Clinical trial NCT00909363: Thrombocytopenia and Bleeding in Wiskott-Aldrich Syndrome (WAS) Patients
Official title: Effects Of Eltrombopag On Thrombocytopenia, Platelet Function and Bleeding In Patients With Wiskott-Aldrich Syndrome/X-Linked Thrombocytopenia.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Wiskott-Aldrich Syndrome
Thrombocytopenia
Bleeding
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2009-05-28
Enrollment: 24
Sex: MALE
Minimum age (years): 3
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: 1. group of 11 WAS patients treated with eltrombopag
2. WAS patients who had their blood drawn once but did not receive eltrombopag treatment
3. healthy children as controls for testing only

3) healthy volunteers who had their blood drawn once
Primary purpose: TREATMENT

Brief summary: The purpose of this project is to describe the pathophysiology of thrombocytopenia and bleeding in patients with Wiskott-Aldrich Syndrome (WAS) and determine the response to thrombopoietic agents in vitro and in vivo.

Detailed description: Wiskott Aldrich Syndrome is an X-linked disease characterized by immunodeficiency, eczema and thrombocytopenia; a milder form of the disease known as X-Linked thrombocytopenia also exists. The thrombocytopenia in both WAS and XLT is characterized by: severe thrombocytopenia with platelet counts frequently less than 10-30,000/ul; small platelets which may be dysfunctional; and, as a result, a high rate of serious bleeding including intracranial hemorrhage.

Because eltrombopag has been shown to be remarkably efficacious in substantially increasing platelet counts in a high percentage of ITP patients, this study seeks to effectively treat patients who exhibit similar pathologies, as well as evaluate the state of platelets in patients with WAS and relate it to clinical bleeding. It also aims to demonstrate whether eltrombopag administered daily will enhance stem cell function, increase platelet production and platelet count, and reduce bleeding in patients with WAS.

Eligibility criteria: Inclusion Criteria:

In order to be eligible for study entry, subjects must comply with the following:

* Males from 3 months old to 80 years old
* Signed written informed consent obtained prior to study entry
* Clinical diagnosis of WAS or XLT
* Platelet levels less than 100 x 109/L
* Adequate renal and hepatic function (creatinine and bilirubin less than or equal to 1.5 x IULN, AST and ALT less than or equal to 2.5 x IULN)

Exclusion Criteria:

Any patient is ineligible for study entry if he/she:

* Over the age of 80
* Women (only males are eligible)
* fertile men who are not practicing or who are unwilling to practice birth control while enrolled in the study or until at least 6 months after treatment
* Aspirin, aspirin-containing compounds, salicylates, non-steroidal anti-inflammatory medications (NSAIDS), clopidogrel or ticlopidine, warfarin or other vitamin K antagonists, unfractionated or low molecular heparin within 7 days of first infusion
* Red blood cell transfusion in the past four weeks
* Elevated (\> 1.5 x ULN) prothrombin time (PT) or partial thromboplastin time (PTT)
* New York Heart Classification III or IV heart disease. Other severe cardiovascular or cardiopulmonary disease, including COPD.
* Known HIV infection, hepatitis B or C infection
* Any infection requiring antibiotic treatment within 3 days
* Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
* Prior malignancy with less than a 5-year disease-free interval, excluding nonmelanoma skin cancers and carcinoma in situ of the cervix

Primary outcomes:
measure: How Many WAS Patients Will Achieve Platelet Counts Above 50,000/ul.
timeFrame: 12 weeks
Secondary outcomes:
measure: Number of Patients With Wiskott-Aldrich Syndrome (WAS) With Grade 3 or Higher Bleeding or SAE (on WHO Scale)
timeFrame: 12 Weeks
measure: How Many Patients With WAS Had Abnormal Platelet Function Including Activation
timeFrame: 12 weeks
measure: How Many Patients With WAS Had Substantially Increased Platelet Production After Eltrombopag
timeFrame: 12 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: James B Bussel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gerrits AJ, Leven EA, Frelinger AL 3rd, Brigstocke SL, Berny-Lang MA, Mitchell WB, Revel-Vilk S, Tamary H, Carmichael SL, Barnard MR, Michelson AD, Bussel JB. Effects of eltrombopag on platelet count and platelet activation in Wiskott-Aldrich syndrome/X-linked thrombocytopenia. Blood. 2015 Sep 10;126(11):1367-78. doi: 10.1182/blood-2014-09-602573. Epub 2015 Jul 29.