Leflunomide, Pomalidomide, and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma

NCT04508790 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 19418NCI-2020-01962
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• Overall response

  Clopper Pearson binomial 95% confidence intervals will be calculated.

  Up to 1 year

Secondary Outcomes (6)

• Incidence of adverse events

  Up to 30 days after last dose

• Response duration

  Up to 1 year

• Depth of response

  Up to 1 year

• Clinical benefit response

  Up to 1 year

• Overall survival

  Up to 1 year

Study Arms (1)

Treatment (leflunomide, pomalidomide, dexamethasone)

EXPERIMENTAL

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.

Drug: Dexamethasone; Drug: Leflunomide; Drug: Pomalidomide

Interventions

Dexamethasone DRUG

Given PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Treatment (leflunomide, pomalidomide, dexamethasone)

Leflunomide DRUG

Given PO

Also known as: Arava, SU101

Treatment (leflunomide, pomalidomide, dexamethasone)

Pomalidomide DRUG

Given PO

Also known as: 4-Aminothalidomide, Actimid, CC-4047, Imnovid, Pomalyst

Treatment (leflunomide, pomalidomide, dexamethasone)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Eastern Cooperative Oncology Group (ECOG) =\< 2
• Life expectancy \> 3 months
• Diagnosis of multiple myeloma with measurable disease as defined by:
• M-protein quantities \>= 0.5 g/dL by serum protein electrophoresis (sPEP) or
• \>= 200 mg/24 hour urine collection by urine protein electrophoresis (uPEP) or
• Serum free light chain (FLC) \> 10.0 mg/dL involved light chain and an abnormal kappa/lambda ration in subjects without detectable serum or urine M-protein or
• For subjects with immunoglobulin class A (IgA) myeloma whose disease can only be reliably measured by quantitative immunoglobulin measurement, a serum IgA level \>= 0.50 g/dL
• Relapsed or refractory to at least 1 prior line of therapy, including both a proteasome inhibitor and an immunomodulatory drug, and for whom transplant is not recommended. Participants may opt for a delayed transplant at a later time, if appropriate
• Fully recovered from the acute toxic effects (except alopecia) to =\< grade 2 to prior anti-cancer therapy
• Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
• NOTE: Screening ANC should be independent of granulocyte- and granulocyte/macrophage colony stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of pegylated G-CSF for at least 2 weeks

You may not qualify if:

• Prior treatment with leflunomide
• Patients who are pomalidomide refractory, defined as subjects who progress on or within 60 days of pomalidomide when given as a single agent or in combinatorial therapies. Prior exposure to pomalidomide without refractoriness is allowed
• Current or planned use of other anti-myeloma therapies besides leflunomide, pomalidomide, and dexamethasone
• Current or planned growth factor or transfusion support until after initiation of treatment
• Prior allogeneic transplant
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents
• Positive for tuberculosis or latent tuberculosis (TB)
• Positive for hepatitis A, B, or C
• Known human immunodeficiency virus (HIV) infection
• Prior diagnosis of rheumatoid arthritis
• Acute active infection requiring systemic therapy within 2 weeks prior to enrollment
• Subject has history of anaphylaxis to thalidomide, lenalidomide, pomalidomide, cholestyramine or dexamethasone
• Non-hematologic malignancies within the past 3 years, with the exceptions of
• Adequately treated basal cell or squamous cell skin cancer,
• Carcinoma in situ of the cervix,

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (8)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

City of Hope at Seacliff

Huntington Beach, California, 92648, United States

RECRUITING

City of Hope at Antelope Valley

Lancaster, California, 93534, United States

RECRUITING

City of Hope at Long Beach Elm

Long Beach, California, 90813, United States

RECRUITING

City of Hope at Newport Beach Fashion Island

Newport Beach, California, 92660, United States

RECRUITING

City of Hope at South Pasadena

South Pasadena, California, 91030, United States

RECRUITING

City of Hope at South Bay

Torrance, California, 90503, United States

RECRUITING

City of Hope at Upland

Upland, California, 91786, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Leflunomide; pomalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Michael A Rosenzweig

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2020
• First Posted: August 11, 2020
• Study Start: November 27, 2020
• Primary Completion (Estimated): February 14, 2027
• Study Completion (Estimated): February 14, 2027
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

US (8)