Leflunomide in Combination With Steroids for the Treatment of Acute Graft-versus-Host Disease After Donor Stem Cell Transplant for Hematologic Malignancies

Exclusion Criteria

• •Recipient of more than one allogeneic HCT
• •Received more than 3 days of systemic corticosteroid for treatment of aGvHD
• •Presence of GVHD overlap syndrome
• •Prior treatment with leflunomide
• •Current or planned use of other investigational agents, or concurrent biological, chemotherapy, or radiation therapy during the study treatment period
• •Use of other drugs for treatment of acute GvHD
• •History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent (leflunomide or cholestyramine)
• •Clinically significant uncontrolled illness
• •Patients on dialysis
• •Patient requiring ventilator support
• •Presence of an active uncontrolled infection. An active uncontrolled infection is defined as hemodynamic instability attributed to sepsis or new symptoms, worsening physical signs, or radiographic findings attributable to infection. Persisting fever without signs or symptoms will not be interpreted as an active uncontrolled infection
• •Known history of immunodeficiency virus (HIV) infection
• •Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection that requires treatment, HBV deoxyribonucleic acid (DNA) and HCV ribonucleic acid (RNA) must be undetectable upon testing. Prior test results obtained as part of standard of care that confirm a subject is immune and not at risk for reactivation (i.e., hepatitis B surface antigen negative, surface antibody positive) may be used for purpose of eligibility and test do not need to be repeated. Subjects within prior positive serology results must have negative polymerase chain reaction results. Subjects whose immune status is unknown must have results confirming immune status before enrolment
• •Subjects with evidence of relapsed primary disease, or subjects who have been treated for relapse after the allogeneic (allo)-HCT was performed
• •Severe organ dysfunction unrelated to underlying GvHD, including:
• •* Cholestatic disorders or unresolved veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to GvHD and ongoing organ dysfunction)
• •* Clinically significant uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months of enrollment, New York Heart Association Class III or IV congestive heart failure, circulatory collapse requiring vasopressor or inotropic support, or arrhythmia that requires therapy
• •* Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen
• •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
• •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. e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc.
• •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)