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

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.

Study Overview

• Status: Completed
• Conditions: Severe Aplastic Anemia; Moderate Aplastic Anemia; Very Severe Aplastic Anemia
• Intervention / Treatment: Drug: Eltrombopag

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eltrombopag; Single arm study. Dose Escalation.	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Between weeks 1-12.
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	12 weeks
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	12 weeks
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.	Weeks 2, 6 and 12

Collaborators and Investigators

• Sponsor: University of Utah
• Collaborators: Novartis
• Investigators: Principal Investigator: George M Rodgers, M.D., University of Utah

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: September 27, 2012
• First Submitted That Met QC Criteria: October 5, 2012
• First Posted (Estimate): October 10, 2012

Study Record Updates

• Last Update Posted (Actual): October 19, 2017
• Last Update Submitted That Met QC Criteria: September 12, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: bleeding; severe aplastic anemia; very severe aplastic anemia; moderate aplastic anemia
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Bone Marrow Failure Disorders; Anemia; Anemia, Aplastic
• Other Study ID Numbers: HCI54443; ELT115895 (Other Identifier: Novartis)