Quadruple Drug Therapy for Multiple Myeloma

Not currently recruiting at 2 trial locations

Overseen By Elizabeth O'Donnell, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: Strong CYP inhibitors, inducers

Disqualifiers: COPD, HIV, Hepatitis B/C, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of four drugs to evaluate their effectiveness for people with newly diagnosed multiple myeloma, a type of blood cancer. It targets patients eligible for a stem cell transplant to determine if this drug mix can control the disease before and after the transplant. The combination includes Carfilzomib (Kyprolis), Dexamethasone (Decadron, Dexone, Hexadrol), Isatuximab (Sarclisa, isatuximab-irfc, SAR-650984), and Lenalidomide (Revlimid). Participants will receive different treatments based on their risk level after the initial therapy. This trial may suit individuals recently diagnosed with multiple myeloma who are preparing for high-dose chemotherapy with a stem cell transplant. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use certain strong inhibitors or inducers of specific enzymes, or herbal supplements like Ginkgo biloba and St. John's wort, within 14 days before starting the study treatment.

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

Research has shown that the combination of carfilzomib, dexamethasone, isatuximab, and lenalidomide is generally safe for people with multiple myeloma. In studies involving previously treated patients, this drug mix led to strong and lasting improvements. The safety profile matched what doctors have observed in the past.

Additionally, the FDA has approved isatuximab for use with other drugs in treating multiple myeloma, indicating its safety when used correctly. While side effects can occur, proper care often manages them. Participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this quadruple drug therapy for multiple myeloma because it combines four powerful medications: Carfilzomib, Dexamethasone, Isatuximab, and Lenalidomide, each with a unique way of attacking the cancer. Unlike the standard treatments that might use fewer drugs or different combinations, this approach leverages a synergy between these medications to target the cancer cells more effectively. Carfilzomib is a proteasome inhibitor that disrupts protein breakdown in cancer cells, Isatuximab is an antibody that targets specific proteins on myeloma cells, while Lenalidomide modulates the immune system to fight cancer. This comprehensive attack could potentially enhance treatment effectiveness and improve outcomes for patients, making it a promising option in the fight against multiple myeloma.

What evidence suggests that this trial's drug combination could be effective for multiple myeloma?

Research has shown that a combination of the drugs Carfilzomib, Isatuximab, Lenalidomide, and Dexamethasone, administered during the induction phase of this trial, may effectively treat multiple myeloma. One study found that patients receiving a similar drug combination lived about 41.7 months without disease progression, compared to 20.8 months with a simpler treatment. This combination also resulted in high rates of MRD-negativity, indicating no detectable cancer, which suggests a lower likelihood of recurrence. Additionally, using Lenalidomide as ongoing maintenance therapy, part of the maintenance phase for participants in this trial, has been shown to extend the lives of patients with multiple myeloma. These findings suggest that this drug combination could be a promising treatment option. ^{1 6 7 8 9}

Who Is on the Research Team?

Elizabeth O'Donnell, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed multiple myeloma who meet specific health criteria and are eligible for a stem cell transplant. They must have measurable disease, be in relatively good physical condition (ECOG score of 0-2), and agree to use effective contraception. People can't join if they've had certain treatments for multiple myeloma before, active infections like HIV or hepatitis B/C, recent major surgery or radiation therapy, other medical conditions that could affect the study, or if they're pregnant.

Inclusion Criteria

I have multiple myeloma with symptoms or measurable disease.

I am using reliable birth control methods.

Each subject (or their legally acceptable representative) must sign an informed consent form (ICF)

Exclusion Criteria

You have a history of HIV, hepatitis B, or hepatitis C.

I do not have a stomach or bowel condition that affects how I absorb pills.

I have had treatment for multiple myeloma, except for emergency steroids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive 4 cycles of induction therapy with Carfilzomib, Isatuximab, Lenalidomide, and Dexamethasone. Stem cell collection occurs after 4 cycles, with potential for autologous stem cell transplant.

16 weeks

Weekly visits for drug administration

Maintenance

Participants receive maintenance therapy based on risk stratification for up to two years or until disease progression or unacceptable toxicity.

24 months

Monthly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Carfilzomib
• Dexamethasone
• Isatuximab
• Lenalidomide

Trial Overview The trial is testing a new combination of drugs: Carfilzomib, Isatuximab, Lenalidomide, and Dexamethasone in people with multiple myeloma who can undergo a stem cell transplant. The goal is to see how well this experimental drug mix works against this type of cancer.

How Is the Trial Designed?

