A Pilot Study of Imatinib Mesylate in Steroid Refractory Chronic Graft Versus Host Disease

To determine if subjects with steroid refractory cGVHD can tolerate imatinib mesylate and whether their cGVHD responds to imatinib mesylate.

Study Overview

• Status: Completed
• Conditions: Graft vs Host Disease
• Intervention / Treatment: Drug: Imatinib

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center (FHCRC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA

• Chronic graft-vs-host disease (cGVHD) requiring systemic therapy occurring > 100 days after hematopoietic cell transplant with either:

  1. Persistent steroid dependence defined as the inability to taper steroid treatment to less than 0.25 mg/kg/d prednisone or its equivalent for at least 3 months.
  2. Progression of cGVHD signs and symptoms on steroid therapy equivalent to prednisone 0.5 mg/kg/d for at least 1 month.

• At least one of the following manifestations:

  1. Skin changes (rash, sclerosis, fasciitis, or ulceration).
  2. Abnormal eye wetness ≤ 5 mm as measured by Schirmer's test.
  3. Oral mucosal changes (erythema, lichenoid changes, ulcers, or mucoceles).
  4. Thrombocytopenia (platelets < 50,000/uL).
  5. Abnormal liver function testing defined as alkaline phosphatase, AST, ALT, or total bilirubin > upper limit of normal (ULN).
  6. Bronchiolitis obliterans (diagnosed by a > 5% annual decline in FEV1 with the lowest post-transplant FEV1/FVC < 0.8 and an appropriate CT scan or lung biopsy).
• Has been on a fixed dose of steroids or a fixed dose of steroids and one other immunosuppressant (cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, or extracorporeal photopheresis) for ≥ 30 days before starting imatinib.
• Life expectancy ≥ 6 months.
• Ability to understand and willingness to sign a written informed consent document.
• Karnofsky performance status ≥ 3 50% (Appendix B).
• At least 18 years of age.
• If a female of reproductive potential (defined as having at least 1 menstrual period in the past 12 months), must have a negative pregnancy test performed ≤ 7 days before starting study drug.
• If a female of reproductive potential, agrees to use contraception for the duration of the trial.
• Total bilirubin < 1.5X ULN.
• Aspartate transaminase (AST) < 2.5 x ULN.
• Alanine aminotransferase (ALT) < 2.5 x ULN.
• Alkaline phosphatase < 2.5 x ULN.
• Absolute neutrophil count (ANC) > 500/uL (growth factor supplementation is allowed).
• Hematocrit > 26% (transfusion support is allowed).
• Platelet count > 20,000/uL.

EXCLUSION CRITERIA

• Received another investigational agent ≤ 30 days before starting the study drug.
• Ongoing intercurrent illness such as an infection not responsive to antibiotics, antiviral medicines, or antifungal medicines.
• Progressive malignant disease.
• Secondary malignancy that has not been effectively treated within the past 5 years (except localized basal cell or squamous cell carcinoma).
• Imatinib intolerance or allergy.
• Participant is breast-feeding.
• Not willing to comply with treatment or response evaluation.
• Received an allogeneic cell product [including donor lymphocyte infusion (DLI) or hematopoietic cell boost] ≤ 100 days before starting study drug.
• Steroid and/or immunosuppressant dose has changed ≤ 30 days before starting study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Imatinib; 200 mg orally daily and 400 mg orally daily for 4 weeks.	Drug: Imatinib; The single cohort for this study will receive 2 dose levels of imatinib, 200 mg orally daily followed by 400 mg orally daily.; Other Names: Gleevec

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The frequency of adverse events graded according to the CTCAE will be the primary endpoint	Subjects will be monitored at 1, 4, 8, 16, and 24 weeks.

Collaborators and Investigators

• Sponsor: David Miklos
• Collaborators: Novartis
• Investigators: Principal Investigator: David Miklos, MD, Stanford University

Publications and helpful links

General Publications

• Chen GL, Arai S, Flowers ME, Otani JM, Qiu J, Cheng EC, McMillan A, Johnston LJ, Shizuru JA, Miklos DB. A phase 1 study of imatinib for corticosteroid-dependent/refractory chronic graft-versus-host disease: response does not correlate with anti-PDGFRA antibodies. Blood. 2011 Oct 13;118(15):4070-8. doi: 10.1182/blood-2011-03-341693. Epub 2011 Aug 9.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (ACTUAL): April 1, 2012
• Study Completion (ACTUAL): April 1, 2012

Study Registration Dates

• First Submitted: September 25, 2008
• First Submitted That Met QC Criteria: September 25, 2008
• First Posted (ESTIMATE): September 26, 2008

Study Record Updates

• Last Update Posted (ACTUAL): April 15, 2020
• Last Update Submitted That Met QC Criteria: April 13, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Imatinib Mesylate
• Other Study ID Numbers: IRB-14821; 14821 (OTHER: Stanford University Alternate IRB Approval Number); BMT195 (OTHER: OnCore Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No