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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
October 12, 2006
October 16, 2006
December 7, 2016
April 21, 2017
April 21, 2017
November 2005
November 2010   (Final data collection date for primary outcome measure)
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
  • Clinical activity will be monitored at 3 month intervals after the initiation of sirolimus until 2 years after the initiation of sirolimus
  • Clinical activity will be determined by ability to discontinue immunosuppression with resolution of all reversible CGVHD manifestations and no additional systemic therapy before or after the 2 year time-point
  • The primary endpoint will be evaluated at 2 years after enrollment
  • Patients will remain enrolled until death or closure of the study
Complete list of historical versions of study NCT00388362 on ClinicalTrials.gov Archive Site
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
  • Monitoring the clinical response based on completed chronic GVHD staging sheets, patient photographs, care provider documentation and physical therapy evaluations
  • Duration of treatment with prednisone
  • Treatment failure defined as inability to taper immunosuppression or need to begin additional systemic treatment for chronic GVHD
  • Monitoring toxicities including renal insufficiency, hyperlipidemia and post-transplant microangiopathic hemolytic anemia
  • Overall Survival
  • Cumulative incidence of secondary systemic treatment for chronic GVHD
  • Cumulative incidence of death without recurrent malignancy
  • Cumulative incidence of recurrent malignancy
Not Provided
Not Provided
 
Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease
A Phase II Trial of Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease
To study the effectiveness of an immunosuppressive drug sirolimus, in the treatment of chronic graft versus host disease in combination with prednisone.
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.
Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Graft vs Host Disease
  • 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
Experimental: Sirolimus Therapy
Administration of Sirolimus and Prednisone
Interventions:
  • Drug: Sirolimus
  • Drug: Prednisone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
36
August 2012
November 2010   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
13 Years and older   (Child, Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00388362
IRB-3587
96589 ( Other Identifier: Stanford University Alternate IRB Approval Number )
BMT175 ( Other Identifier: OnCore Number )
Yes
Not Provided
Plan to Share IPD: No
Laura Johnston, Stanford University
Stanford University
Not Provided
Principal Investigator: Laura Johnston Stanford University
Stanford University
March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP