Combination treatment for relapsed or refractory multiple myeloma

A Phase 2 Trial of Leflunomide, Pomalidomide, and Dexamethasone for Relapsed/Refractory Multiple Myeloma

This study is testing a new combination of three medications to see if it can help people with relapsed or refractory multiple myeloma feel better and improve their treatment outcomes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 29 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: City of Hope Medical Center (Academic / other)
• Drugs / interventions: Chemotherapy, Immunotherapy
• Locations: 8 sites (Duarte, California and 7 other locations)
• Trial ID: NCT04508790 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the effectiveness of a combination of leflunomide, pomalidomide, and dexamethasone in treating patients with relapsed or refractory multiple myeloma. The study aims to estimate the response rate and evaluate the antitumor activity of this three-drug regimen. Patients will receive leflunomide orally for 28 days, pomalidomide for 21 days, and dexamethasone on specific days within a 28-day cycle. The trial will also assess the safety and toxicity of the treatment, as well as the duration and depth of response.

Who should consider this trial

Good fit: Ideal candidates include adults diagnosed with relapsed or refractory multiple myeloma who have measurable disease and an ECOG performance status of 2 or less.

Not a fit: Patients with non-measurable disease or those with a life expectancy of less than three months may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with difficult-to-treat multiple myeloma.

How similar studies have performed: While this approach combines established therapies, the specific combination of leflunomide with pomalidomide and dexamethasone is relatively novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

* 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
* Platelets \>= 75.0 x 10\^9/L (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)

  * NOTE: Screening platelet count should be independent of platelet transfusions for at least 2 weeks
* Hemoglobin \>= 8.0 g/dL (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)

  * NOTE: Transfusion support is allowed
* Total bilirubin =\< 2 X upper limit of normal (ULN) (unless has Gilbert's disease) (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
* Aspartate aminotransferase (AST) =\< 3.5 x ULN (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
* Alanine aminotransferase (ALT) =\< 3.5 x ULN (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
* Alkaline phosphatase \< 5 x ULN (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
* Creatinine clearance of \>= 30 mL/min per 24 hour urine test (performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
* Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

  * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 4 weeks after the last dose of protocol therapy

  * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)

Exclusion Criteria:

* 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,
  * Prostate cancer \< Gleason grade 6 with stable prostate specific antigen (PSA), or
  * Successfully treated in situ carcinoma of the breast
* Females only: Pregnant or breastfeeding
* Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Where this trial is running

Duarte, California and 7 other locations

• City of Hope Medical Center — Duarte, California, United States (Recruiting)
• City of Hope at Seacliff — Huntington Beach, California, United States (Recruiting)
• City of Hope at Antelope Valley — Lancaster, California, United States (Recruiting)
• City of Hope at Long Beach Elm — Long Beach, California, United States (Recruiting)
• City of Hope at Newport Beach Fashion Island — Newport Beach, California, United States (Recruiting)
• City of Hope at South Pasadena — South Pasadena, California, United States (Recruiting)
• City of Hope at South Bay — Torrance, California, United States (Recruiting)
• City of Hope at Upland — Upland, California, United States (Recruiting)

Study contacts

• Principal investigator: Michael A Rosenzweig — City of Hope Medical Center

Conditions Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma