Carfilzomib + Lenalidomide + Dexamethasone for Multiple Myeloma

Not currently recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Chicago

Must be taking: Lenalidomide

Must not be taking: Antibiotics, Antivirals, Antifungals

Disqualifiers: Progressive disease, POEMS syndrome, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs—carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (Decadron, Dexone, or Hexadrol)—for individuals with multiple myeloma, a type of blood cancer. The researchers aim to determine if this combination is more effective than using lenalidomide alone after a stem cell transplant. They seek participants who have undergone a stem cell transplant for multiple myeloma and remain in stable condition. Participants should not have experienced disease progression after their initial therapy and should not have received more than two prior treatments. This trial may suit those who have had a stem cell transplant and are considering further treatment. As a Phase 3 trial, it represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research has shown that the combination of carfilzomib, lenalidomide, and dexamethasone is generally easy for patients to handle. Studies have found this drug mix effective and safe, even for those who have tried many other treatments. Reports indicate that patients with multiple myeloma, a type of blood cancer, often respond well to this treatment, with serious side effects being rare.

Another study examined a similar combination with an additional drug and found it safe and manageable. This suggests that the carfilzomib-lenalidomide-dexamethasone combo can be tolerable for patients. Overall, existing evidence supports the safety of this treatment, making it a promising option for those considering joining a clinical trial. ^{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 Carfilzomib, Lenalidomide, and Dexamethasone for treating multiple myeloma because it offers a powerful approach by using multiple mechanisms of action. Unlike standard treatments that might focus on a single pathway, this combination targets cancer cells in different ways, potentially leading to more effective results. Carfilzomib is a proteasome inhibitor, which disrupts the protein breakdown in cancer cells, while Lenalidomide modulates the immune system, and Dexamethasone reduces inflammation and further supports cancer cell death. This multi-faceted approach could enhance treatment effectiveness and provide a new hope for patients not fully responding to current therapies.

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

Research has shown that the combination of carfilzomib, lenalidomide, and dexamethasone effectively treats multiple myeloma, a type of blood cancer. In this trial, participants will receive either this experimental combination regimen or lenalidomide alone as the control. Studies have found that the combination helps patients live longer, even if their cancer has returned or is difficult to treat. It is generally well tolerated, even by those who have tried other treatments before. Carfilzomib, one of the drugs in this combination, acts as a proteasome inhibitor, preventing cancer cells from breaking down proteins they need to grow. This combination therapy has shown promising results, making it a potentially strong option for patients with multiple myeloma. ^{1 5 6 7 8}

Who Is on the Research Team?

Andrzej Jakubowiak, MD, PhD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

Adults over 18 with multiple myeloma who've had a stem-cell transplant can join this trial. They should be in good health, have stable disease post-transplant, and agree to birth control measures if applicable. Exclusions include recent radiation or surgery, certain heart conditions, uncontrolled blood pressure or diabetes, active infections, and known HIV/HBV/HCV infection.

Inclusion Criteria

Voluntary written informed consent

FCBP must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during specific time periods

Your white blood cell count, red blood cell count, and platelet count are within certain healthy ranges.

Exclusion Criteria

I have moderate to severe numbness, tingling, or pain in my hands or feet.

Pregnant or lactating females

I have mild to no diarrhea without taking medication for it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a combination of Carfilzomib, Lenalidomide, and Dexamethasone or Lenalidomide alone after stem-cell transplant

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Carfilzomib
• Dexamethasone
• Lenalidomide

Trial Overview The study is testing the effectiveness of combining Carfilzomib with Lenalidomide and Dexamethasone against using only Lenalidomide after a stem-cell transplant in multiple myeloma patients. It's randomized: some get all drugs; others just one.

How Is the Trial Designed?

Group I: Experimental Combination Regimen Experimental Treatment 3 Interventions

Experimental arm using a combination of Carfilzomib, Lenalidomide and Dexamethasone

Group II: Lenalidomide (Control) Active Control 1 Intervention

Treatment with lenalidomide 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?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

In the ENDURANCE trial involving patients with newly diagnosed multiple myeloma, the combination of carfilzomib, lenalidomide, and dexamethasone (KRd) did not improve progression-free survival compared to the standard treatment of bortezomib, lenalidomide, and dexamethasone (VRd).

