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

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ClinicalTrials.gov Identifier: NCT01703169
Recruitment Status : Completed
First Posted : October 10, 2012
Results First Posted : October 19, 2017
Last Update Posted : October 19, 2017
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
University of Utah

Tracking Information
First Submitted Date  ICMJE September 27, 2012
First Posted Date  ICMJE October 10, 2012
Results First Submitted Date  ICMJE June 16, 2017
Results First Posted Date  ICMJE October 19, 2017
Last Update Posted Date October 19, 2017
Study Start Date  ICMJE November 2012
Actual Primary Completion Date June 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 12, 2017)
Proportion of Participants With Platelet Response [ Time Frame: up to 12 weeks ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 5, 2012)
Platelet Count Response [ Time Frame: up to 12 weeks ]
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 12, 2017)
  • Platelet Count Twice Baseline. [ Time Frame: Between weeks 1-12. ]
    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 [ Time Frame: 12 weeks ]
    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 [ Time Frame: 12 weeks ]
    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. [ Time Frame: Weeks 2, 6 and 12 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 5, 2012)
  • Platelet count twice baseline. [ Time Frame: Between weeks 1-12. ]
    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 [ Time Frame: 12 weeks ]
    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 [ Time Frame: 12 weeks ]
    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. [ Time Frame: Weeks 2, 6 and 12 ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Eltrombopag In Patients With Severe and Very Severe Aplastic Anemia
Official Title  ICMJE Efficacy and Safety of Eltrombopag In Patients With Severe and Very Severe Aplastic Anemia
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Severe Aplastic Anemia
  • Very Severe Aplastic Anemia
  • Moderate Aplastic Anemia
Intervention  ICMJE Drug: Eltrombopag
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
Study Arms  ICMJE Experimental: Eltrombopag
Single arm study. Dose Escalation.
Intervention: Drug: Eltrombopag
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 27, 2016)
13
Original Estimated Enrollment  ICMJE
 (submitted: October 5, 2012)
30
Actual Study Completion Date  ICMJE June 2016
Actual Primary Completion Date June 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01703169
Other Study ID Numbers  ICMJE HCI54443
ELT115895 ( Other Identifier: Novartis )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Utah
Study Sponsor  ICMJE University of Utah
Collaborators  ICMJE Novartis
Investigators  ICMJE
Principal Investigator: George M Rodgers, M.D. University of Utah
PRS Account University of Utah
Verification Date September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP