Avatrombopag for the Treatment of Thrombocytopenia After Donor Hematopoietic Stem Cell Transplant

Study Overview
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Brief Summary
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This phase II trial studies the side effects and how well avatrombopag works for the treatment of thrombocytopenia after donor hematopoietic stem cell transplant. Thrombocytopenia is defined as abnormally low level of platelets in the blood. Avatrombopag is a small molecule thrombopoietin receptor agonist which stimulates thrombopoietin receptor leading to increase production of platelets.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine the safety and efficacy of avatrombopag for the treatment of thrombocytopenia after allogenic hematopoietic stem cell transplantation. SECONDARY OBJECTIVE: I. To identify predictors of response to avatrombopag. OUTLINE: Patients receive avatrombopag orally (PO) once daily (QD) for up to 1 year in the absence of disease progression or unacceptable toxicity. Avatrombopag will be titrated weekly until platelet count of greater than or equal to 60,000/uL is achieved and persists for 7 consecutive days, and the patient remains free from platelet transfusion. After completion of study treatment, patients are followed up weekly for 4 weeks and then monthly up to 1 year.

Official Title
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A Phase II Trial of Avatrombopag for the Treatment of Thrombocytopenia After Allogeneic Hematopoietic Stem Cell Transplant

Conditions
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Platelet Disorder

Intervention / Treatment
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* Drug: Avatrombopag


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Failure to engraft platelets by day 30 (D30) after hematopoietic cell transplantation (HCT) defined as: Platelet count less than 20,000/uL and patient is still dependent on platelet transfusion support Patient must be able to start treatment with avatrombopag within 30-60 days following transplant Able to provide written informed consent from patient or legal representative Exclusion Criteria: Serious uncontrolled infections Steroid refractory graft versus host disease (GVHD) Patients with thrombotic microangiopathy Pregnant or lactating women Creatinine clearance < 30 ml/min Active thromboembolism requiring anticoagulation Unable to understand the investigational nature of the study or provide informed consent Evidence of disease relapse by flow cytometry of chimerisms Concomitant use of other thrombopoietin receptor agonists (TPO-RA) medication during the treatment phase of the study or two weeks prior to enrollment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (avatrombopag)<br>Patients receive avatrombopag PO QD for up to 1 year in the absence of disease progression or unacceptable toxicity. Avatrombopag will be titrated weekly until platelet count of greater than or equal to 60,000/uL is achieved and persists for 7 consecutive days, and the patient remains free from platelet transfusion. | Drug: Avatrombopag<br>* Given PO<br>* Other names: YM 477;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events of avatrombopag treatment | Toxicities will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version (v).5 standard toxicity grading. Frequency and other descriptive statistics will be used to present the toxicity pattern. | Up to 30 days after the last dose | 
| Failure rate of platelet recovery | The proportion will be provided with 95% exact binomial confidence interval. | At day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Independence from platelet transfusion |  | Up to 1 year | 
| Duration of platelet response | Will be presented in a descriptive manner. | Up to 1 year | 
| Platelet count >= 50,000/uL for 7 consecutive days without transfusion support |  | Up to 1 year | 
| Duration of exposure to avatrombopag | Will be presented in a descriptive manner. | Up to 1 year | 
| Incidence of adverse events associated with avatrombopag treatment |  | Up to 30 days after last dose | 
| Transplant-related mortality |  | At day 100 and 1 year post-hematopoietic stem cell transplant (HCT) | 
| Progression-free survival (PFS) of underlying malignant hematologic disorder | The method of Kaplan-Meier will be used to estimate PFS. | From the time of HCT to progression and death, assessed up to 1 year | 
| Overall survival (OS) | The method of Kaplan-Meier will be used to estimate OS. | From the time of HCT to death from any cause, assessed up to 1 year |