Thrombocytopenia and Bleeding in Wiskott-Aldrich Syndrome (WAS) Patients

Weill Cornell Medicine (WCM)

Status and phase: Terminated; Phase 2

Conditions: Thrombocytopenia; Wiskott-Aldrich Syndrome; Bleeding

Treatments: Drug: Promacta; Diagnostic Test: blood drawing in patients with WAS; Diagnostic Test: blood drawing in healthy controls

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00909363

0801009600

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 patients

Sex: Male

Ages: 3 months to 80 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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24 participants in 3 patient groups, including a placebo group

WAS patients receiving Promacta

Experimental group

Description:

Promacta® is commercially available in 12.5 mg, 25 mg, 50 mg, and 75 mg tablets. For this study, for young children unable to swallow a tablet, eltrombopag powder for oral suspension (Eltrombopag PfOS) will be used. PfOS is only available for investigational use at 20mg. Each sachet contains eltrombopag equivalent to 20mg per gm of powder and is reconstituted to a total of 10 ml so that the concentration is 2 mg/ml.

Treatment:

Drug: Promacta

WAS patients for blood drawing only

Experimental group

Description:

WAS patients not receiving treatment to serve as subjects for platelet parameter studies blood drawing once only

Treatment:

Diagnostic Test: blood drawing in patients with WAS

healthy children for blood drawing only

Placebo Comparator group

Description:

healthy children having blood obtained once as controls for platelet parameters study

Treatment:

Diagnostic Test: blood drawing in healthy controls