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Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00388362
First Posted: October 16, 2006
Last Update Posted: April 21, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Laura Johnston, Stanford University
  Purpose
To study the effectiveness of an immunosuppressive drug sirolimus, in the treatment of chronic graft versus host disease in combination with prednisone.

Condition Intervention Phase
Graft vs Host Disease Drug: Sirolimus Drug: Prednisone Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease

Resource links provided by NLM:


Further study details as provided by Laura Johnston, Stanford University:

Primary Outcome Measures:
  • Clinical Activity [ Time Frame: 3 month intervals after the initiation of sirolimus until 2 years after the initiation of sirolimus ]
    Determined by discontinuation of immunosuppression with resolution of all reversible CGVHD manifestations. Evaluated at 2 years after enrollment


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 3 month intervals after the initiation of sirolimus until 2 years after the initiation of sirolimus ]
    Administration of Sirolimus and Prednisone


Enrollment: 36
Study Start Date: November 2005
Study Completion Date: August 2012
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sirolimus Therapy
Administration of Sirolimus and Prednisone
Drug: Sirolimus
Patients will receive sirolimus at 2 mg/day orally with monitoring of trough drug levels weekly for 2 weeks to achieve trough drug levels 7-12 ng/ml. Along with prednisone therapy.
Other Name: Rapamune
Drug: Prednisone
Prednisone therapy will remain at the dose the patient received at the time sirolimus was begun. Withdrawal of prednisone will began after first evidence of improvement of chronic GVHD.
Other Name: Deltasone

Detailed Description:
The purpose of this trial is to study the effectiveness of an immunosuppressive drug, sirolimus, in the treatment of chronic graft versus host disease in combination with prednisone. Graft versus host disease (GVHD) is a common complication in patients who have received blood or marrow transplantation from a related or unrelated donor. Chronic GVHD occurs approximately 100 days after transplantation and is the result of the donor immune system recognizing the patient's tissues as foreign and creating harmful effects on the patient's organs. We hope the use of sirolimus will decrease the significant disabling effects and deaths caused by chronic GVHD.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   13 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 13 years
  • Weight ≥ 40 kg.
  • Biopsy or clinical presentation diagnostic of chronic GVHD >100 days following allogeneic bone marrow/peripheral blood/umbilical cord blood transplantation that has failed prior corticosteroid therapy or corticosteroid taper. In the event that histological confirmation poses undue risk, clinical evaluation is sufficient.
  • Women of child-bearing potential must have a negative pregnancy test before sirolimus administration and agree to use a medically acceptable contraceptive throughout the treatment period until 3 months after discontinuation of sirolimus.
  • Any woman becoming pregnant during the treatment period must discontinue the use of sirolimus.
  • Absolute neutrophil count (ANC) > 1000/mm³, unless receiving G-CSF to maintain neutrophil count > 500/mm³.
  • At the time of initiating sirolimus the cyclosporine trough level is recommended to be < 100 mg/dl and FK506 level is recommended to be < 5 mg/dl. FK506 or cyclosporine is to be discontinued soon after initiation of sirolimus.
  • Karnofsky performance score ≥ 50 during pre-study screening.
  • Written, signed, and dated informed consent

Exclusion Criteria:

  • Uncontrolled systemic infection
  • Unstable disease states (i.e., hepatic failure, ventilatory-dependent respiratory failure, etc.)
  • Serum creatinine ≥ 3.0 mg/dL
  • Platelet count ≤ 50,000/mm³
  • History of Post-transplant microangiopathic hemolytic anemia
  • Uncontrolled hyperlipidemia
  • Use of any investigational drug within 4 weeks of entry into the study
  • Use of methotrexate or antibody therapies within 24 hours of sirolimus administration
  • Inability to tolerate oral therapy for any reason
  • Evidence of infiltrate, cavitation, or consolidation on chest x-ray during pre-study screening
  • Known hypersensitivity to macrolide antibiotics
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00388362


Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Laura Johnston Stanford University
  More Information

Responsible Party: Laura Johnston, Associate Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT00388362     History of Changes
Other Study ID Numbers: IRB-3587
96589 ( Other Identifier: Stanford University Alternate IRB Approval Number )
BMT175 ( Other Identifier: OnCore Number )
First Submitted: October 12, 2006
First Posted: October 16, 2006
Results First Submitted: December 7, 2016
Results First Posted: April 21, 2017
Last Update Posted: April 21, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Laura Johnston, Stanford University:
GVHD

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Prednisone
Sirolimus
Everolimus
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors