Moderate Aplastic Anemia, Severe Aplastic Anemia, Very Severe Aplastic Anemia
Conditions
Keywords
severe aplastic anemia, very severe aplastic anemia, moderate aplastic anemia, bleeding
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.
Interventions
DRUGEltrombopag
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
Sponsors
Novartis
University of Utah
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Platelet Response | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Platelet Count Twice Baseline. | 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 | 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 | 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. | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Eltrombopag Single arm study. Dose Escalation.
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 | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Eltrombopag |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 13 Count of Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 13 |
| other Total, other adverse events | 13 / 13 |
| serious Total, serious adverse events | 3 / 13 |
Outcome results
Primary
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.
Time frame: up to 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eltrombopag | Proportion of Participants With Platelet Response | 0.23 proportion of participants |
Secondary
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.
Time frame: Weeks 2, 6 and 12
Population: Data was not collected for this outcome variable.
Secondary
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
Time frame: 12 weeks
Population: Data was not collected for this outcome variable.
Secondary
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
Time frame: 12 weeks
Population: Data was not collected for this outcome variable.
Secondary
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.
Time frame: Between weeks 1-12.
Population: Data was not collected for this outcome variable.