Group I: Maintenance-High Risk Experimental Treatment 4 Interventions

Only patients that have achieved a partial response (PR) or better after induction therapy with or without stem cell transplant will continue on to maintenance therapy. The treatment participants will receive for maintenance will be based on the biological features (or cytogenetics) of participants myeloma and categorized into two groups: Standard-risk and High Risk. High Risk: subjects with high risk cytogenetics (deletion (del 17, translocation (t)(4:14), t(14;16), t(14;20), 1q duplications) will receive the following study treatment for up to two years (24 28-day cycles) until progressive disease (PD) or unacceptable toxicity: Lenalidomide 10 mg orally (PO) Day 1-21 Carfilzomib 56 mg/m2 or last tolerated dose IV Days 1, 15 Isatuximab 10 mg/kg IV Day 1

Group II: Maintenance- Standard Risk Experimental Treatment 1 Intervention

Only patients that have achieved a partial response (PR) or better after induction therapy with or without stem cell transplant will continue on to maintenance therapy. The treatment participants will receive for maintenance will be based on the biological features (or cytogenetics) of participants myeloma and categorized into two groups: Standard-risk and High Risk. Standard Risk: subjects without high risk cytogenetics (deletion (del 17, translocation (t)(4:14), t(14;16), t(14;20), 1q duplications) will receive the following study treatment for up to two years (24 28-day cycles) until progressive disease (PD) or unacceptable toxicity: \- Lenalidomide 10 mg orally (PO) Day 1-21

Group III: Induction Experimental Treatment 4 Interventions

All participants will receive 4 cycles of induction therapy. Based on the recommendation of investigators, participants may or may not proceed to an autologous stem cell transplant (SCT) after cycles 1-4. Each cycle is 28 days in length (see dosing details below.) For patient undergoing upfront stem cell transplant (SCT): 4 cycles followed by stem cell collection, high-dose chemotherapy, and autologous SCT followed by 2 cycles (called consolidation). For patients deferring SCT following collection: 4 cycles followed by stem cell collection followed by 4 additional cycles. Carfilzomib: 56 mg/m2 IV on days 1, 8,15 Lenalidomide 25 mg orally (PO) on Days 1-21 Isatuximab: 10 mg/kg IV weekly for cycles 1-2 (days 1, 8, 15, 22), then every 2 weeks for cycles 3-6 (days 1 and 15), and monthly (day 1) thereafter Dexamethasone: 20 mg orally (PO) administered day of and day after carfilzomib and isatuximab (days 1, 2, 8, 9, 15, and 16; days 22 and 23 during cycles 1-2 only).

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

Approved in United States as Kyprolis for:

• Multiple myeloma

Approved in European Union as Kyprolis for:

• Multiple myeloma

Approved in Canada as Kyprolis for:

• Multiple myeloma

Approved in Japan as Kyprolis for:

• Multiple myeloma

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

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

Citations

1. 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.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12030129/

Efficacy and Safety of Isatuximab, Carfilzomib ... Conclusions: These real-world data support the use of IsaKd as a valuable option for len-R MM patients relapsing after the first-line therapy, ...

3. kyprolis-hcp.com kyprolis-hcp.com/combinations/isa-kd-efficacy

Isa-Kd Efficacy | KYPROLIS® (carfilzomib) Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study. Blood Cancer ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006497125002022

Isatuximab, carfilzomib, lenalidomide, and dexamethasone ... Induction with IsaKRD in the MIDAS study yielded the highest pretransplant MRD-negativity rates ever reported in patients with myeloma.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7509

Isatuximab, carfilzomib, lenalidomide, and dexamethasone ... 7509. Background: Patients (pts) with HR NDMM have shown impaired survival outcomes even in the era of modern combination therapies.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38677302/

Isatuximab, carfilzomib, lenalidomide, and dexamethasone ... Isa-KRd induced deep and durable responses in transplant-eligible patients with newly diagnosed multiple myeloma. The treatment proved safe and consistent with ...

7. kyprolis-hcp.com kyprolis-hcp.com/combinations/isa-kd-dosing

Isa-Kd Dosing | KYPROLIS® (carfilzomib) Explore treatment schedules and learn how KYPROLIS® + isatuximabirfc + dexamethasone is dosed 2x weekly. See Full Safety Info.

8. sanofi.com sanofi.com/en/media-room/press-releases/2024/2024-09-20-22-36-34-2949916

Press Release: Sarclisa approved in the US as the first anti ... The US Food and Drug Administration (FDA) has approved Sarclisa (isatuximab) in combination with bortezomib, lenalidomide, and dexamethasone ( ...

9. 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 ...