These findings suggest that KRd may not be a more effective treatment option than the current standard of care for patients with NDMM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib Triplet Fails to Induce Superior PFS in Newly Diagnosed Multiple Myeloma. Skarzynski, J.[2021]

An 82-year-old patient with chemotherapy-naive metastatic castration-resistant prostate cancer showed a long-term response to a very low dose of 40 mg enzalutamide daily, indicating that lower doses may still be effective.

Using lower doses of enzalutamide not only reduces the risk of side effects but could also lower healthcare costs and improve access to treatment, suggesting a need for further studies on the efficacy of these reduced doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep and ongoing response of castrate-resistant prostate cancer on very low-dose enzalutamide in an elderly chemotherapy-naïve patient: a case report. Boerrigter, E., Havenith, T., van Erp, NP., et al.[2021]

In a study involving 792 patients with relapsed multiple myeloma, the combination of carfilzomib with lenalidomide and dexamethasone significantly improved progression-free survival, with a median of 26.3 months compared to 17.6 months for the control group.

The carfilzomib group also showed a higher overall response rate (87.1% vs. 66.7%) and better health-related quality of life, indicating a favorable risk-benefit profile despite similar rates of serious adverse events between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. Stewart, AK., Rajkumar, SV., Dimopoulos, MA., et al.[2022]

Carfilzomib, when used in combination with lenalidomide and dexamethasone, significantly prolongs progression-free survival (PFS) by 8.7 months in patients with relapsed multiple myeloma, based on results from the phase III ASPIRE study involving a multinational patient population.

The combination therapy has a manageable safety profile, with low incidences of severe adverse events, suggesting it is a viable treatment option for patients who have received prior therapies, although overall survival data is still pending.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib Triple Combination Therapy: A Review in Relapsed Multiple Myeloma. Hoy, SM.[2018]

In a phase 3 study involving 466 patients with relapsed or refractory multiple myeloma, the combination of carfilzomib, dexamethasone, and daratumumab (KdD) significantly improved progression-free survival compared to carfilzomib and dexamethasone alone (Kd), with a hazard ratio of 0.63, indicating a 37% reduction in the risk of disease progression.

Despite a higher incidence of grade 3 or higher adverse events in the KdD group (82%) compared to the Kd group (74%), the overall safety profile was considered favorable, with similar rates of treatment discontinuation due to adverse events in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Dimopoulos, M., Quach, H., Mateos, MV., et al.[2020]

In a phase IIb study involving 25 lenalidomide-refractory multiple myeloma patients, the combination of vorinostat, lenalidomide, and dexamethasone showed an overall response rate of 24% and a clinical benefit rate of 80%, indicating significant activity in this challenging patient population.

The most common severe side effects included neutropenia (48%) and thrombocytopenia (32%), highlighting the need for careful monitoring of blood cell counts during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IIb trial of vorinostat in combination with lenalidomide and dexamethasone in patients with multiple myeloma refractory to previous lenalidomide-containing regimens. Sanchez, L., Vesole, DH., Richter, JR., et al.[2018]

In a phase 3 trial involving 239 patients with lower-risk non-del(5q) myelodysplastic syndromes (MDS), lenalidomide showed a higher incidence of grade 3-4 treatment-emergent adverse events (86% vs. 44% for placebo), but did not increase the risk of infections or bleeding events.

Despite the higher incidence of severe adverse events, lenalidomide demonstrated a predictable and manageable safety profile, allowing for continued therapy to maximize clinical benefits in patients who were ineligible or refractory to erythropoiesis-stimulating agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of lenalidomide in patients with lower-risk myelodysplastic syndromes without del(5q): results of a phase 3 trial. Almeida, A., Fenaux, P., Garcia-Manero, G., et al.[2019]

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.