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

Ayman Saad

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Conditions

Platelet Disorder

Interventions

AvatrombopagDRUG

Given PO

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: Up to 30 days after the last dose

Failure rate of platelet recovery

The proportion will be provided with 95% exact binomial confidence interval.

Time frame: At day 90

Secondary Outcomes

Independence from platelet transfusion

Time frame: Up to 1 year

Duration of platelet response

Will be presented in a descriptive manner.

Time frame: Up to 1 year

Platelet count >= 50,000/uL for 7 consecutive days without transfusion support

Time frame: Up to 1 year

Duration of exposure to avatrombopag

Will be presented in a descriptive manner.

Time frame: Up to 1 year

Incidence of adverse events associated with avatrombopag treatment

Time frame: Up to 30 days after last dose

Transplant-related mortality

Time frame: 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.

Data from ClinicalTrials.gov

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