Interleukin-2 Treatment for Wiskott-Aldrich Syndrome

Learn more about:
Related Clinical Trial
Romiplostim Treatment for Thrombocytopenia in Patients With Wiskott-Aldrich Syndrome. Efficacy and Safety of Romiplostim Versus Eltrombopag in the Treatment of Thrombocytopenia in Patients With Wiskott-Aldrich Syndrome Bone Marrow Transplant With Abatacept for Non-Malignant Diseases Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies Alpha/Beta T and CD19+ Depleted Peripheral Stem Cells for Patients With Primary Immunodeficiencies Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation Long-term Study of Romiplostim in Thrombocytopenic Pediatric Patients With Immune Thrombocytopenia (ITP) Participation in a Research Registry for Immune Disorders Haploidentical Hematopoietic Stem Cell Transplantation Patients With Wiskott-Aldrich Syndrome Gene Therapy for Wiskott-Aldrich Syndrome (WAS) Study of Reduced Toxicity Myeloablative Conditioning Regimen for Wiskott-Aldrich Syndrome (WAS) Patients Treated for Wiskott-Aldrich Syndrome (WAS) Since 1990 A Clinical Study to Evaluate the Use of a Cryopreserved Formulation of OTL-103 in Subjects With Wiskott-Aldrich Syndrome Post-transplant Cyclophosphamide in Wiskott-Aldrich Syndrome Long Term Safety Follow up of Haematopoietic Stem Cell Gene Therapy for the Wiskott Aldrich Syndrome Thrombocytopenia and Bleeding in Wiskott-Aldrich Syndrome (WAS) Patients Pilot and Feasibility Study of Hematopoietic Stem Cell Gene Transfer for the Wiskott-Aldrich Syndrome Interleukin-2 Treatment for Wiskott-Aldrich Syndrome Gene Therapy for WAS Targeted Literature Review and Subject Interviews in Wiskott-Aldrich Syndrome (WAS) Molecular and Clinical Studies of Primary Immunodeficiency Diseases A Trial of Plerixafor/G-CSF as Additional Agents for Conditioning Before TCR Alpha/Beta Depleted HSCT in WAS Patients

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

Interventional


Primary Outcome

Safety and Tolerability

Secondary Outcome

 Evaluate effects on cytoskeletal dynamics

Condition

Wiskott-Aldrich Syndrome (WAS)

Intervention

Interleukin-2

Study Arms / Comparison Groups

 Interleukin-2
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.

Publications

* 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

Drug

Estimated Enrollment

9

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
      

Gender

All

Ages

24 Months - N/A

Accepts Healthy Volunteers

No

Contacts

Soma Jyonouchi, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00774358

Organization ID

2007-6-5354

Secondary IDs

1R01FD004091-01A1

Responsible Party

Sponsor-Investigator

Study Sponsor

Soma Jyonouchi

Collaborators

 Baylor College of Medicine

Study Sponsor

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


Verification Date

September 2016