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

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.