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

29 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well carfilzomib, pomalidomide, and dexamethasone work in treating patients with high-risk multiple myeloma. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as pomalidomide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving carfilzomib, pomalidomide, and dexamethasone may work better in treating patients with multiple myeloma.

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.

What data supports the effectiveness of the drug combination Carfilzomib, Pomalidomide, and Dexamethasone for treating multiple myeloma?

Research shows that Pomalidomide combined with low-dose Dexamethasone is effective in prolonging survival and improving response rates in patients with relapsed and refractory multiple myeloma. Carfilzomib has also demonstrated significant activity in similar patient groups, making the combination a promising option for those with limited treatment choices. ^{1 2 3 4 5}

Is the combination of Carfilzomib, Pomalidomide, and Dexamethasone safe for treating multiple myeloma?

The combination of Carfilzomib, Pomalidomide, and Dexamethasone has been studied for safety in patients with relapsed or refractory multiple myeloma. Common side effects included blood-related issues like anemia, and some patients experienced breathing difficulties and mild nerve problems. Serious side effects led to treatment discontinuation in some cases, and there were two deaths due to pneumonia and a blood clot. ^{1 3 4 6 7}

What makes the drug combination of Carfilzomib, Pomalidomide, and Dexamethasone unique for treating multiple myeloma?

This drug combination is unique because it is specifically designed for patients with relapsed or refractory multiple myeloma who have limited treatment options, especially those who are resistant to previous therapies like lenalidomide and bortezomib. Carfilzomib is a second-generation proteasome inhibitor, and Pomalidomide is a novel immunomodulatory drug, both of which have shown high efficacy in difficult-to-treat cases. ^{1 2 4 5 6}

Research Team

Ajay K. Nooka, MD,MPH,FACP

Principal Investigator

Emory University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 (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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

2. New Zealand pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. [2022]

5. Poland pubmed.ncbi.nlm.nih.gov

New drugs in multiple myeloma - role of carfilzomib and pomalidomide. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Phase II study of carfilzomib and dexamethasone therapy for newly diagnosed multiple myeloma. [2020]