AzTrials
AzTrials

Wiskott-Aldrich Syndrome (WAS)Phase 1WASNCT00774358

Interleukin-2 Treatment for Wiskott-Aldrich Syndrome

A Phase 1 study testing Interleukin-2 in people with Wiskott-Aldrich Syndrome (WAS) and X-linked Thrombocytopenia, run by Soma Jyonouchi at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 24 months and older
What is being tested?
Interleukin-2
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
3 sitesUnited States
Study dates
Oct 2008to Sep 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 24 months and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 10Show fewer
  • 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

Trial locations and contacts

3 sites in 1 country.

United States3 sites
  • The Texas Children's Hospital

    Houston, Texas, 77030

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

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

Funding Source--FDA OOPD.

Orphan Product Grant Number--1R01FD004091-01A1

Read more

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.

Read the 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.

Being tested
Interleukin-2
Keywords
Primary Immunodeficiency
Medical subject headings
Wiskott-Aldrich Syndrome, Thrombocytopenia 1, Primary Immunodeficiency Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Interleukin-2Drug

    Also called IL-2, Aldesleukin, Proleukin

    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.

Study groups in NCT00774358
Study groupRoleWhat they receive
Interleukin-2ExperimentalWe 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.
Receives: Drug: Interleukin-2

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and Tolerability

    Measured: 1 year

Secondary outcomes (6)
  1. Evaluate effects on cytoskeletal dynamics

    Measured: 1 year

  2. Requirement for treatment dose antibiotics

    Measured: 1 year

  3. Number and severity of infections

    Measured: 1 year

  4. Eczema

    Measured: 1 year

  5. Food allergies

    Measured: 1 year

  6. NK cell cytotoxicity

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Oct 2008 (estimated)
  2. Study startOct 2008
  3. Primary completionSep 2016
  4. Study completionSep 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00774358
Sponsor's protocol ID
2007-6-5354
Other IDs
1R01FD004091-01A1
Acronym
WAS
Status last verified
Sep 2016
First submitted
16 Oct 2008
Last updated
16 Aug 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 8131820
  • 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.

    PubMed 2787027
  • 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.

    PubMed 8888071
  • 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.

    PubMed 9747746
  • 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.

    PubMed 11045650
  • 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.

    PubMed 9876817
  • 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.

    PubMed 14523275
  • 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.

    PubMed 15001467
  • 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.

    PubMed 12045264

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Interleukin-2 in people with Wiskott-Aldrich Syndrome (WAS) and X-linked Thrombocytopenia, run by Soma Jyonouchi at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Tolerability (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00774358, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2017.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in