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.

Condition	Treatment or Intervention	Phase
Graft Versus Host Disease	Drug: fludarabine	Phase I Phase II

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated dose, toxicity, and efficacy of fludarabine in patients with steroid resistant chronic graft versus host disease.

PROTOCOL 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.

Criteria

PROTOCOL ENTRY CRITERIA:

--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

--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)

--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

Study chairs or principal investigators

Christos E. Emmanouilides,  Study Chair,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000067435; UCLA-9701029; NCI-G99-1650
Record last reviewed:  September 2004
Last Updated:  October 13, 2004
Record first received:  January 21, 2000
ClinicalTrials.gov Identifier:  NCT00004194
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08