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

NCT ID: NCT04403321

Last Updated: 2023-01-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 114 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-01
• Study Completion Date: 2022-07-31

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).

Conditions

Aplastic Anemia; Drug Effect

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Eltrombopag

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.

Group Type: PLACEBO_COMPARATOR

Placebo (for Tacrolimus)

Intervention Type: DRUG

placebo will be given at 1mg bid.

Eltrombopag + Tacrolimus

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.

Group Type: EXPERIMENTAL

Tacrolimus

Intervention Type: DRUG

Tacrolimus will be given at 1mg bid with the target trough concentration to be 4-10 ng/mL.

Interventions

Tacrolimus

Tacrolimus will be given at 1mg bid with the target trough concentration to be 4-10 ng/mL.

Intervention Type: DRUG

Placebo (for Tacrolimus)

placebo will be given at 1mg bid.

Intervention Type: DRUG

Other Intervention Names

experimental; control

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;

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Bing Han

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Peking union medical college hospital

Beijing, , China

Countries

China

Other Identifiers

ELT-1

Identifier Type: -

Identifier Source: org_study_id