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| Sponsors and Collaborators: |
Children's Hospital of Philadelphia Novartis |
|---|---|
| Information provided by: | Children's Hospital of Philadelphia |
| ClinicalTrials.gov Identifier: | NCT00774358 |
Purpose
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 NK cell function (cytotoxicity). In the laboratory, we 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. We will also observe patient clinical status (eczema, infections, use of treatment dose antibiotics, food allergies, etc).
Study Design/Setting/Participants: This is a prospective clinical trial treating 9 WAS subjects in the Clinical Translational Research Center (CTRC) with IL-2.
Intervention: We propose to subcutaneously administer 0.5 MU/m2 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 MU/m2 and/or 2 MU/m2 based on safety as the primary endpoint.
Study Measures: We 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.
| Condition | Intervention | Phase |
|---|---|---|
|
Wiskott-Aldrich Syndrome (WAS) |
Drug: Interleukin-2 |
Phase I |
| Study Type: | Interventional |
| Study Design: | Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study |
| Official Title: | Reinstituting Natural Killer Cell Cytotoxicity and Cytoskeletal Dynamics in Wiskott-Aldrich Syndrome With IL-2 Therapy |
| Estimated Enrollment: | 9 |
| Study Start Date: | October 2008 |
| Estimated Study Completion Date: | October 2009 |
| Estimated Primary Completion Date: | October 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
1: Experimental
Research Treatment with IL-2 for Wiskott Aldrich Syndrome.
|
Drug: Interleukin-2
We propose to subcutaneously administer 0.5 MU/m2 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 MU/m2 and/or 2 MU/m2 based on safety as the primary endpoint.
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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. We 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, we 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, we will propose a larger NIH funded efficacy trial of IL-2 in WAS. We 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.
Eligibility| Ages Eligible for Study: | 24 Months and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria
Exclusion Criteria
Contacts and Locations| Contact: Sumita Roy-Ghanta, MD | 267-426-7772 | sumita.roy-ghanta@uphs.upenn.edu |
| Contact: Jordan Orange, MD PhD | 267-426-5622 | orange@mail.med.upenn.edu |
| United States, Pennsylvania | |
| Children's Hospital of Philadelphia | Recruiting |
| Philadelphia, Pennsylvania, United States, 19104 | |
| Sub-Investigator: Eric Hanson, MD | |
| Sub-Investigator: Kimberly Nichols, MD | |
| Sub-Investigator: Paul R Gallagher, MS | |
| Study Chair: | Sumita Roy-Ghanta, MD | Children's Hospital of Philadelphia |
| Principal Investigator: | Jordan S Orange, MD PhD | Children's Hospital of Philadelphia |
More Information
| Responsible Party: | The Children's Hospital of Philadelphia ( Sumita Roy-Ghanta, MD, Study Chair ) |
| Study ID Numbers: | 2007-6-5354 |
| Study First Received: | October 16, 2008 |
| Last Updated: | December 8, 2008 |
| ClinicalTrials.gov Identifier: | NCT00774358 |
| Health Authority: | United States: Food and Drug Administration |
|
Primary Immunodeficiency |
|
Purpura Hematologic Diseases Blood Coagulation Disorders Blood Platelet Disorders Hemostatic Disorders Immunologic Deficiency Syndromes Purpura, Thrombocytopenic Thrombocytopathy |
Wiskott-Aldrich Syndrome Aldesleukin Thrombocytopenia Hemorrhagic Disorders Genetic Diseases, Inborn Interleukin-2 Genetic Diseases, X-Linked Wiskott Aldrich syndrome |
|
Disease Immune System Diseases Antineoplastic Agents Physiological Effects of Drugs Pharmacologic Actions Pathologic Processes Blood Coagulation Disorders, Inherited |
Analgesics, Non-Narcotic Sensory System Agents Syndrome Therapeutic Uses Analgesics Peripheral Nervous System Agents Central Nervous System Agents |
