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

Primary Purpose

Wiskott-Aldrich Syndrome, Thrombocytopenia, Bleeding

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Promacta

blood drawing in patients with WAS

blood drawing in healthy controls

About this trial

This is an interventional treatment trial for Wiskott-Aldrich Syndrome

Eligibility Criteria

3 Months - 80 Years (Child, Adult, Older Adult)MaleAccepts 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

Sites / Locations

Weill Cornell Medical College

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

WAS patients receiving Promacta

WAS patients for blood drawing only

healthy children for blood drawing only

Arm 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.

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

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

Outcomes

Primary Outcome Measures

How Many WAS Patients Will Achieve Platelet Counts Above 50,000/ul.

number of WAS patients achieving this increase to > 50,000/uL without rescue medication in the previous 3 weeks during eltrombopag treatment

Secondary Outcome Measures

Number of Patients With Wiskott-Aldrich Syndrome (WAS) With Grade 3 or Higher Bleeding or SAE (on WHO Scale)

number of patients with bleeding SAEs while on treatment and/or number of patients with grade 3 or higher bleeding on WHO (World Health Organization) scale: the scale is from 1 to 5 with 5 = fatality and 1=very little bleeding

How Many Patients With WAS Had Abnormal Platelet Function Including Activation

in how many patients with WAS were platelets dysfunctional or activated before treatment as measured by flow cytometry to a substantial degree and the same after treatment with eltrombopag

How Many Patients With WAS Had Substantially Increased Platelet Production After Eltrombopag

in how many patients with WAS did eltrombopag increase platelet production as measured by the immature platelet fraction (IPF), a variable derived from the Sysmex auto analyzer, which is considered to be a measure of newly formed platelets ie reticulated platelets

Full Information

NCT ID

NCT00909363

First Posted

May 27, 2009

Last Updated

March 15, 2019

Sponsor

Weill Medical College of Cornell University

Collaborators

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT00909363

Brief Title

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

Acronym

WAS

Official Title

Effects Of Eltrombopag On Thrombocytopenia, Platelet Function and Bleeding In Patients With Wiskott-Aldrich Syndrome/X-Linked Thrombocytopenia.

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Terminated

Why Stopped

retirement of PI

Study Start Date

June 2009 (undefined)

Primary Completion Date

May 15, 2017 (Actual)

Study Completion Date

June 30, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Weill Medical College of Cornell University

Collaborators

Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Wiskott-Aldrich Syndrome, Thrombocytopenia, Bleeding

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

group of 11 WAS patients treated with eltrombopag WAS patients who had their blood drawn once but did not receive eltrombopag treatment healthy children as controls for testing only 3) healthy volunteers who had their blood drawn once

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

WAS patients receiving Promacta

Arm Type

Experimental

Arm Description

Arm Title

WAS patients for blood drawing only

Arm Type

Experimental

Arm Description

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

Arm Title

healthy children for blood drawing only

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Promacta

Other Intervention Name(s)

eltrombopag, revolade

Intervention Description

WAS Patients receiving treatment will start on 1 mg/kg of eltrombopag daily and be seen weekly for 12 weeks. Dose adjustment will be based on the weekly monitoring of the platelet count as utilized in ongoing studies in ITP as well as on liver tests. they will also have diagnostic blood testing prior to initiating treatment

Intervention Type

Diagnostic Test

Intervention Name(s)

blood drawing in patients with WAS

Intervention Description

blood will be drawn for platelet parameters in WAS patients not receiving treatment either because they declined or because they were ineligible

Intervention Type

Diagnostic Test

Intervention Name(s)

blood drawing in healthy controls

Intervention Description

blood will be drawn once in healthy children as controls for platelet parameters

Primary Outcome Measure Information:

Title

How Many WAS Patients Will Achieve Platelet Counts Above 50,000/ul.

Description

number of WAS patients achieving this increase to > 50,000/uL without rescue medication in the previous 3 weeks during eltrombopag treatment

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

Number of Patients With Wiskott-Aldrich Syndrome (WAS) With Grade 3 or Higher Bleeding or SAE (on WHO Scale)

Description

Time Frame

12 Weeks

Title

How Many Patients With WAS Had Abnormal Platelet Function Including Activation

Description

in how many patients with WAS were platelets dysfunctional or activated before treatment as measured by flow cytometry to a substantial degree and the same after treatment with eltrombopag

Time Frame

12 weeks

Title

How Many Patients With WAS Had Substantially Increased Platelet Production After Eltrombopag

Description

Time Frame

12 weeks

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

3 Months

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

James B Bussel, MD

Organizational Affiliation

Weill Medical College of Cornell University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Weill Cornell Medical College

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

26224646

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.

Results Reference

derived

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

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