Clinical trial NCT04403321: Efficacy and Safety of Eltrombopag + Tacrolimus in Chinese Refractory or Relapsed Aplastic Anemia Patients
Official title: Efficacy and Safety of Eltrombopag + Tacrolimus in Chinese Refractory or Relapsed Aplastic Anemia Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Aplastic Anemia
Drug Effect
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2020-05-27
Enrollment: 114
Sex: ALL
Minimum age (years): 14
Maximum age (years): 85
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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;

Primary outcomes:
measure: ORR at 6 Months
timeFrame: Week 26
Secondary outcomes:
measure: ORR at 3 Months
timeFrame: Week 14
measure: Changes in Haemoglobin in the Absence of Red Blood Cells Transfusion
timeFrame: Week 26
measure: Changes in Platelet in the Absence of Platelet Transfusion
timeFrame: Week 26
measure: Duration of hematologic response
timeFrame: by 6 months (all patients), at 24 months (responders only)
measure: Percentage of patients with clonal evolution to myelodysplasia, PNH, acute leukemia
timeFrame: 12 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking union medical college hospital
Study officials:
References: