Isatuximab + Lenalidomide for Multiple Myeloma

(HEME-18 Trial)

Overseen By Karen Sweiss, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Illinois at Chicago

Must be taking: Lenalidomide

Must not be taking: Investigational drugs

Disqualifiers: Refractory to lenalidomide, CNS involvement, 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

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment for individuals with multiple myeloma, a type of blood cancer. The focus is on using two medications, isatuximab (an antibody therapy) and lenalidomide (an immunomodulatory drug), to help maintain health after a stem cell transplant if the cancer remains detectable. Suitable candidates have a confirmed diagnosis of multiple myeloma, have undergone a stem cell transplant with melphalan, and have at least partially responded to treatment before the transplant. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be willing to take certain blood thinners (like aspirin or warfarin) while receiving lenalidomide.

Is there any evidence suggesting that isatuximab and lenalidomide are likely to be safe for humans?

Research shows that the combination of isatuximab and lenalidomide is generally well-tolerated by people with multiple myeloma. Earlier studies noted a slight increase in the risk of thrombocytopenia, or fewer blood platelets, with isatuximab treatment. This risk increased by 7%, indicating that while some patients might experience this side effect, it is not very common.

Other studies have examined the combination of isatuximab with lenalidomide and found it safe for treating multiple myeloma, especially when used with other drugs like bortezomib. However, the current trial focuses only on isatuximab and lenalidomide. Since isatuximab already treats other forms of multiple myeloma, its safety is well-known, which can reassure those considering joining the trial. Overall, these treatments are considered manageable for patients, with no major safety issues reported so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Isatuximab combined with Lenalidomide for treating multiple myeloma because it offers a unique approach compared to traditional therapies. Most treatments for multiple myeloma, such as proteasome inhibitors and stem cell transplants, focus on different mechanisms. Isatuximab is an antibody that targets a specific protein on the surface of myeloma cells, known as CD38, which may enhance the immune system's ability to attack these cancer cells. When combined with Lenalidomide, which modulates the immune system, this treatment could potentially improve patient outcomes by offering a more targeted and sustained response.

What evidence suggests that isatuximab and lenalidomide might be effective for multiple myeloma?

Research has shown that combining isatuximab and lenalidomide may be promising for treating multiple myeloma. In one study, patients using this combination lived for a median of 8.5 months without disease worsening. Another study found that adding isatuximab to a treatment plan helped patients live longer without disease progression compared to other treatments. These findings suggest that isatuximab and lenalidomide could effectively manage multiple myeloma after stem cell transplants. Participants in this trial will receive both isatuximab and lenalidomide as part of the maintenance therapy under study. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

Adults over 18 with confirmed multiple myeloma, who've had less than two prior therapies and are planning or have recently completed an Autologous Stem Cell Transplant (ASCT). They must be MRD-positive post-ASCT, able to take oral meds, agree to contraception use, and not have certain health conditions that could interfere with the trial.

Inclusion Criteria

Willingness to abstain from heterosexual activity or to use 2 forms of effective contraception from the time of informed consent until 5 months for females, and 1 month for males after treatment discontinuation

I've been mostly active and able to care for myself in the last 30 days.

I am older than 18 years.

Exclusion Criteria

Treatment with any investigational drug within 30 days prior to enrollment

My multiple myeloma has spread to my brain or spinal cord.

I have hepatitis C with a known viral load.

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 if MRD-positive after ASCT

3 years

Isatuximab IV Days 1, 8, 15, 22 Cycle 1; Days 1, 15 Cycles 2-3; Day 1 Cycles 4-39. Lenalidomide PO Days 1-21 Cycles 1-3; Days 1-21 Cycle 4 onwards

Follow-up

Participants are monitored for disease response and MRD status every 12 months

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Isatuximab
• Lenalidomide

Trial Overview The study is testing maintenance therapy using Isatuximab and Lenalidomide in patients who still show minimal residual disease after ASCT. It's a phase II trial aiming to see how effective this combination is for keeping the cancer at bay.

How Is the Trial Designed?

Group I: Isatuximab and Lenalidomide Maintenance Experimental Treatment 2 Interventions

All participants will receive: Isatuximab 10mg/kg IV Days 1,8, 15, 22 Cycle 1 (all cycles 28 days). Isatuximab 10mg/kg Days 1, 15 Cylces 2 and 3. Isatuximab 10mg/kg Day 1, Cylces 4-39. Lenalidomide 10mg PO Days 1-21 Cylces 1-3 (all cycles 28 days) Lenalidomide 15mg PO Days 1-21 Cycle 4 and can continue until disease progression.

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

Huntsman Cancer Institute

Collaborator

Trials

14

Recruited

7,700+

Published Research Related to This Trial

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, 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 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]

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 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, 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]

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 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]

Citations

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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 ...

2. 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 ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2400712

Isatuximab, Bortezomib, Lenalidomide, and ... Isatuximab-VRd was more effective than VRd as initial therapy in patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to ...

4. 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 ...

5. sarclisa.com sarclisa.com/previously-treated-trial-results

for adults with previously treated multiple myeloma At a median follow-up of 44 months, patients lived progression free for a median of 41.7 months with SARCLISA + Kyprolis (carfilzomib) and dexamethasone (Kd) vs ...

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. 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 ...