Fludarabine in Treating Patients With Steroid-Resistant Chronic Graft- Versus-Host Disease
Fludarabine in Treating Patients With Steroid-Resistant Chronic Graft- Versus-Host Disease
RATIONALE: Fludarabine may be an effective treatment for graft-versus-host disease caused by
 bone marrow transplantation.

 PURPOSE: Phase I/II trial to study the effectiveness of fludarabine in treating patients who
 have chronic graft-versus-host disease that has not responded to steroid therapy.
OBJECTIVES: I. Determine the maximum tolerated dose, toxicity, and efficacy of fludarabine in
 patients with steroid resistant chronic graft versus host disease.

 OUTLINE: This is a dose escalation study. Phase I: Patients receive fludarabine IV over less
 than 30 minutes for 1-3 days. Treatment repeats every 4 weeks for up to 4 courses in the
 absence of relapse of underlying disease, malignancy, graft rejection, or unacceptable
 toxicity. Patients with progressive graft versus host disease after completion of 3 courses
 are taken off study. Patients with complete response are taken off study. Patients with
 partial response may continue treatment at the immediate prior dose level. Cohorts 3-6
 patients receive escalating doses of fludarabine until the maximum tolerated dose (MTD) is
 determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience
 dose limiting toxicity. Phase II: Patients receive fludarabine at the MTD from phase I of the
 study.

 PROJECTED ACCRUAL: A total of 15-27 patients will be accrued for this study.
DISEASE CHARACTERISTICS: Histologically or clinically proven chronic graft versus host
 disease (GVHD) that has failed to respond to at least 1 month of treatment with the
 following: Steroids (greater than 0.5 mg/kg/day) AND Cyclosporine or a cytotoxic agent
 (azathioprine or mercaptopurine) OR Other experimental treatment (such as chloroquine) All
 allogeneic bone marrow or peripheral blood stem cell transplantation patients eligible
 regardless of underlying disease for which transplantation was performed if: At least 45
 days since prior transplantation No relapse of underlying disease No loss of donor
 hematopoiesis Patients with a rapid deterioration of GVHD that is considered life
 threatening if not controlled are eligible after receiving high dose steroids (greater than
 1 mg/kg/day) for at least 10 days

 PATIENT CHARACTERISTICS: Age: Not specified Performance status: Not specified Life
 expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,300/mm3
 Platelet count at least 75,000/mm3 Hepatic: Not specified Renal: Creatinine no greater than
 2 mg/dL Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use
 effective contraception

 PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics Chemotherapy: No
 other concurrent cytotoxic drugs Endocrine therapy: Concurrent steroids allowed but must be
 tapered to less than 0.5 mg/kg/day of prednisone or equivalent prior to starting study drug
 (if symptomatic flare develops during taper, patients may continue on the lowest dose
 thought to produce stabilization) Radiotherapy: Not specified Surgery: Not specified Other:
 Concurrent cyclosporine and other nonmyelosuppressive drugs allowed No concurrent
 myelosuppressive agents (azathioprine, mercaptopurine)