Ignite Creation Date:
2024-05-05 @ 7:58 PM
Last Modification Date:
2024-10-26 @ 9:56 AM
Study NCT ID:
NCT00774358
Status:
COMPLETED
Last Update Posted:
2017-08-16
First Post:
2008-10-16
Brief Title:
Interleukin-2 Treatment for Wiskott-Aldrich Syndrome
Sponsor:
Soma Jyonouchi
Organization:
Childrens Hospital of Philadelphia
Study Overview
Official Title:
Reinstituting Natural Killer Cell Cytotoxicity and Cytoskeletal Dynamics in Wiskott-Aldrich Syndrome With IL-2 Therapy
Status:
COMPLETED
Status Verified Date:
2016-09
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:
WAS
Brief Summary:
Funding Source--FDA OOPD
Orphan Product Grant Number--1R01FD004091-01A1
Context Wiskott-Aldrich syndrome WAS is a fatal devastating disease with ill-defined treatment modalities which affects young boys Classic WAS is characterized by a clinical triad of thrombocytopenia eczema and severe recurrent infections Despite diagnostic and therapeutic advances most WAS patients die at less than 12 years of age due to infections hemorrhage malignancy or complications from treatments WAS patients suffer from herpesvirus infections as a result of poor Natural Killer NK cell function cytotoxicity In the laboratory the investigators have seen correction of WAS Natural Killer Cell NK function after treatment with Interleukin-2 IL-2
Objectives Initiate a prospective clinical trial by treating WAS subjects with IL-2 and using safety as the primary endpoint Restoration of NK cell cytotoxicity and effects on cytoskeletal dynamics are secondary endpoints The investigators will also observe patient clinical status eczema infections use of treatment dose antibiotics food allergies etc
Study DesignSettingParticipants This is a prospective clinical trial treating 9 WAS subjects in the Clinical Translational Research Center CTRC with IL-2
Intervention The investigators propose to subcutaneously administer 05 Million Units MUm2 of IL-2 daily to WAS subjects for 5 days Research treatment will be repeated 2 and 4 months later Inter-patient dose escalation will be employed to 1 MUm2 andor 2 MUm2 based on safety as the primary endpoint
Study Measures The investigators will observe safety and tolerability measures and perform assays on subject blood samples prior to and after research treatment to observe improvement in NK cell function
Orphan Product Grant Number--1R01FD004091-01A1
Context Wiskott-Aldrich syndrome WAS is a fatal devastating disease with ill-defined treatment modalities which affects young boys Classic WAS is characterized by a clinical triad of thrombocytopenia eczema and severe recurrent infections Despite diagnostic and therapeutic advances most WAS patients die at less than 12 years of age due to infections hemorrhage malignancy or complications from treatments WAS patients suffer from herpesvirus infections as a result of poor Natural Killer NK cell function cytotoxicity In the laboratory the investigators have seen correction of WAS Natural Killer Cell NK function after treatment with Interleukin-2 IL-2
Objectives Initiate a prospective clinical trial by treating WAS subjects with IL-2 and using safety as the primary endpoint Restoration of NK cell cytotoxicity and effects on cytoskeletal dynamics are secondary endpoints The investigators will also observe patient clinical status eczema infections use of treatment dose antibiotics food allergies etc
Study DesignSettingParticipants This is a prospective clinical trial treating 9 WAS subjects in the Clinical Translational Research Center CTRC with IL-2
Intervention The investigators propose to subcutaneously administer 05 Million Units MUm2 of IL-2 daily to WAS subjects for 5 days Research treatment will be repeated 2 and 4 months later Inter-patient dose escalation will be employed to 1 MUm2 andor 2 MUm2 based on safety as the primary endpoint
Study Measures The investigators will observe safety and tolerability measures and perform assays on subject blood samples prior to and after research treatment to observe improvement in NK cell function
Detailed Description:
The Wiskott-Aldrich syndrome WAS is a fatal genetic disease of the immune system that results from a mutation of the WAS protein WASp gene Immune cells that carry this mutation have a decreased ability to reorganize filamentous actin F-actin after activation As a result there are a number of defective immunologic functions some of which result in deficient host defense The investigators have identified a pervasive deficit in natural killer NK cell cytotoxicity in WAS patients WAS patients suffer from conditions that are hallmarks of NK cell deficiencies These include severe herpesvirus infections and B cell malignancies Our lab and others have also found that exposure of WAS subject NK cells to IL-2 in vitro restores NK cell function and allows for normal F-actin reorganization Thus the investigators propose a proof of principal clinical trial to treat WAS subjects with IL-2 to determine safety and efficacy of IL-2 in this population and if NK cell function is restored ex vivo If IL-2 can circumvent a defective WASp to restore NK cell function the investigators will propose a larger NIH funded efficacy trial of IL-2 in WAS The investigators will also use the in vivo treatment of WAS subjects to forward our mechanistic studies of how IL-2 may facilitate F-actin reorganization in the absence of WASp function
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 1R01FD004091-01A1 | FDA | None | httpsreporternihgovquickSearch1R01FD004091-01A1 |