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

NCT04212416 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 19202NCI-2019-04532
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects of leflunomide in treating patients with steroid dependent chronic graft versus host disease (cGVHD). cGVHD is a common complication of bone marrow transplant. GVHD occurs when immune cells transplanted from a donor (the graft) recognize the transplant recipient (the host) as foreign, and cause damage to the skin, gastrointestinal tract or other organs. Steroids are the first line of therapy and benefits are seen in about one-third of patients with cGVHD. Prolonged use of steroids is associated with multiple complications. Leflunomide may decrease the body's immune response and reduce inflammation associated with cGVHD.

Conditions

Chronic Graft Versus Host Disease; Steroid Refractory Graft Versus Host Disease

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity

  Toxicity will be graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v.5.0).

  Up to 28 days

Secondary Outcomes (9)

• Leflunomide activity

  At 24 weeks

• Changes in cGVHD severity

  Baseline up to 30 days post treatment

• Changes in symptom activity

  Baseline up to 30 days post treatment

• Failure-free survival

  At 24 weeks

• Failure-free survival

  At 28 days follow-up

Other Outcomes (3)

• Presence and levels of immune cells (i.e., T and B cells, regulatory T cells [T regs], T cell receptor excision circles [TRECs]) after leflunomide consumption

  Up to 28 days follow-up

• Effect of leflunomide consumption of the presence and levels of GVHD inflammatory biomarkers

  Up to 48 weeks

• Pharmacokinetics concentration of teriflunomide in patients with chronic GVHD

  Up to 28 days follow-up

Study Arms (1)

Treatment (leflunomide)

EXPERIMENTAL

Patients receive leflunomide PO QD for days 1-28. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may optionally continue leflunomide for an additional 6 cycles as long as response or stable disease is maintained.

Drug: Leflunomide

Interventions

Leflunomide DRUG

Given PO

Also known as: Arava, SU101

Treatment (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.
• 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.

You may not qualify if:

• Exposure to any new immunosuppressive medication in the 4 weeks prior to enrollment.
• Donor lymphocyte infusion within 100 days prior to enrollment.
• Patients may not be receiving any other investigational agents concurrently. Oral chemotherapeutic agents or biologics -for example ruxolitinib or rituximab therapy and ibrutinib / imatinib (either past or current exposure) - is allowed.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent.
• Active infection requiring antibiotics. 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.
• Uncontrolled cardiac angina or symptomatic congestive heart failure (New York Heart Association \[NYHA\] class III or IV).
• Pregnant women are excluded from this study. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with leflunomide.
• Patients should not have any uncontrolled illness including ongoing or active infection.
• Active malignant relapse.
• Patients with other active malignancies are ineligible for this study, other than superficial localized skin cancer (basal or squamous cell carcinoma).
• Active diarrhea, not related to cGVHD.
• Clinically significant uncontrolled illness.
• Patients on dialysis.
• Patients requiring ventilator support.
• Patients with acute GvHD

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

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

Leflunomide

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Amandeep Salhotra

  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: July 17, 2019
• First Posted: December 27, 2019
• Study Start: May 12, 2020
• Primary Completion (Estimated): June 22, 2026
• Study Completion (Estimated): June 22, 2026
• Last Updated: July 4, 2025

Record last verified: 2025-07

Locations

US (1)