Isa-Rd Combo Therapy for Multiple Myeloma

Recruiting at 4 trial locations

Overseen By Lori Stravers

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Corticosteroids, Antibiotics, others

Disqualifiers: Infection, Heart failure, Amyloidosis, 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: Unknown

Duration: Up to 2 years

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for individuals recently diagnosed with multiple myeloma, a type of blood cancer. The study examines whether lower doses of three drugs—isatuximab (an antibody therapy), lenalidomide, and dexamethasone—remain effective while reducing side effects. It targets individuals who may not tolerate standard, more intense treatments due to concerns about severe side effects. Those with measurable multiple myeloma who have not received more than 28 days of prior treatment might be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant findings.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on medications that are prohibited by the study, you may need to discontinue or replace them with alternatives.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that combining isatuximab, lenalidomide, and dexamethasone has been used in other studies for treating multiple myeloma. These studies indicate that the combination is generally safe, but it can have some serious side effects. For example, isatuximab can sometimes cause severe infections, so healthcare providers monitor patients closely for this.

Lenalidomide and dexamethasone also have their own side effects. Lenalidomide can cause issues with blood, like low white blood cell counts, which can increase the risk of infections. Dexamethasone, a type of steroid, might lead to higher blood sugar levels or mood changes.

The current trial uses lower doses of these drugs to try to reduce side effects. While this combination of drugs hasn't been approved by the FDA for new cases of multiple myeloma at these doses, earlier studies have shown that such combinations are generally well-tolerated. Always discuss any concerns with your healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Researchers are excited about the combination of isatuximab, lenalidomide, and dexamethasone for treating multiple myeloma because it offers a novel approach compared to standard treatments. Isatuximab is a monoclonal antibody that specifically targets the CD38 protein on myeloma cells, which is different from traditional therapies that may not target this protein as directly. This targeted action can potentially enhance the effectiveness of treatment by directly attacking cancer cells while sparing more healthy cells. Additionally, combining isatuximab with lenalidomide and dexamethasone may create a synergistic effect, improving patient outcomes more than using these drugs individually.

What evidence suggests that this combination therapy could be effective for multiple myeloma?

Research has shown that combining isatuximab with lenalidomide and dexamethasone is promising for treating multiple myeloma, a type of blood cancer. Studies have found that adding isatuximab to these treatments helps patients live longer without their disease worsening. Specifically, patients receiving this combination experienced longer periods without cancer progression compared to those who did not receive isatuximab. This suggests that isatuximab can enhance the effectiveness of these existing medicines. The trial will administer the combination of isatuximab, lenalidomide, and dexamethasone to all participants, using lower doses to minimize side effects, with the aim of replicating the combination's success seen in other studies for newly diagnosed patients. ^{3 6 7 8 9}

Who Is on the Research Team?

Sascha Tuchman, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for older or frail patients with newly diagnosed multiple myeloma who haven't had more than 28 days of anti-myeloma therapy. They must be at high risk for severe side effects from standard treatments, have measurable MM and related organ dysfunction, and show adequate organ function. Women of childbearing age must use birth control.

Inclusion Criteria

Willing and able to adhere to the study visit schedule and other protocol requirements based on the judgement of the investigator or protocol designee.

Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information (PHI).

My organ functions and lab tests meet the required standards.

Exclusion Criteria

I have not had a serious infection or needed antibiotics in the last 14 days.

Receiving other investigational agents less than 14 days or 5 half-lives of first dose of therapy on this protocol, whichever is longer.

I have a stomach or bowel condition that affects how I absorb pills or tolerate certain medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive isatuximab, lenalidomide, and dexamethasone with 28-day cycles. Isatuximab is administered for two years, dexamethasone weekly for the first eight cycles, and lenalidomide continued as maintenance until disease progression or unacceptable toxicity.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment until death or full withdrawal from the study. Those withdrawn for adverse events are followed for resolution or stabilization of the adverse event(s).

Until death or full withdrawal

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone
• Isatuximab
• Lenalidomide

Trial Overview

The study tests a combination of isatuximab, lenalidomide, and dexamethasone at lower doses than usual to see if it's safe and effective for treating new multiple myeloma cases while minimizing side effects. This approach isn't FDA-approved yet.

How Is the Trial Designed?

Group I: Single Arm Experimental Treatment 3 Interventions

All subjects will receive the same treatment on the study, consisting of isatuximab, lenalidomide, and dexamethasone with 28 days cycles.

