Efficacy and Safety of eltrombopag in patients with moderate, severe and very severe aplastic anemia

Overview

Status: Recruiting
Keywords: aplastic anemia , severe aplastic anemia
IRB Number: 00054443
Specialty: Hematology/BMT
Sub Specialties:

Brief Summary

Our hypothesis is that eltrombopag given to patients with moderate to very severe aplastic anemia will result in an increase in platelet counts. We 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. We 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 we hypothesize that plasma eltrombopag levels in peripheral blood will correlate with improved platelet counts.   

Objectives:

 

Primary Objectives:

  • To evaluate the efficacy of eltrombopag in patients with moderate to very severe aplastic anemia

 

Secondary Objectives

  • To evaluate any response, in platelet counts, to eltrombopag, in patients with moderate to very severe aplastic anemia. These would include:
    • Maximal platelet counts achieved
    • Odds of responding during weeks 4-12
    • Proportion of patients who achieve platelet counts at least twice their baseline value at any point during the study
  • To evaluate any response in hemoglobin, hematocrit, total white blood cell count, and absolute neutrophil count in patients with moderate to very severe aplastic anemia to include maximal hemoglobin, hematocrit, total white blood cell count, and absolute neutrophil counts achieved during the 12 week study period
  • To evaluate number of platelet and red cell transfusions required
  • To evaluate the safety of eltrombopag in patients with moderate to very severe aplastic anemia
  • To evaluate incidence of bleeding symptoms in study patients
  • To evaluate tolerability of study medication in study patients

·         To characterize the pharmacokinetic (PK) profile of eltrombopag in patients with moderate to very severe aplastic anemia
 

 

Principal Investigator: George Rodgers
Department: Hematology
Co Investigator: Danielle Nance

Contact Information

Name:Danielle Nance
Phone: 801-585-2626
Email: danielle.nance@hsc.utah.edu

Inclusion Criteria

Able to provide written informed consent and any other authorizations required by local law (e.g., Protected Health Information [PHI])
 

 
Male or female, > 18 years of age
 

 
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
 

Have moderate, severe, or very severe aplastic anemia and thrombocytopenia (platelet count, < 30,000 per cubic millimeter) that has persisted; for more than 1 month after initiating, or any time after completing, treatment with horse or rabbit ATG and cyclosporine.



 
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
 

 
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.