Sirolimus as Secondary Therapy in Chronic Graft-Versus-Host Disease Not Responding To Prior Treatment

Fred Hutchinson Cancer Center (FHCC)

Status and phase: Completed; Phase 2

Conditions: Graft Versus Host Disease

Treatments: Drug: sirolimus

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00079183

1706.00

NCI-2011-01817 (Registry Identifier)

Details and patient eligibility

About

This phase II trial studies the side effects and how well sirolimus works as secondary therapy in treating patients with chronic graft-versus-host disease (GVHD) that did not respond to prior treatment. Sirolimus may be an effective treatment for chronic GVHD

Full description

PRIMARY OBJECTIVES:

I. To assess the safety of sirolimus administered at a dose which provides steady-state, whole blood trough levels of 5-10 ng/mL in patients with chronic GVHD.

II. To determine whether administration of sirolimus provides benefit for patients with chronic GVHD that has not responded adequately to previous systemic treatment.

OUTLINE:

Patients receive sirolimus orally (PO) once daily (QD). Patients continue to receive prednisone and cyclosporine or tacrolimus at the discretion of the managing physician.

After completion of study treatment, patients are followed up periodically.

Enrollment: 44 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

• Biopsy-confirmed diagnosis of clinical extensive chronic GVHD with inadequate response to previous treatment and where secondary systemic therapy is indicated because of

  • Clinical progression of signs and symptoms of chronic GVHD in a previously involved organ, or
  • Development of signs and symptoms of chronic GVHD in a previously uninvolved organ, or
  • Absence of improvement after 3 months of primary treatment, or
  • Continued need for treatment with prednisone at doses >= 1.0 mg/kg/day for more than 2 months, without qualification for type of donor, graft or conditioning regimen

• Patient or guardian able and willing to provide informed consent

• Stated willingness to use contraception in women of child-bearing potential (Food and Drug Administration [FDA] requirement)

• Stated willingness of the patient to comply with study procedures and reporting requirements

• Stated willingness of the physician most involved in management of chronic GVHD (the "managing physician,") to comply with study procedures and reporting requirements

Exclusion criteria

• Fungal or viral infection with no radiographic evidence of improvement during continued appropriate antimicrobial therapy
• Cytomegalovirus (CMV) antigenemia unresponsive to antiviral therapy
• Active disseminated varicella zoster virus (VZV) infection with persistent non-crusted lesions
• Inability to tolerate oral medications
• Absolute neutrophil count (ANC) < 1500/uL
• Platelet count < 50,000/uL
• Persistent or recurrent malignancy, including histopathologic evidence of myeloma or lymphoma; patients with breakpoint cluster region-abelson (bcr/abl) detected by polymerase chain reaction (PCR) assay as the only evidence of persistent chronic myeloid leukemia may be enrolled
• Pregnancy
• Known history of hypersensitivity to sirolimus

Trial design

Primary purpose: Supportive Care

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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44 participants in 1 patient group

Sirolimus

Experimental group

Description:

Study participants receive sirolimus added once daily to their baseline combination therapy of prednisone plus either cyclosporine or tacrolimus at the discretion of the managing physician. Treatment other than cyclosporine (or tacrolimus) and prednisone must be discontinued when administration of sirolimus is started. Topical therapy, including psoralen and UVA irradiation (PUVA), glucocorticoid creams, topical tacrolimus, oral beclomethasone, topical azathioprine and ophthalmic glucocorticoids may be given at the discretion of the managing physician in consultation with the transplant center.

Treatment:

Drug: sirolimus