29 Participants Needed

Triple Drug Therapy for Multiple Myeloma

Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: City of Hope Medical Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well leflunomide, pomalidomide, and dexamethasone work for the treatment of multiple myeloma that has come back (relapsed) or does not respond to treatment (refractory). Leflunomide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with pomalidomide, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as 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 leflunomide with pomalidomide and dexamethasone may work better in treating multiple myeloma compared to pomalidomide and dexamethasone alone.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot use other anti-myeloma therapies besides leflunomide, pomalidomide, and dexamethasone. It's best to discuss your current medications with the study team.

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

Research shows that the combination of pomalidomide and low-dose dexamethasone is effective for patients with relapsed and refractory multiple myeloma, improving survival and response rates compared to high-dose dexamethasone alone. This suggests that pomalidomide and dexamethasone are effective components in treating this condition.12345

Is the triple drug therapy for multiple myeloma safe for humans?

The combination of pomalidomide and low-dose dexamethasone has been shown to have a manageable safety profile in patients with relapsed and refractory multiple myeloma. Common side effects include neutropenia (low white blood cell count), infections, anemia (low red blood cell count), and thrombocytopenia (low platelet count), but these were generally manageable.12567

What makes the triple drug therapy for multiple myeloma unique?

This triple drug therapy combines Dexamethasone, Leflunomide, and Pomalidomide, offering a novel approach by using Leflunomide's unique ability to inhibit immune cell proliferation, which is not commonly used in multiple myeloma treatments. This combination may provide a new mechanism of action compared to standard therapies.89101112

Research Team

MA

Michael A. Rosenzweig

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults with multiple myeloma that has returned or isn't responding to treatment. They must have had at least one prior therapy, be in relatively good health (ECOG <=2), and not planning a transplant soon. Participants need measurable levels of cancer markers in their blood/urine and adequate organ function. Women of childbearing age must test negative for pregnancy and agree to birth control.

Inclusion Criteria

I have been diagnosed with multiple myeloma and it can be measured.
Assent, when appropriate, will be obtained per institutional guidelines
Agreement to allow the use of archival tissue from diagnostic tumor biopsies
See 21 more

Exclusion Criteria

I have been diagnosed with rheumatoid arthritis.
You have tested positive for hepatitis A, B, or C.
I am not using other myeloma treatments besides leflunomide, pomalidomide, and dexamethasone.
See 17 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive leflunomide, pomalidomide, and dexamethasone in 28-day cycles

Up to 1 year
Monthly visits for each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year
Follow-up at 30 days post-treatment, then every 3 months

Treatment Details

Interventions

  • Dexamethasone
  • Leflunomide
  • Pomalidomide
Trial OverviewThe study tests the combination of leflunomide, pomalidomide, and dexamethasone against multiple myeloma. Leflunomide may block enzymes needed by cancer cells; pomalidomide could alter the immune system's response to tumor cells; dexamethasone aims to stop cancer cell growth.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (leflunomide, pomalidomide, dexamethasone)Experimental Treatment3 Interventions
Patients receive leflunomide PO on days 1-28, pomalidomide PO on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

🇪🇺
Approved in European Union as Dexamethasone for:
  • Inflammation
  • Allergic reactions
  • Respiratory diseases
  • Skin conditions
  • Eye diseases
  • Immune system disorders
🇺🇸
Approved in United States as Dexamethasone for:
  • Inflammatory conditions
  • Allergic states
  • Respiratory diseases
  • Blood disorders
  • Neoplastic diseases
  • Nervous system disorders
🇨🇦
Approved in Canada as Dexamethasone for:
  • Inflammation
  • Allergic reactions
  • Respiratory diseases
  • Skin conditions
  • Eye diseases
🇯🇵
Approved in Japan as Dexamethasone for:
  • Inflammatory conditions
  • Allergic states
  • Respiratory diseases
  • Blood disorders

Find a Clinic Near You

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials
614
Recruited
1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

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.
Pomalidomide: a review of its use in patients with recurrent multiple myeloma.Scott, LJ.[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.
Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma.Hoy, SM.[2018]
A subgroup analysis from two phase III clinical trials demonstrated that combining lenalidomide with dexamethasone is more effective than using dexamethasone alone for patients with relapsed or refractory multiple myeloma who had prior treatment with thalidomide.
This finding suggests that the lenalidomide and dexamethasone combination could be a more beneficial treatment option for these patients, potentially improving their outcomes in clinical practice.
Hematology: Lenalidomide plus dexamethasone is effective in multiple myeloma.Meijer, E., Sonneveld, P.[2021]

References

Pomalidomide: a review of its use in patients with recurrent multiple myeloma. [2022]
Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. [2018]
Hematology: Lenalidomide plus dexamethasone is effective in multiple myeloma. [2021]
[The effect of cyclophosphamide, thalidomide and dexamethasone combination therapy in relapsed/refractory multiple myeloma]. [2014]
Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma. [2022]
Pomalidomide for the treatment of relapsed-refractory multiple myeloma: a review of biological and clinical data. [2014]
Pomalidomide therapy for multiple myeloma and myelofibrosis: an update. [2021]
[Efficacy of leflunomide]. [2018]
Experiences with leflunomide in solid organ transplantation. [2022]
Leflunomide therapy following penetrating keratoplasty in the rat. [2019]
Efficacy and safety of leflunomide in treatment of steroid-dependent and steroid-resistant adult onset minimal change disease. [2018]
Leflunomide for the treatment of rheumatoid arthritis. [2019]