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

This study has been completed.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Paul Carpenter, Fred Hutchinson Cancer Research Center Identifier:
First received: March 8, 2004
Last updated: March 30, 2017
Last verified: March 2017
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
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
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 Paul Carpenter, 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: Approximately 7 years ]
  • Proportion With Infections Categorized by Organism [ Time Frame: Approximately 7 years ]
  • Secondary Malignancies [ Time Frame: Up to 7 years ]
    Proportion of participants who developed at least one secondary malignancy by 7 years

  • Duration of Treatment With Prednisone [ Time Frame: Approximately 7 years ]
  • Survival Without Recurrent Malignancy [ Time Frame: Approximately 7 years ]
    Kaplan-Meier estimate assessed at 7 years

  • Overall Survival [ Time Frame: Approximately 7 years ]
    Kaplan-Meier estimate assessed at 7 years

  • Cumulative Incidence of Death Without Recurrent Malignancy [ Time Frame: Approximately 7 years ]
    Analyzed with recurrent malignancy as a competing risk factor. Assessed at 7 years.

  • Cumulative Incidence of Recurrent Malignancy [ Time Frame: Approximately 7 years ]
    Analyzed with death as a competing risk factor. Assessed at 7 years.

Enrollment: 44
Study Start Date: April 2002
Study Completion Date: June 10, 2010
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sirolimus
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.
Drug: sirolimus
Given PO
Other Names:
  • AY 22989
  • Rapamune
  • rapamycin
  • SLM

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
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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
National Cancer Institute (NCI)
Principal Investigator: Paul Carpenter Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

Responsible Party: Paul Carpenter, Principal Investigator, Fred Hutchinson Cancer Research Center 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
Results First Received: March 30, 2017
Last Updated: March 30, 2017
Individual Participant Data  
Plan to Share IPD: No

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 May 25, 2017