Aplastic Anemia, Drug Effect
Conditions
Brief summary
This is a randomized, open-label, phase II study to compare the efficacy of eltrombopag combined with tacrolimus to eltrombopag alone in Chinese subjects with refractory or relapsed aplastic anemia. The safety would also be evaluated. Patients would be randomized to receive eltrombopag alone or eltrombopag combined with tacrolimus. Treatment with eltrombopag will be started at 25 mg/day and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day, or the best response was achieved. Tacrolimus will be given at 1mg bid with the target trough concentration of 4-10 ng/mL throughout the study. The hematological response rate and safety will be recorded and compared at 3, 6 months and 1 year after starting the study treatment (Week 13, 26 and 52).
Interventions
DRUGTacrolimus
Tacrolimus will be given at 1mg bid with the target trough concentration to be 4-10 ng/mL.
DRUGPlacebo (for Tacrolimus)
placebo will be given at 1mg bid.
Sponsors
Peking Union Medical College Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
14 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Patient with a previous diagnosis of aplastic anemia and had no response or relapsed following at least one treatment course in a period time of ≥ 6 months of immunosuppression containing CsA or CsA+anti-thymocyte globulin (ATG); 2. Current diagnosis of aplastic anemia by bone marrow biopsy; 3. did not receive HSCT nor were HSCT candidates; 4. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-2; 5. Patient with QTcF (Fridericia's QT correction formula) at screening \<450 msec, or \<480 msec with bundle branch block, as determined via the mean of a triplicate ECG and assessed at site. 6. Subjects are able to understand and comply with protocol requirements and instructions and have signed and dated informed consent.
Exclusion criteria
1. Congenital aplastic anemia; 2. Presence of chromosomal aberration; 3. Evidence of a clonal hematologic bone marrow disorder on cytogenetics; 4. Have any concomitant malignancies and must be fully recovered from treatment for any other malignancy and have been disease-free for 5 years; 5. AST or ALT ≥3 times the upper limit of normal; 6. Serum creatinine, total bilirubin, or alkaline phosphatase \>1.5 x ULN; 7. Cardiac disorder (NYHA) functional classification Grade II/III/IV; 8. Past history of thromboembolic event (including anti-phospholipid antibody syndrome) and current use of anticoagulants; 9. Infection not adequately responding to appropriate therapy; 10. Other known or suspected underlying primary immunodeficiency; 11. Prior treatment with eltrombopag, romiplostim, or any other TPO (thrombopoietin) receptor agonist; 12. Pregnant or nursing (lactating) woman;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR at 6 Months | Week 26 | Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR) at Week 26 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Platelet in the Absence of Platelet Transfusion | Week 26 | The change in hematology values (platelet) were evaluated |
| ORR at 3 Months | Week 14 | ORR will be calculated after 3 months of treatment by measuring platelet, reticulocyte, neutrophil and transfusion independence. |
| Changes in Haemoglobin in the Absence of Red Blood Cells Transfusion | Week 26 | The change in hematology values ( haemoglobin) were evaluated |
| Duration of hematologic response | by 6 months (all patients), at 24 months (responders only) | Time from the date of the start of the first response to the date of first relapse defined as again meeting criteria for aplastic anemia |
| Percentage of patients with clonal evolution to myelodysplasia, PNH, acute leukemia | 12 months | Clonal evolution to myelodysplasia is defined as a new marrow cytogenic abnormality with or without characteristic dysplastic marrow findings. Evolution to leukemia is defined as greater than 20% peripheral blood and/or marrow blasts. Evolution to paroxysmal nocturnal hemoglobinuria (PNH) is defined as a clone at baseline \< 10% that rose to greater than 50% on study. |
Countries
China
Outcome results
None listed