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Trial record 1 of 2 for:    "X-linked thrombocytopenia"
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Interleukin-2 Treatment for Wiskott-Aldrich Syndrome (WAS)

This study has been completed.
Texas Children's Hospital
Information provided by (Responsible Party):
Soma Jyonouchi, Children's Hospital of Philadelphia Identifier:
First received: October 16, 2008
Last updated: September 2, 2016
Last verified: September 2016

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.

Condition Intervention Phase
Wiskott-Aldrich Syndrome (WAS)
X-linked Thrombocytopenia
Drug: Interleukin-2
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Reinstituting Natural Killer Cell Cytotoxicity and Cytoskeletal Dynamics in Wiskott-Aldrich Syndrome With IL-2 Therapy

Resource links provided by NLM:

Further study details as provided by Children's Hospital of Philadelphia:

Primary Outcome Measures:
  • Safety and Tolerability [ Time Frame: 1 year ]

Secondary Outcome Measures:
  • Evaluate effects on cytoskeletal dynamics [ Time Frame: 1 year ]
  • Requirement for treatment dose antibiotics [ Time Frame: 1 year ]
  • Number and severity of infections [ Time Frame: 1 year ]
  • Eczema [ Time Frame: 1 year ]
  • Food allergies [ Time Frame: 1 year ]
  • NK cell cytotoxicity [ Time Frame: 1 year ]

Enrollment: 9
Study Start Date: October 2008
Study Completion Date: September 2016
Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

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.

Ages Eligible for Study:   24 Months and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 (Malignancy or autoimmune disease including the following: Crohn's disease, scleroderma, thyroiditis, inflammatory arthritis, diabetes mellitus, oculo-bulbar myasthenia gravis, crescentic IgA glomerulonephritis, cholecystitis, cerebral vasculitis, Stevens-Johnson syndrome and bullous pemphigoid . Not included here are: Hepatitis C virus induced vasculitis, alopecia areata and systemic lupus erythematosus.)
  • Known previous reaction to IL-2
  • Subjects taking immunosuppressive medications that might alter study results
  • Subjects taking nephrotoxic, cytotoxic, cardiotoxic, or hepatotoxic medications (including medications for hypertension)
  • Subjects currently taking systemic 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 CNS function
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Please refer to this study by its identifier: NCT00774358

United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
The Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Soma Jyonouchi
Texas Children's Hospital
Principal Investigator: Soma Jyonouchi, MD Children's Hospital of Philadelphia
  More Information


Responsible Party: Soma Jyonouchi, Soma Jyonouchi,MD, Children's Hospital of Philadelphia Identifier: NCT00774358     History of Changes
Other Study ID Numbers: 2007-6-5354
1R01FD004091-01A1 ( US NIH Grant/Contract Award Number )
Study First Received: October 16, 2008
Last Updated: September 2, 2016

Keywords provided by Children's Hospital of Philadelphia:
Primary Immunodeficiency

Additional relevant MeSH terms:
Wiskott-Aldrich Syndrome
Genetic Diseases, X-Linked
Pathologic Processes
Blood Platelet Disorders
Hematologic Diseases
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hemorrhagic Disorders
Leukocyte Disorders
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes
Immune System Diseases
Antineoplastic Agents
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs processed this record on May 25, 2017