Sirolimus as Secondary Therapy in Chronic Graft-Versus-Host Disease Not Responding To Prior Treatment
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
|Official Title:||A Phase II Clinical Trial to Evaluate the Safety and Efficacy of Sirolimus for Secondary Treatment of Chronic Graft-versus-Host Disease|
- Number of Participants Experiencing Treatment Success [ Time Frame: Approximately 7 years ]Defined as the absence of any immunosuppressive treatment, including sirolimus, with resolution of all reversible manifestations of chronic GVHD and no additional systemic therapy.
- Number of Participants Experiencing Treatment Failure [ Time Frame: Approximately 7 years ]Defined as the initiation of additional systemic therapy, development of bronchiolitis obliterans, or death from causes other than recurrent malignancy during primary treatment for chronic GVHD, whichever occurs first.
- Number of Participants Needing Additional Systemic Therapy [ Time Frame: Approximately 7 years ]Includes any intervention intended to control chronic GVHD through an immunosuppressive effect from oral or parenteral administration of any systemic medication not originally given under auspices of this protocol.
- Number of Participants With Recurrent Malignancy [ Time Frame: Approximately 7 years ]Defined as clinical or histopathologic evidence demonstrating the presence of any malignancy considered as the indication for transplant. Recurrent malignancy will also be defined as any post-transplant intervention not routinely used to prevent the development of overt recurrence, prompted by laboratory evidence of persisting malignant cells but without clinical or histopathologic evidence of recurrence.
- Proportion of Patients Who Discontinue Administration of Sirolimus Because of Toxicity [ Time Frame: Approximately 7 years ]
- Proportion With Infections Categorized by Organism [ Time Frame: Approximately 7 years ]
- Secondary Malignancies [ Time Frame: Up to 7 years ]Proportion of participants who developed at least one secondary malignancy by 7 years
- Duration of Treatment With Prednisone [ Time Frame: Approximately 7 years ]
- Probability of Survival Without Recurrent Malignancy [ Time Frame: Approximately 7 years ]Kaplan-Meier estimate assessed at 7 years for probability of survival without recurrent malignancy.
- Probability of Overall Survival [ Time Frame: Approximately 7 years ]Kaplan-Meier estimate assessed at 7 years
- Probability of Cumulative Incidence of Death Without Recurrent Malignancy [ Time Frame: Approximately 7 years ]Analyzed with recurrent malignancy as a competing risk factor. Assessed at 7 years.
- Probability of Cumulative Incidence of Recurrent Malignancy [ Time Frame: Approximately 7 years ]Analyzed with death as a competing risk factor. Assessed at 7 years.
|Study Start Date:||April 2002|
|Study Completion Date:||June 10, 2010|
|Primary Completion Date:||July 2009 (Final data collection date for primary outcome measure)|
Study participants receive sirolimus added once daily to their baseline combination therapy of prednisone plus either cyclosporine or tacrolimus at the discretion of the managing physician. Treatment other than cyclosporine (or tacrolimus) and prednisone must be discontinued when administration of sirolimus is started. Topical therapy, including psoralen and UVA irradiation (PUVA), glucocorticoid creams, topical tacrolimus, oral beclomethasone, topical azathioprine and ophthalmic glucocorticoids may be given at the discretion of the managing physician in consultation with the transplant center.
I. To assess the safety of sirolimus administered at a dose which provides steady-state, whole blood trough levels of 5-10 ng/mL in patients with chronic GVHD.
II. To determine whether administration of sirolimus provides benefit for patients with chronic GVHD that has not responded adequately to previous systemic treatment.
Patients receive sirolimus orally (PO) once daily (QD). Patients continue to receive prednisone and cyclosporine or tacrolimus at the discretion of the managing physician.
After completion of study treatment, patients are followed up periodically.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00079183
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Paul Carpenter||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|