Platelet Disorder
Conditions
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.
Interventions
DRUGAvatrombopag
Given PO
Sponsors
Sobi, Inc.
Ayman Saad
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events of avatrombopag treatment | Up to 30 days after the last dose | 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 | At day 90 | The proportion will be provided with 95% exact binomial confidence interval. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Platelet count >= 50,000/uL for 7 consecutive days without transfusion support | Up to 1 year | — |
| Duration of exposure to avatrombopag | Up to 1 year | Will be presented in a descriptive manner. |
| Incidence of adverse events associated with avatrombopag treatment | Up to 30 days after last dose | — |
| Independence from platelet transfusion | Up to 1 year | — |
| Progression-free survival (PFS) of underlying malignant hematologic disorder | From the time of HCT to progression and death, assessed up to 1 year | The method of Kaplan-Meier will be used to estimate PFS. |
| Overall survival (OS) | From the time of HCT to death from any cause, assessed up to 1 year | The method of Kaplan-Meier will be used to estimate OS. |
| Transplant-related mortality | At day 100 and 1 year post-hematopoietic stem cell transplant (HCT) | — |
| Duration of platelet response | Up to 1 year | Will be presented in a descriptive manner. |
Outcome results
None listed