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

• 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: University of Utah
• Collaborator: Novartis
• Information provided by (Responsible Party): University of Utah

Tracking Information

• First Submitted Date: September 27, 2012
• First Posted Date: October 10, 2012
• Results First Submitted Date: June 16, 2017
• Results First Posted Date: October 19, 2017
• Last Update Posted Date: October 19, 2017
• Study Start Date: November 2012
• Actual Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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.

Current Secondary Outcome Measures (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 (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: 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
• 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Severe Aplastic Anemia
• Very Severe Aplastic Anemia
• Moderate Aplastic Anemia

Intervention

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

Experimental: Eltrombopag

Single arm study. Dose Escalation.

Intervention: Drug: Eltrombopag

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 27, 2016): 13
• Original Estimated Enrollment (submitted: October 5, 2012): 30
• Actual Study Completion Date: June 2016
• Actual Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01703169
• Other Study ID Numbers: HCI54443; ELT115895 ( Other Identifier: Novartis )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Utah
• Original Responsible Party: George Rodgers, University of Utah, Professor of Medicine, University of Utah
• Current Study Sponsor: University of Utah
• Original Study Sponsor: George Rodgers
• Collaborators: Novartis

Investigators

• Principal Investigator: George M Rodgers, M.D.; University of Utah

• PRS Account: University of Utah
• Verification Date: September 2017