This phase I trial studies the side effects and best dose of leflunomide in treating
patients with multiple myeloma that has come back (recurrent) or has not responded to
previous treatment (refractory). Leflunomide may stop the growth of cancer cells by blocking
some of the enzymes needed for cell growth.
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Inclusion Criteria:
- All subjects must have the ability to understand and the willingness to sign a
written informed consent
- Patients must have a life expectancy of > 3 months
- Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status
of 0-2
- Patients must have a diagnosis of multiple myeloma
- Serum M-protein >= 0. 5 g/dL
- Urine M-protein >= 200 mg/24 hr
- Serum free light chain >=10 mg/dL provided the free light chain (FLC) ratio is
abnormal
- Patients must be refractory or relapsed after 2 prior regimens (induction therapy and
stem cell transplant +/- maintenance will be considered as one regimen)
- At least 2 weeks from prior therapy to time of start of treatment; prior therapy
includes steroids (except prednisone or equivalent - up to 10 mg per day is allowed)
- Platelet count >= 50,000/uL; platelet transfusions are not allowed within 14 days of
platelet assessment
- Absolute neutrophil count (ANC) >= 1000/mm^3; growth factor is not permitted within
14 days of neutrophil assessment
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2. 0 x ULN
- Calculated creatinine clearance (CrCl) >= 30 mL/min per 24 hour urine collection or
the Cockcroft-Gault formula
- Negative serum or urine beta-human chorionic gonadotropin (B-HCG) test (female
patient of childbearing potential* only), to be performed locally within the
screening period
- Negative for tuberculosis antigen (e. g. T-Spot test)
- Negative for hepatitis A, B, or C infection
- Adequate pulmonary function as defined by forced vital capacity (FVC) and carbon
monoxide diffusing capacity (DLCO) >= 50% of predicted by pulmonary function testing
- Agreement by females of childbearing potential* and sexually active males to use an
effective method of contraception (hormonal or barrier method of birth control or
abstinence) prior to study entry and for three months following duration of study
participation; should a woman become pregnant or suspect that she is pregnant while
participating on the trial, she should inform her treating physician immediately
- A female of childbearing potential is defined as a sexually mature woman who: 1)
has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been
naturally postmenopausal for at least 24 consecutive months
Exclusion Criteria:
- Prior treatment with leflunomide
- Current or planned use of other investigational agents, or concurrent biological,
chemotherapy, or radiation therapy during the study treatment period
- Current or planned growth factor or transfusion support until after initiation of
treatment; if growth factor or transfusion support is provided between screening and
start of treatment, the participant will no longer be eligible
- Prior diagnosis of rheumatoid arthritis
- Acute active infection requiring systemic therapy within 2 weeks prior to enrollment
- Pre-existing liver disease
- Known human immunodeficiency virus (HIV) infection
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to leflunomide or cholestyramine
- Non-hematologic malignancy within the past 3 years aside from the following
exceptions:
- Adequately treated basal cell or squamous cell skin cancer
- Carcinoma in situ of the cervix
- Prostate cancer < Gleason grade 6 with a stable prostate specific antigen (PSA)
- Successfully treated in situ carcinoma of the breast
- Clinically significant medical disease or condition that, in the investigator's
opinion, may interfere with protocol adherence or the patient's ability to give
informed consent
- Pregnant women and women who are lactating; breastfeeding should be discontinued if
the mother is enrolled on this study
- Any other condition that would, in the investigator's judgment, contraindicate the
patient's participation in the clinical study due to safety concerns or compliance
with clinical study procedures, e. g., infection/inflammation, intestinal obstruction,
unable to swallow medication, social/ psychological issues, etc
- NONCOMPLIANCE: 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)