Carfilzomib + Pomalidomide + Dexamethasone for Multiple Myeloma

Overseen By Ajay Nooka, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Antivirals, Steroids

Disqualifiers: Smoldering MM, Waldenstrom's, POEMS, 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: 3

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three drugs—carfilzomib (Kyprolis), pomalidomide (Pomalyst or Imnovid), and dexamethasone—to evaluate their effectiveness in treating high-risk multiple myeloma, a type of blood cancer. These drugs aim to stop cancer cells from growing and spreading. The trial seeks participants who have undergone a stem cell transplant for multiple myeloma within the past year and have experienced some improvement. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on other ongoing or prior anti-myeloma therapy, except for bisphosphonates and low-dose corticosteroids for symptom management.

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

Research shows that the combination of carfilzomib, pomalidomide, and dexamethasone is generally well-tolerated by patients with relapsed or refractory multiple myeloma (RRMM). Studies have found that patients do experience side effects, but these are usually manageable. One analysis of two different studies demonstrated that this combination is effective and can be safely used to treat RRMM. Another real-world study highlighted that the side effects can be controlled, allowing patients to benefit from the treatment. Overall, despite some side effects, the combination treatment is considered safe for use in similar patient groups. ^{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, Pomalidomide, and Dexamethasone because it offers a novel approach to treating multiple myeloma. Unlike standard treatments, which often involve agents like Lenalidomide and Bortezomib, this combination includes Pomalidomide, a newer immunomodulatory drug that may work where others have failed. Carfilzomib is a proteasome inhibitor that targets cancer cells more specifically and may cause fewer side effects than older drugs. Together, these medications could potentially improve outcomes by providing a more targeted attack on cancer cells with the promise of enhanced effectiveness and tolerability.

What evidence suggests that this treatment might be an effective treatment for multiple myeloma?

This trial will evaluate the combination of carfilzomib, pomalidomide, and dexamethasone for treating multiple myeloma. Studies have shown that these drugs together are effective, even for patients whose cancer has returned or resisted other treatments. Research indicates that this combination can halt cancer cell growth by blocking essential enzymes. In one study, patients experienced better response rates, with their cancer either shrinking or stopping growth. Another study found that this treatment was generally well-tolerated, suggesting it is both effective and safe for patients. Overall, this drug combination offers hope for individuals with high-risk multiple myeloma. ^{2 4 5 6 7}

Who Is on the Research Team?

Ajay K. Nooka, MD,MPH,FACP

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for adults with high-risk multiple myeloma who've possibly had a stem cell transplant and responded to treatment. They must be able to follow the study plan, use effective birth control, and not have other serious health issues or recent major surgeries. People with certain heart conditions, infections like HIV or hepatitis B/C, previous cancers (except some skin/cervical), allergies to study drugs, or poor reaction to steroids can't join.

Inclusion Criteria

Subject is willing and able to comply with the protocol requirements

All laboratory assessments should be performed within 28 days of initiation of protocol therapy unless otherwise specified

I am committed to using two forms of birth control before, during, and after taking pomalidomide.

Exclusion Criteria

Participants with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to him/her by the study staff

My kidney function is low, with a creatinine clearance under 30 mL/min.

Your platelet count is less than 75,000 cells/mm³ when checked at the screening evaluation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive carfilzomib intravenously, pomalidomide orally, and dexamethasone orally in 28-day cycles

Up to 2 years

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Carfilzomib
• Dexamethasone
• Pomalidomide

Trial Overview The trial tests a combination of three drugs: Carfilzomib (blocks enzymes needed for cancer cells growth), Pomalidomide and Dexamethasone (both chemotherapy agents that kill or stop cancer cells from growing). It aims to see if this mix works better for those with aggressive multiple myeloma.

How Is the Trial Designed?

