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

Graft vs Host Disease Clinical Trial

Official title:

A Phase II Trial of Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00388362
• Other study ID #: BMT175
• Secondary ID: 965893587
• Status: Completed
• Phase: Phase 2
• First received: October 12, 2006
• Last updated: March 29, 2013
• Start date: November 2005
• Est. completion date: October 2012

Study information

• Verified date: March 2013
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

To study the effectiveness of an immunosuppressive drug, sirolimus in the treatment of chronic graft versus host disease in combination with prednisone.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Blood and Marrow Transplant (BMT)
• Graft vs Host Disease

Intervention

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.
• Prednisone
Prednisone therapy will remain at the dose the patient received at the time sirolimus was begun.

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical activity will be monitored at 3 month intervals after the initiation of sirolimus until 2 years after the initiation of sirolimus		every 3 months until 2 years after enrollment	No
Primary	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		every month x 3 then every 3 months until 2 years post enrollment	No
Secondary	Monitoring toxicities including renal insufficiency, hyperlipidemia and post-transplant microangiopathic hemolytic anemia		every month x 3 then every 3 months until 2 years after enrollment	No
Secondary	Overall survival		every 3 months until 2 years after enrollment and with each clinic follow-up until death	Yes
Secondary	Cumulative incidence of secondary systemic treatment for chronic GVHD		every 3 months until 2 years after enrollment	No
Secondary	Cumulative incidence of death without recurrent malignancy		every 3 months until 2 years after enrollment and with each clinic follow-up until death	Yes
Secondary	Cumulative incidence of recurrent malignancy		every 3 months until 2 years after enrollment and with each clinic follow-up until death	Yes
Secondary	Monitoring the clinical response based on completed chronic GVHD staging sheets, patient photographs, care provider documentation and physical therapy evaluations		every 3 months until 2 years after enrollment	No
Secondary	Duration of treatment with prednisone		every 3 months until 2 years after enrollment	No
Secondary	Treatment failure defined as inability to taper immunosuppression or need to begin additional systemic treatment for chronic GVHD		every 3 months until 2 years after enrollment	No