Chronic Graft Versus Host DiseasePhase 1NCT04212416
Leflunomide in Treating Patients With Steroid Dependent Chronic Graft Versus Host Disease
A Phase 1 study testing Leflunomide in people with Chronic Graft Versus Host Disease and Steroid Refractory Graft Versus Host Disease, run by City of Hope Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Graft Versus Host Disease, Steroid Refractory Graft Versus Host Disease
- What is being tested?
- Leflunomide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Sep 2020to 17 Jun 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- 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).
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- 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
- Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection.
- 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.
- Inability to comply with protocol therapy and follow up visits.
- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
City of Hope Medical Center
Duarte, California, 91010
About this study
Official title: A Safety and Feasibility Trial of Leflunomide in Patients With Steroid Dependent Chronic Graft-Versus-Host Disease
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.
Read the detailed description
PRIMARY OBJECTIVE:
- Evaluate safety and tolerability of leflunomide in hematopoietic cell transplant (HCT) patients with steroid dependent chronic GvHD (cGvHD).
SECONDARY OBJECTIVES:
- Characterize the toxicity profile of leflunomide in patients with steroid dependent cGVHD.
II. Obtain preliminary evidence of leflunomide activity against GVHD by estimating the response rate (as defined by 2014 National Institutes of Health [NIH] consensus development project on clinical trials in cGVHD) in an expansion cohort of 12 patients with steroid dependent cGVHD.
III. Evaluate changes in cGVHD severity using physician-reported cGVHD activity assessment form.
IV. Evaluate changes in symptom activity using cGVHD activity assessment patient self-report.
- Evaluate failure-free survival and GVHD free survival. VI. Evaluate changes in steroid doses while on therapy. VII. Evaluate rate of infectious complications during leflunomide administration.
EXPLORATORY OBJECTIVES:
- Assess the presence and percentage of immune cell subsets (including but not limited to Th17 and Treg cells) in whole blood after leflunomide administration.
II. Assess the changes in the presence and levels of GVHD inflammatory biomarkers and cytokines (including but not limited to IL-17A, IL-21, and IL-2) in plasma after leflunomide administration.
III. Assess the plasma pharmacokinetics of teriflunomide (active metabolite of leflunomide).
OUTLINE:
Patients receive leflunomide orally (PO) once daily (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.
After completion of study treatment, patients are followed up at 30 days, and then periodically thereafter.
- Being tested
- Leflunomide
- Medical subject headings
- Bronchiolitis Obliterans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LeflunomideDrug
Also called Arava, SU101
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Leflunomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to 28 days
Secondary outcomes (9)
Leflunomide activity
Leflunomide activity in patients with steroid dependent chronic graft versus host disease (cGVHD) and disease status at 24 weeks in terms of partial and complete response will be evaluated as defined by 2014 National Institutes of Health (NIH) consensus development project on clinical trials in cGVHD.
Measured: At 24 weeks
Changes in cGVHD severity
Evaluated using physicians-reported cGVHD activity assessment form.
Measured: Baseline up to 30 days post treatment
Changes in symptom activity
Evaluated using cGVHD activity assessment patient self-report.
Measured: Baseline up to 30 days post treatment
Failure-free survival
Defined by the absence of second line of GVHD treatment, non-relapse mortality, and recurrent malignancy during leflunomide treatment. Failure free survival estimates will be calculated using the Kaplan-Meier method.
Measured: At 24 weeks
Failure-free survival
Defined by the absence of second line of GVHD treatment, non-relapse mortality, and recurrent malignancy during leflunomide treatment. Failure free survival estimates will be calculated using the Kaplan-Meier method.
Measured: At 28 days follow-up
GVHD-free survival
Defined as the probability of being alive without clinically significant GvHD at any time-point post transplantation.
Measured: At 24 weeks
GVHD-free survival
Defined as the probability of being alive without clinically significant GvHD at any time-point post transplantation.
Measured: At 28 days follow-up
Changes in steroid doses while on therapy
Will be recorded and assessed at each study visit time-points.
Measured: Baseline up to 48 weeks
Rate of infectious complications
Will be evaluated while on therapy.
Measured: Up to 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2019
- Study start14 Sep 2020
- Primary completion17 Jun 2027 (estimated)
- Study completion17 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Amandeep Salhotra, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04212416
- Sponsor's protocol ID
- 19202
- Other IDs
- NCI-2019-04532, 19202
- Status last verified
- Oct 2026
- First submitted
- 17 Jul 2019
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety and Feasibility Trial of Leflunomide in Patients With Steroid Dependent Chronic Graft-Versus-Host Disease
- ClinicalTrials.gov ID
- NCT04212416
- Acronym / sponsor ID
- 19202
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 18 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 14 Sep 2020 (actual)
- Primary completion
- 17 Jun 2027 (estimated)
- Study completion
- 17 Jun 2027 (estimated)
- First posted
- 27 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- Evaluate safety and tolerability of leflunomide in hematopoietic cell transplant (HCT) patients with steroid dependent chronic GvHD (cGvHD).
SECONDARY OBJECTIVES:
- Characterize the toxicity profile of leflunomide in patients with steroid dependent cGVHD.
II. Obtain preliminary evidence of leflunomide activity against GVHD by estimating the response rate (as defined by 2014 National Institutes of Health [NIH] consensus development project on clinical trials in cGVHD) in an expansion cohort of 12 patients with steroid dependent cGVHD.
III. Evaluate changes in cGVHD severity using physician-reported cGVHD activity assessment form.
IV. Evaluate changes in symptom activity using cGVHD activity assessment patient self-report.
- Evaluate failure-free survival and GVHD free survival. VI. Evaluate changes in steroid doses while on therapy. VII. Evaluate rate of infectious complications during leflunomide administration.
EXPLORATORY OBJECTIVES:
- Assess the presence and percentage of immune cell subsets (including but not limited to Th17 and Treg cells) in whole blood after leflunomide administration.
II. Assess the changes in the presence and levels of GVHD inflammatory biomarkers and cytokines (including but not limited to IL-17A, IL-21, and IL-2) in plasma after leflunomide administration.
III. Assess the plasma pharmacokinetics of teriflunomide (active metabolite of leflunomide).
OUTLINE:
Patients receive leflunomide orally (PO) once daily (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.
After completion of study treatment, patients are followed up at 30 days, and then periodically thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (leflunomide) | Experimental | Drug: LeflunomidePatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Documented informed consent of the participant and/or legally authorized representative.
- Agreement to allow the use of archival tissue from diagnostic tumor biopsies.
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LeflunomideAlso: Arava, SU101Given PO | Drug | Treatment (leflunomide) |
Primary outcome
Dose limiting toxicity
Time frame: Up to 28 days
Toxicity will be graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v.5.0).
9 secondary outcomes
Leflunomide activity
Time frame: At 24 weeks
Changes in cGVHD severity
Time frame: Baseline up to 30 days post treatment
Changes in symptom activity
Time frame: Baseline up to 30 days post treatment
Failure-free survival
Time frame: At 24 weeks
Failure-free survival
Time frame: At 28 days follow-up
GVHD-free survival
Time frame: At 24 weeks
GVHD-free survival
Time frame: At 28 days follow-up
Changes in steroid doses while on therapy
Time frame: Baseline up to 48 weeks
Rate of infectious complications
Time frame: Up to 48 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amandeep Salhotra principal investigator
City of Hope Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Leflunomide in people with Chronic Graft Versus Host Disease and Steroid Refractory Graft Versus Host Disease, run by City of Hope Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicity (time frame: Up to 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2026.