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

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ClinicalTrials.gov Identifier: NCT04403321
Recruitment Status : Not yet recruiting
First Posted : May 27, 2020
Last Update Posted : June 16, 2020
Sponsor:
Information provided by (Responsible Party):
Bing Han, Peking Union Medical College Hospital

Brief Summary:
This is a randomized, open-label, phase II study to compare the efficacy of eltrombopag combined with tacrolimus//Cyclosporin A 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//Cyclosporin A. 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. Tacrolimus will be given at 1mg bid with the target concentration to be 5-10 ng/ml throughout the study. Cyclosporin A will be give at the target comcentration to be 100-150ng/ml. 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).

Condition or disease Intervention/treatment Phase
Aplastic Anemia Drug Effect Drug: Tacrolimus Drug: Placebo (for Tacrolimus) Drug: Cyclosporin A Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Eltrombopag + Tacrolimus/Cyclosporin A in Chinese Refractory or Relapsed Aplastic Anemia Patients
Estimated Study Start Date : July 1, 2020
Estimated Primary Completion Date : May 30, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: 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.
Drug: Placebo (for Tacrolimus)
placebo will be given at 1mg bid.
Other Name: control

Experimental: 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. Tacrolimus will be given at 1mg bid with the target concentration to be 5-10 ng/ml throughout the study.
Drug: Tacrolimus
Tacrolimus will be given at 1mg bid with the target concentration to be 5-10 ng/ml.
Other Name: experimental

Experimental: Eltrombopag + Cyclosporin A
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. Cyclosporin A will be given started with 100mg bid with the target concentration to be 100-150 ng/ml throughout the study.
Drug: Cyclosporin A
Cyclosporin A will be given started with 100mg bid with the target concentration to be 100-150 ng/ml throughout the study.
Other Name: experimental




Primary Outcome Measures :
  1. ORR at 6 Months [ Time Frame: Week 26 ]
    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 :
  1. ORR at 3 Months [ Time Frame: Week 14 ]
    ORR will be calculated after 3 months of treatment by measuring platelet, reticulocyte, neutrophil and transfusion independence.

  2. Changes in Haemoglobin in the Absence of Red Blood Cells Transfusion [ Time Frame: Week 26 ]
    The change in hematology values ( haemoglobin) were evaluated

  3. Changes in Platelet in the Absence of Platelet Transfusion [ Time Frame: Week 26 ]
    The change in hematology values (platelet) were evaluated

  4. Frequency and volume of Platelet and Red Blood Cells Transfusions [ Time Frame: Week 26 ]
    Platelet or RBC transfusions will be based on physician's subjective judgement. Platelet transfusion will be done if the platelet count is less than 10×10^9/liter (L) with significant bleeding tendency or the platelet count is less than 20×10^9/L with pyrexia. RBC transfusion will be done to keep the hemoglobin concentration at over 7 g/dL or in the presence of clinical symptoms such as dyspnea.

  5. Duration of hematologic response [ Time Frame: by 6 months (all patients), at 24 months (responders only) ]
    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

  6. Percentage of patients with clonal evolution to myelodysplasia, PNH, acute leukemia [ Time Frame: 12 months ]
    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.



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Ages Eligible for Study:   16 Years to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04403321


Contacts
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Contact: Bing Han +8601069151235 ext +8601069151235 hanbing1910@sina.com

Locations
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China
Peking union medical college hospital
Beijing, China
Sponsors and Collaborators
Peking Union Medical College Hospital
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Responsible Party: Bing Han, Professor, Peking Union Medical College Hospital
ClinicalTrials.gov Identifier: NCT04403321    
Other Study ID Numbers: ELT-1
First Posted: May 27, 2020    Key Record Dates
Last Update Posted: June 16, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: individual participant data would be accepted upon request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: 10 years
Access Criteria: email request

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Anemia
Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
Cyclosporine
Tacrolimus
Cyclosporins
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents