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

NCT05443425 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 22026NCI-2022-05061P30CA033572
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the safety and side effects of leflunomide in combination with steroids in treating patients with acute graft versus host disease who have undergone done stem cell transplant for blood cancers (hematologic malignancies). Sometimes the transplanted cells from a donor can attack the body's normal cells (called graft-versus-host disease). Leflunomide and steroids are immunosuppressive drugs that work in different ways to lower the body's immune response so that the new donor immune cells do not attack the body's normal cells. Giving leflunomide in combination with steroids may help treat acute graft versus host disease in patients after stem cell transplant for hematologic malignancies.

Conditions

Acute Graft Versus Host Disease; Hematopoietic and Lymphoid System Neoplasm

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events

  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.

  Up to 6 months

Secondary Outcomes (8)

• Overall response rate

  At 28 days

• Total steroids and length of therapy

  Up to 6 months

• Non-relapse mortality (NRM)

  At day 180

• Failure-free survival (FFS)

  From day 0 to GVHD progression, disease relapse, starting new GVHD therapy, death regardless of cause, whichever comes first, assessed up to 6 months

• Overall survival (OS)

  From day 0 to date of death regardless of cause, assessed up to 1 year

Study Arms (1)

Treatment of aGVHD (steroid therapy, leflunomide)

EXPERIMENTAL

Patients receive steroid therapy at the discretion of the treating physician. Beginning within 3 days of starting steroids, patients receive leflunomide PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity. Patients who respond to leflunomide treatment will be tapered off from day 29 until day 56.

Drug: Cholestyramine; Drug: Leflunomide; Drug: Steroid Therapy

Interventions

Cholestyramine DRUG

Given PO

Also known as: Cholybar, Colestyramine, Duolite AP143 Resin, Questran, Questran Light

Treatment of aGVHD (steroid therapy, leflunomide)

Leflunomide DRUG

Given PO

Also known as: Arava, SU101

Treatment of aGVHD (steroid therapy, leflunomide)

Steroid Therapy DRUG

Given steroid therapy

Treatment of aGVHD (steroid therapy, leflunomide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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:

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Interventions

Cholestyramine Resin; Leflunomide

Intervention Hierarchy (Ancestors)

Polystyrenes; Plastics; Polymers; Macromolecular Substances; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Monzr M. Al Malki

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2022
• First Posted: July 5, 2022
• Study Start: June 16, 2023
• Primary Completion (Estimated): January 5, 2027
• Study Completion (Estimated): January 5, 2027
• Last Updated: July 4, 2025

Record last verified: 2025-07

Locations

US (1)