Interleukin-2 Treatment for Wiskott-Aldrich Syndrome (WAS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Children's Hospital of Philadelphia
Sponsor:
Information provided by (Responsible Party):
Soma Jyonouchi, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier:
NCT00774358
First received: October 16, 2008
Last updated: August 21, 2014
Last verified: August 2014

October 16, 2008
August 21, 2014
October 2008
October 2015   (final data collection date for primary outcome measure)
Safety and Tolerability [ Time Frame: One year ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00774358 on ClinicalTrials.gov Archive Site
  • Evaluate effects on cytoskeletal dynamics [ Time Frame: One year ] [ Designated as safety issue: No ]
  • Requirement for treatment dose antibiotics [ Time Frame: One year ] [ Designated as safety issue: No ]
  • Number and severity of infections [ Time Frame: One year ] [ Designated as safety issue: No ]
  • Eczema [ Time Frame: One year ] [ Designated as safety issue: No ]
  • Food allergies [ Time Frame: One year ] [ Designated as safety issue: No ]
  • NK cell cytotoxicity [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Interleukin-2 Treatment for Wiskott-Aldrich Syndrome
Reinstituting Natural Killer Cell Cytotoxicity and Cytoskeletal Dynamics in Wiskott-Aldrich Syndrome With IL-2 Therapy

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 Design/Setting/Participants: 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 0.5 Million Units (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: 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.

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.

Interventional
Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Wiskott-Aldrich Syndrome (WAS)
  • X-linked Thrombocytopenia
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.
Other Names:
  • IL-2
  • Aldesleukin
  • Proleukin
Experimental: 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.
Intervention: Drug: Interleukin-2

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
9
October 2015
October 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age: Subjects age greater than 24 months
  • Weight: Subjects greater than 12.5 kilograms
  • Disease status: WAS classified as Grade 1-4
  • Informed Consent: Written informed consent of the subject (if an adult) or parental permission, and assent of the child subject provided justification is made for the inclusion of children in the study

Exclusion Criteria:

  • Prior or planned hematopoetic transplant
  • WAS classified as currently Grade 5 (autoimmune disease or malignancy)
  • Known previous reaction to IL-2
  • Subjects taking nephrotoxic, cytotoxic, cardiotoxic, or hepatotoxic medications (including medications for hypertension)
  • Subjects currently taking corticosteroids (not included here: topical and inhaled corticosteroids)
  • Subjects taking Interferon alpha
  • Use of any other investigational agent in the last 30 days
  • Women of childbearing potential not using contraception method(s), as well as women who are breastfeeding
  • Subjects with abnormal cardiac, hepatic and Central Nervous System (CNS) function
Both
24 Months and older
No
Contact: Brenda Gwafila, RN 267-426-9639 gwafilab@email.chop.edu
Contact: Soma Jyonouchi, MD 215-590-2549 jyonouchi@mail.med.upenn.edu
United States
 
NCT00774358
2007-6-5354, 1R01FD004091-01A1
Yes
Soma Jyonouchi, Children's Hospital of Philadelphia
Soma Jyonouchi
Not Provided
Principal Investigator: Soma Jyonouchi, MD Children's Hospital of Philadelphia
Children's Hospital of Philadelphia
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP