RATIONALE: Sirolimus may be effective in treating chronic graft-versus-host disease that has not responded to previous systemic treatment.

PURPOSE: This phase II trial is studying how well sirolimus works as secondary therapy in treating patients with chronic graft-versus-host disease that has not responded to previous systemic treatment.

Condition	Treatment or Intervention	Phase
Graft Versus Host Disease	Drug: cyclosporine  Drug: prednisone  Drug: sirolimus  Drug: tacrolimus  Procedure: biological response modifier therapy  Procedure: graft versus host disease prophylaxis/therapy  Procedure: supportive care/therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the safety of sirolimus as secondary treatment for patients with chronic graft-versus-host disease who had an inadequate response to prior systemic treatment.
• Determine the efficacy of this drug in these patients.

OUTLINE: This is an open-label study.

Patients continue on oral prednisone and oral cyclosporine OR tacrolimus. Patients also receive oral sirolimus once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 39 patients will be accrued for this study within 3 years.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed chronic graft-versus-host disease (GVHD)
• Inadequate response to prior treatment
• Requires secondary systemic therapy as a result of 1 of the following:
• Clinical progression of signs and symptoms of chronic GVHD in a previously involved organ
• Development of signs or symptoms of chronic GVHD in a previously uninvolved organ
• No improvement after 3 months of primary treatment
• Continued need for at least 1.0 mg/kg/day of prednisone for more than 2 months without qualifying for type of donor, graft, or conditioning regimen
• No persistent or recurrent malignancy, including histologically confirmed myeloma or lymphoma
• Patients with bcr/abl detected by polymerase chain reaction assay as the only evidence of persistent chronic myeloid leukemia allowed

PATIENT CHARACTERISTICS: Age

• Any age

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 50,000/mm^3

Hepatic

• Not specified

Renal

• Not specified

Immunologic

• No fungal or viral infection without radiographic evidence of improvement during continued appropriate antimicrobial therapy
• No cytomegalovirus antigenemia unresponsive to antiviral therapy
• No active disseminated varicella-zoster viral infection with persistent non-crusted lesions

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to tolerate oral medicine
• No prior hypersensitivity to sirolimus

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• See Disease Characteristics
• Concurrent prednisone allowed

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No concurrent systemic immunosuppressive medications except cyclosporine or tacrolimus
• No concurrent grapefruit juice
• No concurrent ketoconazole or voriconazole
• No concurrent topical immunosuppressive treatment for chronic GVHD allowed

Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States; Recruiting

Study chairs or principal investigators

Paul Carpenter, MD,  Study Chair,  Fred Hutchinson Cancer Research Center   

Study ID Numbers:  CDR0000355110; FHCRC-1706.00
Record last reviewed:  April 2004
Last Updated:  March 10, 2005
Record first received:  March 8, 2004
ClinicalTrials.gov Identifier:  NCT00079183
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08