Avatrombopag for the Treatment of Thrombocytopenia After Donor Hematopoietic Stem Cell Transplant
Primary Purpose
Platelet Disorder
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Avatrombopag
Sponsored by
About this trial
This is an interventional treatment trial for Platelet Disorder
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (avatrombopag)
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Failure rate of platelet recovery
The proportion will be provided with 95% exact binomial confidence interval.
Secondary Outcome Measures
Independence from platelet transfusion
Duration of platelet response
Will be presented in a descriptive manner.
Platelet count >= 50,000/uL for 7 consecutive days without transfusion support
Duration of exposure to avatrombopag
Will be presented in a descriptive manner.
Incidence of adverse events associated with avatrombopag treatment
Transplant-related mortality
Progression-free survival (PFS) of underlying malignant hematologic disorder
The method of Kaplan-Meier will be used to estimate PFS.
Overall survival (OS)
The method of Kaplan-Meier will be used to estimate OS.
Full Information
NCT ID
NCT04312789
First Posted
March 16, 2020
Last Updated
November 26, 2021
Sponsor
Ayman Saad
Collaborators
Sobi, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04312789
Brief Title
Avatrombopag for the Treatment of Thrombocytopenia After Donor Hematopoietic Stem Cell Transplant
Official Title
A Phase II Trial of Avatrombopag for the Treatment of Thrombocytopenia After Allogeneic Hematopoietic Stem Cell Transplant
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Withdrawn
Why Stopped
Drug availability
Study Start Date
December 2022 (Anticipated)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
December 31, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Ayman Saad
Collaborators
Sobi, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Platelet Disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (avatrombopag)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Avatrombopag
Other Intervention Name(s)
AKR-501, AS 1670542, Doptelet, E5501, YM 477
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Incidence of adverse events of avatrombopag treatment
Description
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
Title
Failure rate of platelet recovery
Description
The proportion will be provided with 95% exact binomial confidence interval.
Time Frame
At day 90
Secondary Outcome Measure Information:
Title
Independence from platelet transfusion
Time Frame
Up to 1 year
Title
Duration of platelet response
Description
Will be presented in a descriptive manner.
Time Frame
Up to 1 year
Title
Platelet count >= 50,000/uL for 7 consecutive days without transfusion support
Time Frame
Up to 1 year
Title
Duration of exposure to avatrombopag
Description
Will be presented in a descriptive manner.
Time Frame
Up to 1 year
Title
Incidence of adverse events associated with avatrombopag treatment
Time Frame
Up to 30 days after last dose
Title
Transplant-related mortality
Time Frame
At day 100 and 1 year post-hematopoietic stem cell transplant (HCT)
Title
Progression-free survival (PFS) of underlying malignant hematologic disorder
Description
The method of Kaplan-Meier will be used to estimate PFS.
Time Frame
From the time of HCT to progression and death, assessed up to 1 year
Title
Overall survival (OS)
Description
The method of Kaplan-Meier will be used to estimate OS.
Time Frame
From the time of HCT to death from any cause, assessed up to 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ayman Saad, MB/BCH
Organizational Affiliation
Ohio State University Comprehensive Cancer Center
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://cancer.osu.edu
Description
The Jamesline
Learn more about this trial
Avatrombopag for the Treatment of Thrombocytopenia After Donor Hematopoietic Stem Cell Transplant
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