Clinical trial NCT04312789: 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
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Platelet Disorder
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Sobi, Inc.
First posted: 2020-03-18
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of adverse events of avatrombopag treatment
timeFrame: Up to 30 days after the last dose
measure: Failure rate of platelet recovery
timeFrame: At day 90
Secondary outcomes:
measure: Independence from platelet transfusion
timeFrame: Up to 1 year
measure: Duration of platelet response
timeFrame: Up to 1 year
measure: Platelet count >= 50,000/uL for 7 consecutive days without transfusion support
timeFrame: Up to 1 year
measure: Duration of exposure to avatrombopag
timeFrame: Up to 1 year
measure: Incidence of adverse events associated with avatrombopag treatment
timeFrame: Up to 30 days after last dose
measure: Transplant-related mortality
timeFrame: At day 100 and 1 year post-hematopoietic stem cell transplant (HCT)
measure: Progression-free survival (PFS) of underlying malignant hematologic disorder
timeFrame: From the time of HCT to progression and death, assessed up to 1 year
measure: Overall survival (OS)
timeFrame: From the time of HCT to death from any cause, assessed up to 1 year
Other outcomes:
Locations:
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: Ayman Saad, MB/BCH
role: PRINCIPAL_INVESTIGATOR
References: