Ignite Creation Date:
2024-05-05 @ 5:08 PM
Last Modification Date:
2024-10-26 @ 9:28 AM
Study NCT ID:
NCT00392951
Status:
COMPLETED
Last Update Posted:
2019-11-19
First Post:
2006-10-24
Brief Title:
Sirolimus for Autoimmune Disease of Blood Cells
Sponsor:
Childrens Hospital of Philadelphia
Organization:
Childrens Hospital of Philadelphia
Study Overview
Official Title:
Sirolimus for Patients With Chronic andor Refractory Autoimmune Cytopenias A Pilot Series
Status:
COMPLETED
Status Verified Date:
2019-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Treatment for patients with autoimmune destruction of blood cells is poor The part of the body that fights infections is called the immune system and white blood cells WBCs are part of the immune system Normally a persons body creates WBCs to fight infections and eliminates WBCs which have stopped helping the body function Patients with autoimmune destruction of blood cells have difficulty eliminating old WBCs The abnormal WBCs build up and can damage other healthy cells which can lead to anemia fatigue jaundice internal bleeding infection and cancer Few effective medications exist for treatment for patients with autoimmune cytopenias and those commonly used are fraught with side effects Nevertheless as scientific understanding of autoimmune diseases has improved more directed and less toxic therapies are becoming available A number of groups have been studying the efficacy of a medication called sirolimus in patients with autoimmune diseases This medicine has been FDA-approved for over 20 years Sirolimus is a medicine used in children with other diseases Sirolimus works in part by eliminating old and abnormal WBCs Our group and others have shown that sirolimus is effective in mice with autoimmunity and in children with a rare condition called Autoimmune Lymphoproliferative Syndrome ALPS We believe sirolimus will help children with autoimmune cytopenias We believe it will improve their symptoms and make them less sick We propose to study sirolimus in children with chronic andor refractory autoimmune cytopenias
Detailed Description:
Patients with autoimmune destruction of hematopoietic cells frequently have severe and debilitating disease requiring aggressive and frequent medical management These patients are often treated with non-specific immunosuppressive medications with limited efficacy and untoward side-effect profiles We have been investigating the use of an immunosuppressive and anti-cancer agent sirolimus in patients with an autoimmune cytopenias syndrome Autoimmune Lymphoproliferative Syndrome ALPS ALPS is a primary immune deficiency caused by mutations in the Fas apoptotic pathway leading to abnormal lymphocyte survival Clinical manifestations in patients with ALPS typically include autoimmune cytopenias lymphadenopathy hepatosplenomegaly and a propensity to develop secondary malignancies Thus far we have found excellent results albeit the total number of patients treated is small
Sirolimus is a signal transduction inhibitor with a tolerable side effect profile Sirolimus has two properties making it an attractive agent to treat patients with autoimmune cytopenias syndromes including ALPS First sirolimus induces apoptosis in normal and abnormal white blood cells the cell type dysregulated in patients with autoimmune disease In addition sirolimus increases a T cell subset called Regulatory T cells Tregs Tregs are a cell population designed to suppress the immune system and control autoimmunity These combined properties make sirolimus unique as compared with other immunosuppressive agents Ample preclinical and clinical data exists demonstrating sirolimus in effective in patients with autoimmunity Accordingly we hypothesize sirolimus is a safe and efficacious medication for patients with autoimmune destruction of blood cells
We plan to confirm our hypotheses by performing a pilot series in children with autoimmune cytopenias who are either refractory to standard therapy or have significant toxicity from standard treatments Our primary aim is to define the toxicities of administration of oral sirolimus in children with autoimmune cytopenias Our secondary aims are to evaluate the efficacy of sirolimus in children with autoimmune cytopenias to determine the trough levels of sirolimus when used in these patients and to evaluate the effects of sirolimus on intracellular targets of mammalian target of rapamycin mTOR We intend to enroll 50 children with autoimmune cytopenias and treat for a 6 month period however if we find sirolimus is effective we anticipate these children will continue to take sirolimus for a longer period of time We anticipate the results of this work will establish sirolimus is an effective and well tolerated medication and will lead directly to a larger national phase II clinical trial
Sirolimus is a signal transduction inhibitor with a tolerable side effect profile Sirolimus has two properties making it an attractive agent to treat patients with autoimmune cytopenias syndromes including ALPS First sirolimus induces apoptosis in normal and abnormal white blood cells the cell type dysregulated in patients with autoimmune disease In addition sirolimus increases a T cell subset called Regulatory T cells Tregs Tregs are a cell population designed to suppress the immune system and control autoimmunity These combined properties make sirolimus unique as compared with other immunosuppressive agents Ample preclinical and clinical data exists demonstrating sirolimus in effective in patients with autoimmunity Accordingly we hypothesize sirolimus is a safe and efficacious medication for patients with autoimmune destruction of blood cells
We plan to confirm our hypotheses by performing a pilot series in children with autoimmune cytopenias who are either refractory to standard therapy or have significant toxicity from standard treatments Our primary aim is to define the toxicities of administration of oral sirolimus in children with autoimmune cytopenias Our secondary aims are to evaluate the efficacy of sirolimus in children with autoimmune cytopenias to determine the trough levels of sirolimus when used in these patients and to evaluate the effects of sirolimus on intracellular targets of mammalian target of rapamycin mTOR We intend to enroll 50 children with autoimmune cytopenias and treat for a 6 month period however if we find sirolimus is effective we anticipate these children will continue to take sirolimus for a longer period of time We anticipate the results of this work will establish sirolimus is an effective and well tolerated medication and will lead directly to a larger national phase II clinical trial
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None