Interleukin-2 Treatment for Wiskott-Aldrich Syndrome

NCT00774358 | Completed Phase 1 DMC

• 2 other identifiers: 2007-6-53541R01FD004091-01A1
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 3

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.

Conditions

Wiskott-Aldrich Syndrome (WAS); X-linked Thrombocytopenia

Keywords

Primary Immunodeficiency

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability

  1 year

Secondary Outcomes (6)

• Evaluate effects on cytoskeletal dynamics

  1 year

• Requirement for treatment dose antibiotics

  1 year

• Number and severity of infections

  1 year

• Eczema

  1 year

• Food allergies

  1 year

Study Arms (1)

Interleukin-2

EXPERIMENTAL

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

Interventions

Interleukin-2 DRUG

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.

Also known as: IL-2, Aldesleukin, Proleukin

Interleukin-2

Eligibility Criteria

• Age: 24 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: Subjects age greater than 24 months
• Weight: Subjects greater than 12.5 kilograms
• Disease status: WAS classified as Grade 1-4

You may not qualify if:

• 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

Sponsors & Collaborators

• Soma Jyonouchi: lead
• Baylor College of Medicine: collaborator

Study Sites (3)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

The Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (9)

• Azuma H, Sakata H, Saijyou M, Okuno A. Effect of interleukin 2 on intractable herpes virus infection and chronic eczematoid dermatitis in a patient with Wiskott-Aldrich syndrome. Eur J Pediatr. 1993 Dec;152(12):998-1000. doi: 10.1007/BF01957224.

  PMID: 8131820 BACKGROUND

• Pahwa R, Chatila T, Pahwa S, Paradise C, Day NK, Geha R, Schwartz SA, Slade H, Oyaizu N, Good RA. Recombinant interleukin 2 therapy in severe combined immunodeficiency disease. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5069-73. doi: 10.1073/pnas.86.13.5069.

  PMID: 2787027 BACKGROUND

• Piscitelli SC, Wells MJ, Metcalf JA, Baseler M, Stevens R, Davey RT Jr. Pharmacokinetics and pharmacodynamics of subcutaneous interleukin-2 in HIV-infected patients. Pharmacotherapy. 1996 Sep-Oct;16(5):754-9.

  PMID: 8888071 BACKGROUND

• Witzke O, Winterhagen T, Reinhardt W, Heemann U, Grosse-Wilde H, Kreuzfelder E, Roggendorf M, Philipp T. Comparison between subcutaneous and intravenous interleukin-2 treatment in HIV disease. J Intern Med. 1998 Sep;244(3):235-40. doi: 10.1046/j.1365-2796.1998.00365.x.

  PMID: 9747746 BACKGROUND

• Toren A, Nagler A, Rozenfeld-Granot G, Levanon M, Davidson J, Bielorai B, Kaplinsky C, Meitar D, Mandel M, Ackerstein A, Ballin A, Attias D, Biniaminov M, Rosenthal E, Brok-Simoni F, Rechavi G, Kaufmann Y. Amplification of immunological functions by subcutaneous injection of intermediate-high dose interleukin-2 for 2 years after autologous stem cell transplantation in children with stage IV neuroblastoma. Transplantation. 2000 Oct 15;70(7):1100-4. doi: 10.1097/00007890-200010150-00019.

  PMID: 11045650 BACKGROUND

• Sundin DJ, Wolin MJ. Toxicity management in patients receiving low-dose aldesleukin therapy. Ann Pharmacother. 1998 Dec;32(12):1344-52. doi: 10.1345/aph.18019.

  PMID: 9876817 BACKGROUND

• Starr SE, McFarland EJ, Muresan P, Fenton T, Pitt J, Douglas SD, Deveikis A, Levin MJ, Rathore MH; PACTG 299 Study Team. Phase I/II trial of intravenous recombinant interleukin-2 in HIV-infected children. AIDS. 2003 Oct 17;17(15):2181-9. doi: 10.1097/00002030-200310170-00006.

  PMID: 14523275 BACKGROUND

• Gismondi A, Cifaldi L, Mazza C, Giliani S, Parolini S, Morrone S, Jacobelli J, Bandiera E, Notarangelo L, Santoni A. Impaired natural and CD16-mediated NK cell cytotoxicity in patients with WAS and XLT: ability of IL-2 to correct NK cell functional defect. Blood. 2004 Jul 15;104(2):436-43. doi: 10.1182/blood-2003-07-2621. Epub 2004 Mar 4.

  PMID: 15001467 BACKGROUND

• Orange JS, Brodeur SR, Jain A, Bonilla FA, Schneider LC, Kretschmer R, Nurko S, Rasmussen WL, Kohler JR, Gellis SE, Ferguson BM, Strominger JL, Zonana J, Ramesh N, Ballas ZK, Geha RS. Deficient natural killer cell cytotoxicity in patients with IKK-gamma/NEMO mutations. J Clin Invest. 2002 Jun;109(11):1501-9. doi: 10.1172/JCI14858.

  PMID: 12045264 BACKGROUND

Related Links

• Please see Study Description at www.wastherapy.com

MeSH Terms

Conditions

Wiskott-Aldrich Syndrome; Thrombocytopenia 1; Primary Immunodeficiency Diseases

Interventions

Interleukin-2; aldesleukin

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphopenia; Leukopenia; Cytopenia; Hemorrhagic Disorders; Leukocyte Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Soma Jyonouchi, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Soma Jyonouchi,MD

Study Record Dates

• First Submitted: October 16, 2008
• First Posted: October 17, 2008
• Study Start: October 1, 2008
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: August 16, 2017

Record last verified: 2016-09

Locations

US (3)