Sirolimus as Treatment of Steroid-Refractory or Steroid-Dependent Chronic Graft-Versus-Host Disease
This study has been completed.
Sponsor:
Stanford University
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
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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
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 May 23, 2013