Carfilzomib + Lenalidomide + Dexamethasone for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents

Disqualifiers: Multiple myeloma, Hypertension, Diabetes, 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: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of drugs—carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (Decadron, Dexone, or Hexadrol)—to determine their safety and effectiveness in treating smoldering multiple myeloma (SMM), a blood condition that could progress to full-blown multiple myeloma. The study aims to discover if this drug combination can halt or slow the disease's progression. Individuals diagnosed with high-risk SMM, who are likely to develop multiple myeloma, might be suitable candidates for this trial. Participants will receive the drugs in cycles and undergo close monitoring to assess the treatment's impact. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot be on other investigational agents or have had prior therapy for smoldering multiple myeloma within 4 weeks. It's best to discuss your current medications with the trial team to see if they are compatible with the study requirements.

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

Research shows that the combination of carfilzomib, lenalidomide, and dexamethasone is generally safe and well-tolerated in people with multiple myeloma. Studies have found that even patients with extensive prior treatments manage this combination well. Another study suggested that this combination might be safe and tolerable, with many patients responding positively. Although some side effects can occur, the overall evidence indicates a positive safety profile for these drugs when used together. It is important to note that while carfilzomib is still under study for smoldering multiple myeloma, lenalidomide and dexamethasone are already approved for similar conditions, providing some confidence about their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Carfilzomib, Lenalidomide, and Dexamethasone for treating multiple myeloma because it targets the cancer cells in a unique way. Unlike many standard treatments that work by broadly attacking cancer cells, Carfilzomib specifically inhibits a key protein that helps cancer cells survive, potentially leading to more effective results. This combination also integrates Lenalidomide, which boosts the immune system's ability to fight the cancer, and Dexamethasone, which reduces inflammation and further hampers cancer cell growth. Together, these treatments may offer a more targeted approach with potentially improved outcomes for patients.

What evidence suggests that this trial's treatments could be effective for smoldering multiple myeloma?

Studies have shown that the combination of carfilzomib, lenalidomide, and dexamethasone effectively treats multiple myeloma, a type of blood cancer. This trial includes a treatment arm where participants receive this combination, which has extended survival, particularly for those whose cancer has returned or did not respond to other treatments. Carfilzomib, when combined with the other two drugs, stops cancer cells from growing. Most patients tolerate this combination well, even after many prior treatments. Researchers hope this combination will also be effective for smoldering multiple myeloma, a condition that can progress to multiple myeloma. ^{1 5 6 7 8}

Who Is on the Research Team?

Elizabeth Hill, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults with Smoldering Multiple Myeloma (SMM) likely to progress to multiple myeloma can join. They must understand and sign consent, agree to use contraception, have no other cancer treatments in the last 4 weeks, and meet health criteria including normal organ function and 'high-risk' SMM status.

Inclusion Criteria

My condition is confirmed as Smoldering Multiple Myeloma by a recognized lab.

I can take care of myself but might not be able to do heavy physical work.

I agree to use birth control during the study.

Exclusion Criteria

I have a GI condition that affects my body's ability to absorb medications.

I do not have severe nerve pain or damage.

You are currently taking any other experimental medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction Treatment

Participants receive 8 cycles of combination therapy with carfilzomib, lenalidomide, and dexamethasone

8 months

Frequent visits for blood tests and study visits

Stem Cell Collection

Eligible participants may undergo stem cell collection after 4 cycles of therapy

1-2 weeks

Maintenance Treatment

Participants receive up to 12 cycles of lenalidomide tablets alone if disease has not progressed

12 months

Monthly visits for laboratory evaluations

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 3 months during maintenance and follow-up phases

What Are the Treatments Tested in This Trial?

Interventions

• Carfilzomib
• Dexamethasone
• Lenalidomide

Trial Overview The trial tests a combination of Carfilzomib, Lenalidomide (Revlimid), and Dexamethasone for treating SMM. Participants will undergo eight cycles of treatment with these drugs followed by up to twelve additional cycles with just Lenalidomide if their disease doesn't progress.

How Is the Trial Designed?

Group I: Group B - Carfilzomib with Revlimid and Dexamethasone Experimental Treatment 3 Interventions

Carfilzomib (intravenous (IV), Days 1, 2, 8, 9, 15, and 16 of the 28-day cycle); Revlimid (by mouth (PO), Days 1-21 of the 28-day cycle); and Dexamethasone (PO or IV, Days 1, 2, 8, 9, 15, 16, 22, and 23 of the 28-day cycle)

Group II: Group A - (closed) - Carfilzomib with Revlimid and Dexamethasone Experimental Treatment 3 Interventions

Carfilzomib (intravenous (IV), Days 1, 2, 8, 9, 15, and 16 of the 28-day cycle); Revlimid (by mouth (PO), Days 1-21 of the 28-day cycle; exception: not given on cycle 1 day 1); and Dexamethasone (PO or IV, Days 1, 2, 8, 9, 15, 16, 22, and 23 of the 28-day cycle; exception: not given on cycle 1 day 1)

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2152265025001533

Original Study Real-World Use of carfilzomib-lenalidomide ... Carfilzomib administered as either KRd or Kd was effective and well tolerated, even in patients with multiple prior LOTs, confirming the safety and response ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40447540/

Real-World Use of carfilzomib-lenalidomide ... Conclusion: Carfilzomib administered as either KRd or Kd was effective and well tolerated, even in patients with multiple prior LOTs, confirming the safety and ...

3. haematologica.org haematologica.org/article/view/haematol.2024.285534

Superior outcomes and high-risk features with carfilzomib ... Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma ...

4. nature.com nature.com/articles/s41408-025-01256-2

Carfilzomib prescribing patterns and outcomes for relapsed ... Our findings do not support improved outcomes with twice-weekly carfilzomib in RRMM. K56-1x may provide the best balance of efficacy, safety, and avoidance of ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1411321

Carfilzomib, Lenalidomide, and Dexamethasone for ... The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple ...

6. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2778195

Safety and Effectiveness of Weekly Carfilzomib ... This trial suggests that carfilzomib-lenalidomide-dexamethasone-daratumumab combination therapy may be safe and tolerable and is associated with high rates of ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9240591/

Real-world effectiveness and safety analysis of carfilzomib ... Real-world effectiveness and safety analysis of carfilzomib–lenalidomide–dexamethasone and carfilzomib–dexamethasone in relapsed/refractory multiple myeloma

8. ashpublications.org ashpublications.org/bloodadvances/article/8/19/5012/517073/A-R-R-O-W-2-once-vs-twice-weekly-carfilzomib

A.R.R.O.W.2: once- vs twice-weekly carfilzomib, lenalidomide ... This open-label, phase 3, multicenter, randomized study aimed to demonstrate noninferiority of the overall response rate (ORR) for once-weekly carfilzomib.