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

NCT04403321 | Completed Phase 2

• 1 other identifier: ELT-1
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• ORR at 6 Months

  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

  Week 26

Secondary Outcomes (5)

• ORR at 3 Months

  Week 14

• Changes in Haemoglobin in the Absence of Red Blood Cells Transfusion

  Week 26

• Changes in Platelet in the Absence of Platelet Transfusion

  Week 26

• Duration of hematologic response

  by 6 months (all patients), at 24 months (responders only)

• Percentage of patients with clonal evolution to myelodysplasia, PNH, acute leukemia

  12 months

Study Arms (2)

Eltrombopag

PLACEBO COMPARATOR

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.

Drug: Placebo (for Tacrolimus)

Eltrombopag + Tacrolimus

EXPERIMENTAL

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.

Drug: Tacrolimus

Interventions

Tacrolimus DRUG

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

Also known as: experimental

Eltrombopag + Tacrolimus

Placebo (for Tacrolimus) DRUG

placebo will be given at 1mg bid.

Also known as: control

Eltrombopag

Eligibility Criteria

• Age: 14 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);
• Current diagnosis of aplastic anemia by bone marrow biopsy;
• did not receive HSCT nor were HSCT candidates;
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0-2;
• 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.
• Subjects are able to understand and comply with protocol requirements and instructions and have signed and dated informed consent.

You may not qualify if:

• Congenital aplastic anemia;
• Presence of chromosomal aberration;
• Evidence of a clonal hematologic bone marrow disorder on cytogenetics;
• Have any concomitant malignancies and must be fully recovered from treatment for any other malignancy and have been disease-free for 5 years;
• AST or ALT ≥3 times the upper limit of normal;
• Serum creatinine, total bilirubin, or alkaline phosphatase \>1.5 x ULN;
• Cardiac disorder (NYHA) functional classification Grade II/III/IV;
• Past history of thromboembolic event (including anti-phospholipid antibody syndrome) and current use of anticoagulants;
• Infection not adequately responding to appropriate therapy;
• Other known or suspected underlying primary immunodeficiency;
• Prior treatment with eltrombopag, romiplostim, or any other TPO (thrombopoietin) receptor agonist;
• Pregnant or nursing (lactating) woman;

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking union medical college hospital

Beijing, China

Location

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

Tacrolimus

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 21, 2020
• First Posted: May 27, 2020
• Study Start: July 1, 2020
• Primary Completion: July 30, 2022
• Study Completion: July 31, 2022
• Last Updated: January 19, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 10 years
• Access Criteria: email request

Locations

CN (1)