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Efficacy and Safety of Eltrombopag In Patients With Severe and Very Severe Aplastic Anemia

Primary Purpose

Severe Aplastic Anemia, Very Severe Aplastic Anemia, Moderate Aplastic Anemia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Eltrombopag
Sponsored by
University of Utah
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Severe Aplastic Anemia focused on measuring severe aplastic anemia, very severe aplastic anemia, moderate aplastic anemia, bleeding

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Able to provide written informed consent and any other authorizations required by local law (e.g., Protected Health Information [PHI])
  • Have severe or very severe aplastic anemia, or moderate aplastic anemia with platelet counts that have dropped below 20,000/μl
  • Have moderate, severe, or very severe aplastic anemia with moderate bleeding during or after a surgical procedure, (including bone marrow biopsy, lumbar puncture, thoracentesis, paracentesis, port placement, dermal biopsy) or minimal mucocutaneous bleeding otherwise noted
  • Subjects with current or previous exposure to approved medications for the treatment of aplastic anemia will not be excluded; these include but may not be limited to, anti-thymocyte globulin (ATG), cyclosporine, corticosteroids, and G-CSF.

Exclusion Criteria:

  • Have diagnosis of Fanconi anemia
  • Have infection not adequately responding to appropriate therapy
  • Have Paroxysmal Nocturnal Hemoglobinuria (PNH) clone size in neutrophils of greater than or equal to 50%
  • Have known HIV positivity
  • Have creatinine and/or blood urea nitrogen (BUN) ≥2 times the upper limit of normal
  • Have serum bilirubin ≥ 1.5 times the upper limit of normal, or ≥4.0 times the upper limit of normal if the patient has been treated with ATG within three weeks of screening.
  • Have AST and/or ALT ≥ 3 times the upper limit of normal
  • Have hypersensitivity to eltrombopag or its components
  • Have chemotherapy given less than or equal to 14 days prior to initiating the study medication. This does not include immunosuppressive agents and growth factor as described above
  • Are female and are nursing or pregnant or are unwilling to take oral contraceptives or refrain from pregnancy if of childbearing potential
  • Are unable to understand the investigational nature of the study or give informed consent
  • Have a history of arterial or venous thrombosis within the last 1 year (excluding those due to indwelling lines)
  • Have an ECOG performance status of 3 or greater
  • Have had treatment with Campath within 6 months of entry into the study
  • Have pre-existing cardiovascular disease (congestive heart failure with New York Heart Association [NYHA] grade III/IV), arrhythmia known to increase the risk of thromboembolic events (e.g. atrial fibrillation), unstable angina, or QTc > 450 msec (QTc 480 msec for subjects with bundle branch block), or myocardial infarction within the preceding 6 months) at study entry
  • Have had other TPO-R agonists medication in the previous 4 weeks.

Sites / Locations

  • University of Utah

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Eltrombopag

Arm Description

Single arm study. Dose Escalation.

Outcomes

Primary Outcome Measures

Proportion of Participants With Platelet Response
Defined as a stable platelet count of 50,000/μl or more during any 4 week period within the possible 12 weeks while on study,and including maximal platelet counts achieved in patients with moderate to very severe aplastic anemia.

Secondary Outcome Measures

Platelet Count Twice Baseline.
Proportion of subjects who achieve platelet counts at least twice their baseline value at any point while on study medication, in patients with moderate to very severe aplastic anemia.
Hematology Labs
Association between eltrombopag use and response in hemoglobin, hematocrit, total white blood cell count, and absolute neutrophil count to be evaluate by maximal hemoglobin, hematocrit, total white blood cell count, and absolute neutrophil counts achieved in patients with moderate to very severe aplastic anemia
Number of Patients With AE to Measure Toxicity, Using NCI CTCAE
Evaluated weekly, up to 12 weeks. Association between eltrombopag use, dose, and tolerability in patients with moderate to very severe aplastic anemia
Characterization of the PK Profile of Eltrombopag in Patients With Moderate to Very Severe Aplastic Anemia. Evaluated With AUC, Cmax, Cmin, Tmax.
Samples will for PK analysis will collected as a trough level weeks 2, 6 and 12, prior to dose of eltrombopag. Additional PK level drawn at 2, 4 and 6 hours post-dose at the scheduled week 2 visit.

