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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Platelet Disorder
• Intervention / Treatment: Drug: Avatrombopag

Detailed Description

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
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (avatrombopag); 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; Given PO; Other Names: Doptelet; E5501; AKR-501; AS 1670542; YM 477

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ayman Saad
• Collaborators: Sobi, Inc.
• Investigators: Principal Investigator: Ayman Saad, MB/BCH, Ohio State University Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• The Jamesline

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2022
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: March 16, 2020
• First Submitted That Met QC Criteria: March 16, 2020
• First Posted (Actual): March 18, 2020

Study Record Updates

• Last Update Posted (Actual): December 9, 2021
• Last Update Submitted That Met QC Criteria: November 26, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Thrombocytopenia; Blood Platelet Disorders
• Other Study ID Numbers: OSU-19328; NCI-2020-01035 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No