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

• Status: Completed
• Trial end date: 2012-04-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: David Miklos; Stanford University
• Collaborator: Novartis
• Treatments: Imatinib Mesylate

Criteria

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.