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

Launched by CITY OF HOPE MEDICAL CENTER · Aug 8, 2020

Keywords

ClinConnect Summary

This clinical trial is looking at a new treatment combination for patients with multiple myeloma, a type of blood cancer that can come back after treatment or does not respond to existing therapies. The study will test whether using three medications—leflunomide, pomalidomide, and dexamethasone—together is more effective than using pomalidomide and dexamethasone alone. Leflunomide may help stop cancer cells from growing, while pomalidomide can boost the body’s immune response against the cancer, and dexamethasone is a chemotherapy drug that helps kill cancer cells.

To participate in this trial, individuals need to be between the ages of 65 and 74, have measurable multiple myeloma that has returned or not responded to at least one prior treatment, and have a life expectancy of more than three months. They should also be healthy enough to tolerate the treatments. Participants can expect close monitoring by healthcare professionals throughout the trial, and they will need to agree to use effective birth control if they are of childbearing age. This trial is currently recruiting participants, and it aims to provide more options for those battling multiple myeloma.

Gender

ALL

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)