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
  Purpose

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: Endpoint Classification: Safety/Efficacy Study
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: One year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 9
Study Start Date: October 2008
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (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.

  Eligibility

Ages Eligible for Study:   24 Months and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 (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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00774358

Contacts
Contact: Brenda Gwafila, RN 267-426-9639 gwafilab@email.chop.edu
Contact: Soma Jyonouchi, MD 215-590-2549 jyonouchi@mail.med.upenn.edu

Locations
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Brenda Gwafila, RN    267-426-9639    gwafilab@email.chop.edu   
Contact: Michele Toms, RN    215-590-7727 ext 67727    Toms@email.chop.edu   
Sub-Investigator: Paul R Gallagher, PhD         
Sub-Investigator: Rushani Saltzman, MD         
Sub-Investigator: Antonella Cianferoni, MD         
Principal Investigator: Soma Jyonouchi, MD         
Hospital of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Brenda Gwafila, RN    267-426-9636 ext 69636    gwafilab@email.chop.edu   
Contact: Michelle Toms, RN    215-590-7727 ext 67727    Toms@email.chop.edu   
United States, Texas
The Texas Children's Hospital Active, not recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Soma Jyonouchi
Investigators
Principal Investigator: Soma Jyonouchi, MD Children's Hospital of Philadelphia
  More Information

Publications:

Responsible Party: Soma Jyonouchi, Soma Jyonouchi,MD, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT00774358     History of Changes
Other Study ID Numbers: 2007-6-5354, 1R01FD004091-01A1
Study First Received: October 16, 2008
Last Updated: August 21, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Thrombocytopenia
Wiskott-Aldrich Syndrome
Genetic Diseases, X-Linked
Blood Platelet Disorders
Hematologic Diseases
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hemorrhagic Disorders
Lymphopenia
Leukopenia
Leukocyte Disorders
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes
Immune System Diseases
Interleukin-2
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 21, 2014