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

NCT01703169 | Completed Phase 2 Results DMC

• 2 other identifiers: HCI54443ELT115895
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Severe Aplastic Anemia; Very Severe Aplastic Anemia; Moderate Aplastic Anemia

Keywords

severe aplastic anemia; very severe aplastic anemia; moderate aplastic anemia; bleeding

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Platelet Count Twice Baseline.

  Between weeks 1-12.

• Hematology Labs

  12 weeks

• Number of Patients With AE to Measure Toxicity, Using NCI CTCAE

  12 weeks

• Characterization of the PK Profile of Eltrombopag in Patients With Moderate to Very Severe Aplastic Anemia. Evaluated With AUC, Cmax, Cmin, Tmax.

  Weeks 2, 6 and 12

Study Arms (1)

Eltrombopag

EXPERIMENTAL

Single arm study. Dose Escalation.

Drug: Eltrombopag

Interventions

Eltrombopag DRUG

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

Eltrombopag

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Utah: lead
• Novartis: collaborator

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Anemia, Aplastic; Hemorrhage

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Certain data regarding the primary outcome and adverse events were inadvertently not captured during the clinical investigation resulting in insufficient data for statistical analysis and publication.

Results Point of Contact

• Title: Kimberlee Taylor
• Organization: Huntsman Cancer Institute

Kimberlee.Taylor@hci.utah.edu

8012135673

Study Officials

• George M Rodgers, M.D.

  University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2012
• First Posted: October 10, 2012
• Study Start: November 1, 2012
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: October 19, 2017
• Results First Posted: October 19, 2017

Record last verified: 2017-09

Locations

US (1)