details

Interventions

• Isatuximab (Monoclonal Antibodies)
• Lenalidomide (Immunomodulatory agents)

Trial Overview The trial tests if adding Isatuximab to Lenalidomide as maintenance therapy post-stem cell transplant can help control high-risk multiple myeloma. Participants will receive this combination treatment and their disease progression will be monitored.

Participant Groups

Group I: isatuximab plus lenalidomide after an autologous stem cell transplantation (ASCT) Experimental Treatment 2 Interventions

Both isatuximab and lenalidomide are FDA approved and commercially available for the treatment of relapsed or refractory MM (MM that has come back or stopped responding to treatment). Participants will begin taking the study drugs about 60-180 days after your ASCT. Participants may receive the study drugs for about 3 years. After that, participants will have follow-up visits 1 time a year for the 3 years after your last dose of study drugs

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Dr. Peter WT Pisters

M.D. Anderson Cancer Center

Chief Executive Officer since 2017

MD from University of Western Ontario

Dr. Jeffrey E. Lee

M.D. Anderson Cancer Center

Chief Medical Officer

MD from Stanford University School of Medicine

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

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]

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 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 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 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 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 combined with carfilzomib and dexamethasone (Isa-Kd) demonstrated significantly better progression-free survival (PFS) compared to daratumumab combined with lenalidomide and dexamethasone (Dara-Rd) in patients with relapsed and/or refractory multiple myeloma, based on a matching-adjusted indirect comparison of 179 patients from the IKEMA trial and 286 patients from the POLLUX trial.

Patients receiving Isa-Kd experienced lower rates of treatment-emergent adverse events (TEAEs) compared to those on Dara-Rd, indicating a potentially safer profile for Isa-Kd in this treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect comparison of isatuximab plus carfilzomib and dexamethasone with daratumumab plus lenalidomide and dexamethasone in relapsed multiple myeloma. Richter, J., Lin, PL., Garcia-Horton, V., et al.[2023]

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

A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma. [2021]

3. 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]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

An evaluation of isatuximab, pomalidomide and dexamethasone for adult patients with relapsed and refractory multiple myeloma. [2022]

6. 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]

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

Isatuximab: First Approval. [2021]

8. England 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. [2023]

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

Matching-adjusted indirect comparison of isatuximab plus carfilzomib and dexamethasone with daratumumab plus lenalidomide and dexamethasone in relapsed multiple myeloma. [2023]