Full Information

First Posted
September 27, 2012
Last Updated
September 12, 2017
Sponsor
University of Utah
Collaborators
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT01703169
Brief Title
Efficacy and Safety of Eltrombopag In Patients With Severe and Very Severe Aplastic Anemia
Official Title
Efficacy and Safety of Eltrombopag In Patients With Severe and Very Severe Aplastic Anemia
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
November 2012 (undefined)
Primary Completion Date
June 2016 (Actual)
Study Completion Date
June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Utah
Collaborators
Novartis

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The investigators hypothesis is that eltrombopag given to patients with moderate to very severe aplastic anemia will result in an increase in platelet counts. The investigators hypothesize that in patients with moderate to very severe aplastic anemia, treatment with eltrombopag will lead to fewer platelet transfusions, red blood cell transfusions, and fewer bleeding events. The investigators hypothesize that in patients with moderate to very severe aplastic anemia, eltrombopag will have an acceptable toxicity rate <3%, at doses that result in increased platelet counts. Finally the investigators hypothesize that plasma eltrombopag levels in peripheral blood will correlate with improved platelet counts.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Aplastic Anemia, Very Severe Aplastic Anemia, Moderate Aplastic Anemia
Keywords
severe aplastic anemia, very severe aplastic anemia, moderate aplastic anemia, bleeding

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Eltrombopag
Arm Type
Experimental
Arm Description
Single arm study. Dose Escalation.
Intervention Type
Drug
Intervention Name(s)
Eltrombopag
Intervention Description
Oral eltrombopag 150mg/day by mouth starting on Day 1 with dose modification over 12 weeks to a maximum of 300mg/day determined by platelet count
Primary Outcome Measure Information:
Title
Proportion of Participants With Platelet Response
Description
Defined as a stable platelet count of 50,000/μl or more during any 4 week period within the possible 12 weeks while on study,and including maximal platelet counts achieved in patients with moderate to very severe aplastic anemia.
Time Frame
up to 12 weeks
Secondary Outcome Measure Information:
Title
Platelet Count Twice Baseline.
Description
Proportion of subjects who achieve platelet counts at least twice their baseline value at any point while on study medication, in patients with moderate to very severe aplastic anemia.
Time Frame
Between weeks 1-12.
Title
Hematology Labs
Description
Association between eltrombopag use and response in hemoglobin, hematocrit, total white blood cell count, and absolute neutrophil count to be evaluate by maximal hemoglobin, hematocrit, total white blood cell count, and absolute neutrophil counts achieved in patients with moderate to very severe aplastic anemia
Time Frame
12 weeks
Title
Number of Patients With AE to Measure Toxicity, Using NCI CTCAE
Description
Evaluated weekly, up to 12 weeks. Association between eltrombopag use, dose, and tolerability in patients with moderate to very severe aplastic anemia
Time Frame
12 weeks
Title
Characterization of the PK Profile of Eltrombopag in Patients With Moderate to Very Severe Aplastic Anemia. Evaluated With AUC, Cmax, Cmin, Tmax.
Description
Samples will for PK analysis will collected as a trough level weeks 2, 6 and 12, prior to dose of eltrombopag. Additional PK level drawn at 2, 4 and 6 hours post-dose at the scheduled week 2 visit.
Time Frame
Weeks 2, 6 and 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Able to provide written informed consent and any other authorizations required by local law (e.g., Protected Health Information [PHI]) Have severe or very severe aplastic anemia, or moderate aplastic anemia with platelet counts that have dropped below 20,000/μl Have moderate, severe, or very severe aplastic anemia with moderate bleeding during or after a surgical procedure, (including bone marrow biopsy, lumbar puncture, thoracentesis, paracentesis, port placement, dermal biopsy) or minimal mucocutaneous bleeding otherwise noted Subjects with current or previous exposure to approved medications for the treatment of aplastic anemia will not be excluded; these include but may not be limited to, anti-thymocyte globulin (ATG), cyclosporine, corticosteroids, and G-CSF. Exclusion Criteria: Have diagnosis of Fanconi anemia Have infection not adequately responding to appropriate therapy Have Paroxysmal Nocturnal Hemoglobinuria (PNH) clone size in neutrophils of greater than or equal to 50% Have known HIV positivity Have creatinine and/or blood urea nitrogen (BUN) ≥2 times the upper limit of normal Have serum bilirubin ≥ 1.5 times the upper limit of normal, or ≥4.0 times the upper limit of normal if the patient has been treated with ATG within three weeks of screening. Have AST and/or ALT ≥ 3 times the upper limit of normal Have hypersensitivity to eltrombopag or its components Have chemotherapy given less than or equal to 14 days prior to initiating the study medication. This does not include immunosuppressive agents and growth factor as described above Are female and are nursing or pregnant or are unwilling to take oral contraceptives or refrain from pregnancy if of childbearing potential Are unable to understand the investigational nature of the study or give informed consent Have a history of arterial or venous thrombosis within the last 1 year (excluding those due to indwelling lines) Have an ECOG performance status of 3 or greater Have had treatment with Campath within 6 months of entry into the study Have pre-existing cardiovascular disease (congestive heart failure with New York Heart Association [NYHA] grade III/IV), arrhythmia known to increase the risk of thromboembolic events (e.g. atrial fibrillation), unstable angina, or QTc > 450 msec (QTc 480 msec for subjects with bundle branch block), or myocardial infarction within the preceding 6 months) at study entry Have had other TPO-R agonists medication in the previous 4 weeks.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
George M Rodgers, M.D.
Organizational Affiliation
University of Utah
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States

12. IPD Sharing Statement

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Efficacy and Safety of Eltrombopag In Patients With Severe and Very Severe Aplastic Anemia

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