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Acute Graft Versus Host DiseasePhase 1NCT05443425

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

A Phase 1 study testing Cholestyramine, Leflunomide and Steroid Therapy in people with Acute Graft Versus Host Disease and Hematopoietic and Lymphoid System Neoplasm, run by City of Hope Medical Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cholestyramine, Leflunomide and Steroid Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
16 Jun 2023to 5 Jan 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
  • Age >= 18 years old
  • Karnofsky performance status >= 70
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  • 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)

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site, 1 recruiting

  • City of Hope Medical Center

    Duarte, California, 91010

    Monzr M. Al Malki, 626-214-2405, malmalki@coh.org

    Monzr M. Al Malki

    Recruiting

Other trials in United States

About this study

Official title: Pilot Trial of Leflunomide in Combination With Steroids for the Treatment of Acute Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Assess the safety and tolerability of leflunomide administration in transplant patients with diagnosis of acute graft-versus-host disease (GvHD) requiring systemic therapy, by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration.

SECONDARY OBJECTIVES:

  1. Obtain preliminary evidence of leflunomide activity against acute GvHD by estimating the overall response rate (ORR).

II. Obtain estimates of total steroid dose and length of therapy (area under curve).

III. Day +180 non-relapse mortality (NRM). IV. Overall survival (OS) and progression-free survival (PFS) at one-year. V. Rate and severity of infections during leflunomide administration.

EXPLORATORY OBJECTIVES:

  1. Assess the clinical pharmacokinetics of teriflunomide (active metabolite of leflunomide).

II. Assess the presence of and percentage of immune cell subsets (including but not limited to Th17 and regulatory T cells) in blood during leflunomide administration.

III. Assess the changes in presence and levels of GvHD biomarkers and inflammatory cytokines in plasma during the course of treatment with leflunomide.

IV. Obtain a preliminary estimate of gut microbiome diversity at baseline (preferably before leflunomide administration), and then on days +14, +28, and +56.

OUTLINE:

Patients receive steroid therapy at the discretion of the treating physician. Beginning within 3 days of starting steroids, patients receive leflunomide orally (PO) once daily (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.

After completion of study treatment, patients are followed up at 28 days, 56 days, 100 days, and 6 months from last dose of leflunomide.

Being tested
Cholestyramine, Leflunomide, Steroid Therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CholestyramineDrug

    Also called Cholybar, Colestyramine, Duolite AP143 Resin, Questran

    Given PO

  • LeflunomideDrug

    Also called Arava, SU101

    Given PO

  • Steroid TherapyDrug

    Given steroid therapy

Study groups in NCT05443425
Study groupRoleWhat they receive
Treatment of aGVHD (steroid therapy, leflunomide)ExperimentalPatients 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.
Receives: Drug: Cholestyramine; Drug: Leflunomide; Drug: Steroid Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 6 months

Secondary outcomes (8)

  1. Overall response rate

    Patients who have partial or complete response will be counted as responders. Patients who have stable or progressive disease or withdraw the study early before response assessment is completed will be counted as non-responders.

    Measured: At 28 days

  2. Total steroids and length of therapy

    Area under curve will be recorded.

    Measured: Up to 6 months

  3. Non-relapse mortality (NRM)

    Will be calculated from day 0 to date of non-disease death from causes other than relapse or progression. Disease relapse/progression will be counted as a competing risk. NRM will be censored at the last follow-up date if patients are alive and free of disease relapse/progression.

    Measured: At day 180

  4. Failure-free survival (FFS)

    FFS will be censored on the last follow-up if patient is still alive and free of any event of interest.

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

  5. Overall survival (OS)

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

  6. Progression-free survival (PFS)

    PFS will be censored on the last disease assessment date if patient is still alive and disease relapse/progression is not observed.

    Measured: From day 0 to date of disease relapse/progression, or death regardless of cause, whichever comes first, assessed up to 1 year

  7. Incidence of bloodstream infections

    The rate of bloodstream infections will be evaluated during leflunomide administration.

    Measured: Up to 6 months

  8. Incidence of bloodstream infection severity

    The severity of infections will be evaluated during leflunomide administration.

    Measured: Up to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jul 2022
  2. Study start16 Jun 2023
  3. Primary completion5 Jan 2027 (estimated)
  4. Study completion5 Jan 2027 (estimated)

Resources

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 (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05443425
Sponsor's protocol ID
22026
Other IDs
NCI-2022-05061, 22026, P30CA033572
Status last verified
Jul 2026
First submitted
28 Jun 2022
Last updated
8 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cholestyramine, Leflunomide and Steroid Therapy in people with Acute Graft Versus Host Disease and Hematopoietic and Lymphoid System Neoplasm, 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 20 inclusion and 26 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: looking for participants now, as of the sponsor's last update on 8 Jul 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?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (time frame: Up to 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05443425.

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 8 Jul 2026.

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