Leflunomide and Steroids for Acute Graft-versus-Host Disease
This study is testing the safety and side effects of combining leflunomide with steroids to treat acute graft-versus-host disease (GvHD) in patients who have had a stem cell transplant for blood cancers. GvHD happens when the new donor cells attack your body's healthy cells. Both leflunomide and steroids are drugs that help calm down your immune system. Researchers hope that using them together will better treat GvHD. This trial aims to see how well patients tolerate this combination and if it helps reduce GvHD. The study is looking for about 18 adult participants who have acute GvHD and are at least 18 years old. The current status of the study is unclear.
- Study design
- This is an interventional study, meaning participants will receive specific treatments. It plans to enroll about 18 participants.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- The study will track adverse events for up to 6 months. Other outcomes, like overall survival and progression-free survival, will be assessed at one year.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT05443425
Leflunomide in Combination With Steroids for the Treatment of Acute Graft-versus-Host Disease After Donor Stem Cell Transplant for Hematologic Malignancies
Recruiting
PHASE1Ages 18+InterventionalTreatmentCity of Hope Medical CenterInvestigator-initiated
~18 participants
Updated 2026-07-08 on ClinicalTrials.gov
What's tested:CholestyramineLeflunomideSteroid Therapy
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Incidence of adverse events
Measured over Up to 6 months
Conditions
Where it's being run
1 sites across 1 statesCalifornia1
Study leadership
- Monzr M. Al Malki · PRINCIPAL_INVESTIGATOR · City of Hope Medical Center
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
Age \>= 18 years old
Karnofsky performance status \>= 70
Clinically suspected grade II-IV aGvHD based on Mount Sinai Acute GVHD International Consortium (MAGIC) Consensus criteria occurring after allogeneic hematopoietic cell transplantation (HCT) and GvHD prophylaxis regimen. Grade I acute (a)GvHD requiring systemic steroids is allowed. Clinical suspicion of aGvHD by the treating physician is sufficient, provided that alternative diagnosis of drug effects or infection are adequately ruled out
Note: HCT from any donor (related or unrelated with any degree of human leukocyte antigen \[HLA\] matching) and any graft source (bone marrow, peripheral blood stem cells, or cord blood) for hematologic malignancy or disorder. Recipient of myeloablative and reduced-intensity conditioning regimens are eligible
Biopsy of acute GvHD target organ is recommended but not required. Enrollment should not be delayed for biopsy or pathology results. Patients who do not enroll within 72 hours from start of steroids are not permitted to participate
Evidence of myeloid engraftment (e.g., absolute neutrophil count \[ANC\] \>= 0.5 x 10\^9/L for 3 consecutive days if ablative therapy was previously used). Use of growth factor supplementation is allowed
No prior systemic treatment for treatment of acute GvHD except for a maximum of 72 hours of prednisone =\< 2 mg/kg/day (or intravenous \[IV\] methylprednisone equivalent). Topical skin steroid treatment and non-absorbable oral steroid treatment for GI GvHD are permissible
Patients should be able to swallow and retain oral medication
Total bilirubin =\< 2 X ULN (unless has Gilbert's disease or aGvHD within 3 days of enrollment) (performed within 14 days prior to day 1 of protocol therapy)
Aspartate aminotransferase (AST) =\< 3 x upper limit of normal (ULN) (performed within 14 days prior to day 1 of protocol therapy)
Alanine aminotransferase (ALT) =\< 3 x ULN (performed within 14 days prior to day 1 of protocol therapy)
Creatinine clearance of \>= 50 mL/min per 24-hour urine test or the Cockcroft-Gault formula (performed within 14 days prior to day 1 of protocol therapy)
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 3 months 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
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)
What this trial measures
- Incidence of adverse eventsUp to 6 months
Toxicity will be graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events version 5.0. Unacceptable toxicity (UT) evaluation period will be from starting first loading dose of leflunomide to occurrence of UTs, or stopping leflunomide due to graft versus host disease (GVHD) progression, or day +28, whichever comes first.