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

Primary Purpose

Aplastic Anemia, Drug Effect

Status

Completed

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Tacrolimus

Placebo (for Tacrolimus)

About this trial

This is an interventional treatment trial for Aplastic Anemia

Eligibility Criteria

14 Years - 85 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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;

Sites / Locations

Peking union medical college hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Eltrombopag

Eltrombopag + Tacrolimus

Arm 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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

ORR at 3 Months

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

The change in hematology values ( haemoglobin) were evaluated

Changes in Platelet in the Absence of Platelet Transfusion

The change in hematology values (platelet) were evaluated

Duration of hematologic response

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

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.

Full Information

NCT ID

NCT04403321

First Posted

May 21, 2020

Last Updated

January 17, 2023

Sponsor

Peking Union Medical College Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04403321

Brief Title

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

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Completed

Study Start Date

July 1, 2020 (Actual)

Primary Completion Date

July 30, 2022 (Actual)

Study Completion Date

July 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Peking Union Medical College Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Aplastic Anemia, Drug Effect

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

114 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Eltrombopag

Arm Type

Placebo Comparator

Arm Description

Arm Title

Eltrombopag + Tacrolimus

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Tacrolimus

Other Intervention Name(s)

experimental

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo (for Tacrolimus)

Other Intervention Name(s)

control

Intervention Description

placebo will be given at 1mg bid.

Primary Outcome Measure Information:

Title

ORR at 6 Months

Description

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

Time Frame

Week 26

Secondary Outcome Measure Information:

Title

ORR at 3 Months

Description

ORR will be calculated after 3 months of treatment by measuring platelet, reticulocyte, neutrophil and transfusion independence.

Time Frame

Week 14

Title

Changes in Haemoglobin in the Absence of Red Blood Cells Transfusion

Description

The change in hematology values ( haemoglobin) were evaluated

Time Frame

Week 26

Title

Changes in Platelet in the Absence of Platelet Transfusion

Description

The change in hematology values (platelet) were evaluated

Time Frame

Week 26

Title

Duration of hematologic response

Description

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

Time Frame

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

Title

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

Description

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

14 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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;

Facility Information:

Facility Name

Peking union medical college hospital

City

Beijing

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

individual participant data would be accepted upon request

IPD Sharing Time Frame

10 years

IPD Sharing Access Criteria

email request

Learn more about this trial

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

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