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Sirolimus as Secondary Therapy in Treating Patients With Chronic Graft-Versus-Host Disease That Did Not Respond To Prior Treatment

This study has been completed.
National Cancer Institute (NCI)
Information provided by:
Fred Hutchinson Cancer Research Center Identifier:
First received: March 8, 2004
Last updated: March 13, 2012
Last verified: March 2012
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

Condition Intervention Phase
Graft Versus Host Disease
Drug: sirolimus
Other: questionnaire administration
Procedure: quality-of-life assessment
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: A Phase II Clinical Trial to Evaluate the Safety and Efficacy of Sirolimus for Secondary Treatment of Chronic Graft-versus-Host Disease

Resource links provided by NLM:

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Treatment success [ Time Frame: Approximately 7 years ]
    Defined as the absence of any immunosuppressive treatment, including sirolimus, with resolution of all reversible manifestations of chronic GVHD and no additional systemic therapy.

  • Treatment failure [ Time Frame: Approximately 7 years ]
    Defined as the initiation of additional systemic therapy, development of bronchiolitis obliterans, or death from causes other than recurrent malignancy during primary treatment for chronic GVHD, whichever occurs first.

  • Additional systemic therapy [ Time Frame: Approximately 7 years ]
    Includes any intervention intended to control chronic GVHD through an immunosuppressive effect from oral or parenteral administration of any systemic medication not originally given under auspices of this protocol.

  • Recurrent malignancy [ Time Frame: Approximately 7 years ]
    Defined as clinical or histopathologic evidence demonstrating the presence of any malignancy considered as the indication for transplant. Recurrent malignancy will also be defined as any post-transplant intervention not routinely used to prevent the development of overt recurrence, prompted by laboratory evidence of persisting malignant cells but without clinical or histopathologic evidence of recurrence.

Secondary Outcome Measures:
  • Proportion of patients who discontinue administration of sirolimus because of toxicity [ Time Frame: Every 3 months ]
  • Incidence of infections categorized by organism [ Time Frame: Every 3 months ]
  • Incidence of secondary malignancies categorized by type (lymphoma, lymphoproliferative disorders, skin cancers other than melanoma, other types of tumors) [ Time Frame: Every 3 months ]
  • Duration of treatment with prednisone [ Time Frame: Approximately 7 years ]
  • Proportion of patients with treatment success [ Time Frame: Approximately 7 years ]
  • Survival without recurrent malignancy [ Time Frame: Approximately 7 years ]
  • Overall survival [ Time Frame: Approximately 7 years ]
  • Cumulative incidence of secondary systemic treatment for chronic GVHD before recurrent malignancy [ Time Frame: Approximately 7 years ]
  • Cumulative incidence of death without recurrent malignancy [ Time Frame: Approximately 7 years ]
  • Cumulative incidence of recurrent malignancy [ Time Frame: Approximately 7 years ]

Enrollment: 44
Study Start Date: April 2002
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (GVHD prophylaxis)
Patients receive sirolimus PO QD. Patients continue to receive prednisone and cyclosporine or tacrolimus at the discretion of the managing physician.
Drug: sirolimus
Given PO
Other Names:
  • AY 22989
  • Rapamune
  • rapamycin
  • SLM
Other: questionnaire administration
Ancillary studies
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

Detailed Description:


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.


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.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT00079183

United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
National Cancer Institute (NCI)
Principal Investigator: Paul Carpenter Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

Responsible Party: Carpenter, Paul, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Identifier: NCT00079183     History of Changes
Other Study ID Numbers: 1706.00
NCI-2011-01817 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Study First Received: March 8, 2004
Last Updated: March 13, 2012

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs processed this record on March 27, 2017