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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Laura Johnston, Stanford University
ClinicalTrials.gov Identifier:
NCT00388362
First received: October 12, 2006
Last updated: March 29, 2013
Last verified: March 2013
  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
Blood and Marrow Transplant (BMT)
Drug: Sirolimus
Drug: Prednisone
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 Stanford University:

Primary Outcome Measures:
  • Clinical activity will be monitored at 3 month intervals after the initiation of sirolimus until 2 years after the initiation of sirolimus [ Time Frame: every 3 months until 2 years after enrollment ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: every month x 3 then every 3 months until 2 years post enrollment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Monitoring toxicities including renal insufficiency, hyperlipidemia and post-transplant microangiopathic hemolytic anemia [ Time Frame: every month x 3 then every 3 months until 2 years after enrollment ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: every 3 months until 2 years after enrollment and with each clinic follow-up until death ] [ Designated as safety issue: Yes ]
  • Cumulative incidence of secondary systemic treatment for chronic GVHD [ Time Frame: every 3 months until 2 years after enrollment ] [ Designated as safety issue: No ]
  • Cumulative incidence of death without recurrent malignancy [ Time Frame: every 3 months until 2 years after enrollment and with each clinic follow-up until death ] [ Designated as safety issue: Yes ]
  • Cumulative incidence of recurrent malignancy [ Time Frame: every 3 months until 2 years after enrollment and with each clinic follow-up until death ] [ Designated as safety issue: Yes ]
  • Monitoring the clinical response based on completed chronic GVHD staging sheets, patient photographs, care provider documentation and physical therapy evaluations [ Time Frame: every 3 months until 2 years after enrollment ] [ Designated as safety issue: No ]
  • Duration of treatment with prednisone [ Time Frame: every 3 months until 2 years after enrollment ] [ Designated as safety issue: No ]
  • Treatment failure defined as inability to taper immunosuppression or need to begin additional systemic treatment for chronic GVHD [ Time Frame: every 3 months until 2 years after enrollment ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: November 2005
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: sirolimus arm 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.
Drug: Prednisone
Prednisone therapy will remain at the dose the patient received at the time sirolimus was begun.

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

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:- Histologically-confirmed active chronic GVHD >100 days following allogeneic bone marrow/peripheral blood/umbilical cord blood transplantation that has failed prior therapy. In the event that histological confirmation poses undue risk, clinical evaluation is sufficient.

  • Women must have a negative pregnancy test before sirolimus administration and women of child-bearing potential agree to use a medically acceptable contraceptive throughout the treatment period and for 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/mm^3, unless receiving G-CSF to maintain neutrophil count >500/mm^3
  • Discontinuation of cyclosporine or FK506 at the time of initiating sirolimus with cyclosporine trough level <100 mg/dl and FK506 level < 5 mg/dl
  • Karnofsky performance score > or = 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 > or = 3.0 mg/dL, platelet count < or = 50,000/mm^3
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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

No publications provided

Responsible Party: Laura Johnston, Associate Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT00388362     History of Changes
Other Study ID Numbers: BMT175, 96589, 3587
Study First Received: October 12, 2006
Last Updated: March 29, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Stanford University:
GVHD

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

ClinicalTrials.gov processed this record on July 23, 2014