Interleukin-2 Treatment for Wiskott-Aldrich Syndrome

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Brief Title

Interleukin-2 Treatment for Wiskott-Aldrich Syndrome

Official Title

Reinstituting Natural Killer Cell Cytotoxicity and Cytoskeletal Dynamics in Wiskott-Aldrich Syndrome With IL-2 Therapy

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 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.

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 Phase

Phase 1

Study Type


Primary Outcome

Safety and Tolerability

Secondary Outcome

 Evaluate effects on cytoskeletal dynamics


Wiskott-Aldrich Syndrome (WAS)



Study Arms / Comparison Groups

Description:  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.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

October 2008

Completion Date

September 2016

Primary Completion Date

September 2016

Eligibility Criteria

        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




24 Months - N/A

Accepts Healthy Volunteers



Soma Jyonouchi, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

Soma Jyonouchi


 Baylor College of Medicine

Study Sponsor

Soma Jyonouchi, MD, Principal Investigator, Children's Hospital of Philadelphia

Verification Date

September 2016