Dexamethasone is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases
• Immune system disorders

Approved in United States as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders
• Neoplastic diseases
• Nervous system disorders

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

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

Published Research Related to This Trial

In the phase 3 ICARIA-MM trial, isatuximab combined with pomalidomide-dexamethasone significantly improved median progression-free survival (mPFS) in high-risk multiple myeloma patients, showing 7.5 months compared to 3.7 months with standard treatment.

Despite a higher incidence of grade ≥3 adverse events in high-risk patients receiving isatuximab (95.7% vs. 67.6% in the control group), the treatment did not lead to increased discontinuation or treatment-related mortality, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subgroup analysis of ICARIA-MM study in relapsed/refractory multiple myeloma patients with high-risk cytogenetics. Harrison, SJ., Perrot, A., Alegre, A., 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 phase 3 study involving 307 patients with relapsed and refractory multiple myeloma, the combination of isatuximab, pomalidomide, and dexamethasone significantly improved progression-free survival (11.5 months) compared to pomalidomide and dexamethasone alone (6.5 months).

The most common side effects included infusion reactions and upper respiratory infections, with a low incidence of treatment-related deaths, indicating that isatuximab is a relatively safe and effective treatment option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Attal, M., Richardson, PG., Rajkumar, SV., et al.[2020]

In the ICARIA-MM trial involving 307 patients with relapsed/refractory multiple myeloma, the combination of isatuximab, pomalidomide, and dexamethasone significantly improved median progression-free survival (PFS) compared to pomalidomide and dexamethasone alone, with PFS of 12.3 months versus 7.8 months for those with 2-3 prior therapies, and 9.4 months versus 4.3 months for those with more than 3 prior therapies.

The overall response rate (ORR) was also notably higher in patients receiving isatuximab-pomalidomide-dexamethasone, with rates of 59.0% in lenalidomide-refractory patients compared to 31.4% in the control group, demonstrating the efficacy of isatuximab across different refractory statuses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab plus pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma according to prior lines of treatment and refractory status: ICARIA-MM subgroup analysis. Bringhen, S., Pour, L., Vorobyev, V., et al.[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]

In a phase 2 study involving 164 patients with relapsed/refractory multiple myeloma, the combination of isatuximab and dexamethasone showed a significantly higher overall response rate (43.6%) compared to isatuximab alone (23.9%).

The addition of dexamethasone did not increase safety concerns, as the incidence of serious adverse events, including infections, was similar between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma. Dimopoulos, M., Bringhen, S., Anttila, P., 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]

Citations

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sarclisa.com

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Newly Diagnosed Trial Results

Trial 3: SARCLISA + Velcade®, Revlimid®, and dexamethasone (VRd) helped more patients live progression free vs VRd alone.

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sarclisahcp.com

sarclisahcp.com/imroz-efficacy

IMROZ Efficacy - SARCLISA® (isatuximab-irfc)

See the IMROZ trial results and design for SARCLISA + bortezomib, lenalidomide, and dexamethasone (VRd) vs VRd alone. See Important Safety & Prescribing ...

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.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40284030/

Results from the Multicenter, Real-Life AENEID Study

These real-world data support the use of IsaKd as a valuable option for len-R MM patients relapsing after the first-line therapy, including ASCT and ...

5.

sarclisa.com

sarclisa.com/previously-treated-trial-results

for adults with previously treated multiple myeloma

Patients lived progression free for a median of 41.7 months with SARCLISA + Kyprolis (carfilzomib) and dexamethasone (Kd) vs 20.8 months with Kd alone.

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39841461/

analysis of the MIDAS trial - PubMed - NIH

Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone Induction in Newly Diagnosed Myeloma: Analysis of the MIDAS Trial

7.

sarclisa.com

sarclisa.com/possible-side-effects

Possible Side Effects

SARCLISA can cause infections that are severe, life-threatening, or that may lead to death. Your healthcare provider will monitor you for signs and symptoms of ...

8.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2024/761113s014lbl.pdf

SARCLISA® (isatuximab-irfc) injection, for intravenous use

The safety of SARCLISA was evaluated in ICARIA-MM, a randomized, open-label clinical trial in patients with previously treated multiple myeloma. Patients ...

9.

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 ...

Recent early clinical trial data suggested the safety of rapid, 30-minute administration of intravenous isatuximab in myeloma patients.