Efficacy and Safety of Eltrombopag + Tacrolimus in Chinese Refractory or Relapsed Aplastic Anemia Patients

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Completed; Phase 2

Conditions: Drug Effect; Aplastic Anemia

Treatments: Drug: Placebo (for Tacrolimus); Drug: Tacrolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT04403321

ELT-1

Details and patient eligibility

About

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).

Enrollment: 114 patients

Sex: All

Ages: 14 to 85 years old

Volunteers: No Healthy Volunteers

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;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

114 participants in 2 patient groups, including a placebo group

Eltrombopag

Placebo Comparator group

Description:

Eltrombopag and the placebo would be applied. 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.

Treatment:

Drug: Placebo (for Tacrolimus)

Eltrombopag + Tacrolimus

Experimental group

Description:

Eltrombopag and tacrolimus would be applied. 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.

Treatment:

Drug: Tacrolimus