Isatuximab + Lenalidomide for Multiple Myeloma

Overseen By Muzzaffar Qazilbash, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 3 years

61 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining isatuximab (a monoclonal antibody) and lenalidomide (an immunomodulatory drug) can effectively manage multiple myeloma, a type of blood cancer, after a stem cell transplant. The focus is on high-risk multiple myeloma, which is more likely to return or resist previous treatments. Individuals who have undergone a stem cell transplant and are in at least partial remission, meaning their cancer has improved but not completely disappeared, might be suitable for this study. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that both isatuximab and lenalidomide are generally well-tolerated. The FDA has approved isatuximab for treating multiple myeloma, indicating its safety has been tested. However, studies have found a 7% higher chance of developing thrombocytopenia, a condition with a low blood platelet count, when using isatuximab. Some people might experience this side effect.

Lenalidomide is another commonly used treatment, also approved for multiple myeloma. When combined with isatuximab, these treatments have been used in other studies without major safety concerns. While these treatments have known side effects, they can often be managed with medical help. It is important to discuss potential risks and benefits with a doctor before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about isatuximab and lenalidomide for multiple myeloma because of their unique approach in enhancing the immune system's ability to fight cancer. Isatuximab targets a specific protein called CD38 on the surface of multiple myeloma cells, marking them for destruction by the immune system. When combined with lenalidomide, which boosts the immune system's overall activity, this duo offers a powerful one-two punch against cancer cells. Unlike some standard treatments that might not directly engage the immune system this way, this combination has the potential to improve outcomes for those whose multiple myeloma has returned or stopped responding to other treatments.

What evidence suggests that isatuximab plus lenalidomide might be an effective treatment for multiple myeloma?

Research has shown that combining isatuximab with lenalidomide can effectively treat multiple myeloma, a type of blood cancer. One study involving patients whose cancer had returned or did not respond to treatment found that this combination extended the time patients lived without their cancer worsening, with an average improvement of 8.5 months. Additionally, when used with other drugs like lenalidomide, isatuximab has shown promising results in delaying disease progression. In this trial, participants will receive the combination of isatuximab and lenalidomide after undergoing autologous stem cell transplantation (ASCT). The FDA has already approved this combination for treating multiple myeloma that has recurred or stopped responding to other treatments. ^{2 3 4 6 7}

Who Is on the Research Team?

Muzzaffar Qazilbash, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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.

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

I can communicate in English or another language.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Isatuximab
• Lenalidomide

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.

How Is the Trial Designed?

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+

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

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, an anti-CD38 monoclonal antibody, combined with pomalidomide and dexamethasone, provides a new treatment option for patients with relapsed/refractory multiple myeloma (RRMM) who are resistant to other therapies, addressing a significant unmet clinical need.

The review highlights the safety and efficacy of isatuximab, suggesting it could be an important addition to treatment regimens for RRMM, especially for patients with a poor prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of isatuximab, pomalidomide and dexamethasone for adult patients with relapsed and refractory multiple myeloma. Piggin, A., Prince, HM.[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]

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]

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]

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 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, 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]

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]

Citations

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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.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01749969

NCT01749969 | SAR650984 (Isatuximab), Lenalidomide, ... To evaluate the safety, including immunogenicity, of SAR650984 (isatuximab) in combination with LD in relapsed or refractory multiple myeloma. The severity, ...

3. sarclisa.com sarclisa.com/newly-diagnosed-trial-results

Newly Diagnosed Trial Results At a median follow-up of 60 months, 63% (167 out of 265 patients) lived progression free with SARCLISA + Velcade (bortezomib), Revlimid (lenalidomide), and ...

4. 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 ...

5. sarclisahcp.com sarclisahcp.com/imroz-efficacy

IMROZ Efficacy - SARCLISA® (isatuximab-irfc) In IMROZ study, at a median follow-up time of 60 months, second primary malignancies occurred in 16% of patients treated with SARCLISA, bortezomib, 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. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(25)00039-4/fulltext

Real-World Safety and Tolerability of Rapid, 30-Minutes ... Introduction. The treatment with anti-CD 38 antibodies significantly improved the outcome of patients with multiple myeloma. The anti-CD 38 antibody Isatuximab ...