Leflunomide in Treating Patients With Steroid Dependent Chronic Graft Versus Host Disease

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.
• •Karnofsky performance status of \>= 70 %.
• •Ability to read and understand English or Spanish for questionnaires.
• •Recipients of allogeneic stem cell transplantation (sibling/unrelated/umbilical cord blood \[UCB\]/Haplo) with myeloablative or non-myeloablative conditioning regimens.
• •Participants must have steroid-dependent cGVHD. Steroid dependent cGVHD is defined as having persistent signs and symptoms of cGVHD despite the use of prednisone for 2 months without complete resolution of signs and symptoms. Both classic cGVHD and overlap syndromes will be allowed to participate.
• •Estimated life expectancy greater than 3 months.
• •No more than 4 prior lines of treatment. Sirolimus and tacrolimus used for prophylaxis will not be counted as line of therapy.
• •Stable dose of corticosteroids for 2 weeks prior to enrollment.
• •Able to swallow pills.
• •Absolute neutrophil count (ANC) \>= 1,000/mm\^3 (without myeloid growth factors within 1 week of study entry) (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated).
• •Platelets \>= 50,000/mm\^3 (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated).
• •* NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement.
• •Total bilirubin =\< 2 mg/dl (exception permitted in patients with Gilbert's syndrome; aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2 x upper limit of normal \[ULN\]), unless hepatic dysfunction is a manifestation of presumed cGVHD (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated).
• •* Abnormal liver function tests (LFTs) (liver function panel) in the context of active cGVHD involving other organ systems may also be permitted if the treating physician documents the abnormal LFTs as being consistent with hepatic cGVHD and a liver biopsy will not be mandated in this situation.
• •AST =\< 2.0 x ULN (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated).
• •ALT =\< 2.0 x ULN (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated).
• •Creatinine clearance of \>= 60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal. or calculated by Cockcroft-Gault equation (performed within 28 days prior to day 1 of protocol therapy unless otherwise stated).
• •Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV)\*, active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin \[RPR\]) (performed within 28 days prior to day 1 of protocol therapy).
• •* If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed.
• •Meets other institutional and federal requirements for infectious disease titer requirements (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated).
• •* Note: Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy.
• •Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated).
• •* 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 3 months after the last dose of protocol therapy. The effects of study treatment on a developing fetus have the potential for teratogenic or abortifacient effects. Should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately.
• •* Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only).