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retirement of PI
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| Name | Class |
|---|---|
| Novartis Pharmaceuticals | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| WAS patients receiving Promacta | Experimental | 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 for blood drawing only | Experimental | WAS patients not receiving treatment to serve as subjects for platelet parameter studies blood drawing once only |
|
| healthy children for blood drawing only | Placebo Comparator | healthy children having blood obtained once as controls for platelet parameters study |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Promacta | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 12 Weeks |
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Inclusion Criteria:
In order to be eligible for study entry, subjects must comply with the following:
Exclusion Criteria:
Any patient is ineligible for study entry if he/she:
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| Name | Affiliation | Role |
|---|---|---|
| James B Bussel, MD | Weill Medical College of Cornell University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Weill Cornell Medical College | New York | New York | 10065 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26224646 | Derived | 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. |
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24 patients' families signed consents
11 WAS patients for treatment: 1 mother signed consent but never consented to have her very young baby start study treatment (dietary issues) + 1 withdrew
8 WAS patients' parents only were willing to have study bloods drawn
5 normal healthy children had their parents give consent for a blood draw
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| ID | Title | Description |
|---|---|---|
| FG000 | WAS Patients Treated With Promacta | 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. Promacta (eltrombopag): WAS Patients 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. Eltrombopag/promacta: Patients 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. |
| FG001 | WAS Patients for Blood Drawing Only | patients with WAS whose parents did not want them to receive treatment but were willing to let them have their blood drawn to increase the number of patients studied for platelet parameters with WAS |
| FG002 | Healthy Children | platelet parameters (primarily function) needed normal controls in children-----three were pre-op and two siblings were being tested as potential bone marrow donors |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Promacta | 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. Promacta (eltrombopag): Patients 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. Eltrombopag/promacta: Patients 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | 1 WAS subject withdrew prior to starting treatment and was not included in the analysis. Healthy volunteers were neither WAS patients nor received eltrombopag (both required for achievement of primary outcome #1). The WAS patients who were blood draw only also were 0 since they did not receive eltrombopag. | Posted | Number | participants | 12 weeks |
|
12 weeks of treatment was the focus-----subsequent information (after 12 weeks) did not demonstrate any problems
in how many patients and in how many events was there an increase in transaminases to > 2 times the upper limit of normal.
Note, one patient was never treated and thus 10, not 11, patients were evaluable for adverse events
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Promacta | 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. Promacta (eltrombopag): WAS Patients 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. Eltrombopag/promacta: Patients 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| bleeding SAE | Blood and lymphatic system disorders | Non-systematic Assessment | grade 3 or higher bleeding on WHO scale |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| increased liver tests | Hepatobiliary disorders | Systematic Assessment | transaminases > upper limit of normal but less than 2x upper limit of normal |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr james B Bussel | Weill Cornell Medicine | 917-291-5091 | jbussel@med.cornell.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 18, 2015 | Dec 21, 2018 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D014923 | Wiskott-Aldrich Syndrome |
| D013921 | Thrombocytopenia |
| D006470 | Hemorrhage |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C520809 | eltrombopag |
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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3) healthy volunteers who had their blood drawn once
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|
|
| blood drawing in patients with WAS | Diagnostic Test | blood will be drawn for platelet parameters in WAS patients not receiving treatment either because they declined or because they were ineligible |
|
| blood drawing in healthy controls | Diagnostic Test | blood will be drawn once in healthy children as controls for platelet parameters |
|
| 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 | 12 weeks |
| 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 | 12 weeks |
| BG001 | Healthy Volunteers | 5 well children having blood drawn for another reason: 3 pre-op and 2 for HLAA-typing |
| BG002 | WAS Patients for Blood Drawing Only | patients with WAS either not eligible or not interested in eltrombpopag treatment who are willing to have their blood drawn once |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Healthy Volunteers | 8 normal subjects will be studied for degree of platelet activation from one blood draw by collaborator Alan Michelson at Boston Childrens Hospital |
| OG002 | Was Patients Blood Drawing Only | WAS pts who were ineligible for or did not want eltrombopag treatment |
|
|
| Secondary | 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 | 1 subject withdrew prior to starting treatment and was not included in the analysis | Posted | Number | participants | 12 Weeks |
|
|
|
| Secondary | 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 | 1 subject withdrew prior to starting treatment and was not included in the analysis | Posted | Number | participants | 12 weeks |
|
|
|
| Secondary | 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 | 1 subject withdrew prior to starting treatment and was not included in the analysis. no treatment with eltrombopag was given to healthy volunteers and WAS patients who were blood drawing only so the effect of treatment in these 2 groups could not be assessed | Posted | Count of Participants | Participants | 12 weeks |
|
|
|
| 0 |
| 10 |
| 3 |
| 10 |
| 2 |
| 10 |
| EG001 | Healthy Volunteers | 8 normal subjects will be studied for degree of platelet activation from one blood draw by collaborator Alan Michelson at Boston Childrens Hospital | 0 | 5 | 0 | 5 | 0 | 5 |
| EG002 | WAS Patients for Blood Drawing Only | WAS patients who are either ineligible or do not want treatment but are willing to have their blood drawn once for testing | 0 | 8 | 0 | 8 | 0 | 8 |
|
| increased liver tests | Hepatobiliary disorders | Systematic Assessment | increase in transaminases to > 2X upper limit of normal |
|
|
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| D008231 | Lymphopenia |
| D007970 | Leukopenia |
| D000095542 | Cytopenia |
| D006474 | Hemorrhagic Disorders |
| D007960 | Leukocyte Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D040181 | Genetic Diseases, X-Linked |
| D000081207 | Primary Immunodeficiency Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D001791 | Blood Platelet Disorders |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|