Group I: Carfilzomib, pomalidomide, dexamethasone Experimental Treatment 3 Interventions

Patients receive carfilzomib IV over 30 minutes on days 1, 8, and 15, pomalidomide PO daily on days 1-21, and dexamethasone PO daily on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

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

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Pomalidomide, combined with low-dose dexamethasone, has been shown to be effective in treating adult patients with relapsed and refractory multiple myeloma, significantly improving progression-free survival and overall response rates compared to high-dose dexamethasone.

The treatment demonstrated a manageable safety profile and was effective across various patient subgroups, including those who were refractory to previous therapies, indicating its potential as a valuable salvage therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: a review of its use in patients with recurrent multiple myeloma. Scott, LJ.[2022]

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]

The novel combination therapy of carfilzomib, pomalidomide, and dexamethasone (CPD) was found to be well-tolerated and highly active in treating patients with relapsed and refractory multiple myeloma, with a total of 32 patients enrolled in the study.

The maximum tolerated dose (MTD) was established at carfilzomib 20/27 mg/m², pomalidomide 4 mg, and dexamethasone 40 mg, although hematologic adverse events were common, affecting over 60% of patients, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Shah, JJ., Stadtmauer, EA., Abonour, R., et al.[2022]

In a phase 2 study involving 72 patients with newly diagnosed multiple myeloma, the combination of carfilzomib and dexamethasone (Kd) achieved a remarkable overall response rate of 90%, with 7% of patients reaching a complete response and 58% achieving a very good partial response.

The treatment was generally well-tolerated, with most adverse events being low grade; however, there was an 11.1% incidence of grade 3 or higher cardiovascular events, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of carfilzomib and dexamethasone therapy for newly diagnosed multiple myeloma. Forsberg, PA., Rossi, AC., Boyer, A., et al.[2020]

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]

Pomalidomide, when combined with low-dose dexamethasone, significantly improves progression-free survival and overall survival in adults with relapsed and refractory multiple myeloma, based on results from multinational phase II and III studies involving patients who had undergone at least two prior treatments.

The treatment has a manageable safety profile, with the most common serious side effects being neutropenia, infections, anemia, and thrombocytopenia, making it a viable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. Hoy, SM.[2018]

Carfilzomib (CFZ) is an effective second-generation proteasome inhibitor approved for treating relapsed and refractory multiple myeloma, showing promising results even in patients with renal insufficiency and no significant impact from cytogenetic abnormalities.

Pomalidomide (POM) is a novel immunomodulatory drug with strong anti-myeloma effects, approved for patients who have not responded to previous therapies, and it has demonstrated high efficacy in those with high-risk cytogenetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New drugs in multiple myeloma - role of carfilzomib and pomalidomide. Jurczyszyn, A., Legieć, W., Helbig, G., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4643003/

Carfilzomib, pomalidomide, and dexamethasone for ... Herein, we report results of a multicenter, phase 1, dose-escalation trial of carfilzomib, pomalidomide, and dexamethasone (CPD) in patients with RRMM. Methods.

2. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/6985/526845/Carfilzomib-Pomalidomide-Dexamethasone-with-and

Carfilzomib, Pomalidomide, Dexamethasone with and without ... This was a multicenter, prospective, real-world cohort study in patients with relapsed/refractory MM in six hospitals from north China since 2022.

3. 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 ...

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. clinicaltrials.gov clinicaltrials.gov/study/NCT05509374?term=Kyprolis&rank=4

Phase II Study of Carfilzomib , Pomalidomide, and ... A phase of research to describe clinical trials that gather more information about a drug's safety and effectiveness by studying different populations and ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7032/526579/Real-World-Effectiveness-and-Safety-Analysis-of

Real-World Effectiveness and Safety Analysis of Carfilzomib ... KPd regimen showed considerable clinical benefits among RRMM in a real-world setting, and the adverse effects after KPd are controllable.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265019314375

Pooled Analysis of 2 Single Arm Studies The triplet combination of carfilzomib, pomalidomide and dexamethasone (KPd) has been shown to be well-tolerated and active in RRMM in two phase 1/2 studies.