Avatrombopag for Platelet Recovery Post-UCBT in Patients With Bone Marrow Failure Disease (AVA)

Efficacy and Safety of Avatrombopag for Platelet Recovery After Unrelated Cord Blood Transplantation in Patients With Bone Marrow Failure Disease: a Single-center, Single-arm, Phase II Trial

To evaluate the efficacy and safety of Avatrombopag for platelet recovery after unrelated cord blood transplantation (UCBT) in patients with bone marrow failure disease

Study Overview

• Status: Recruiting
• Conditions: Platelet Recovery After Umbilical Cord Blood Transplantation
• Intervention / Treatment: Drug: Avatrombopag

Detailed Description

Persistent thrombocytopenia is a common complication after umbilical cord blood transplantation (UCBT), which necessitates platelet transfusion and leads to increased transplant-related mortality. This is a single-center, single-arm, phase II clinical trial aimed at evaluating the efficacy and safety of Avatrombopag for platelet recovery after UCBT in patients with bone marrow failure disease (BMFD). The study was conducted in patients diagnosed with BFMD and receiving UCBT. After the subjects signed and informed and qualified, they received Avatrombopag treatment from the first day to the 28th day after transplantation. In this study, the cumulative of platelet implantation rate at 28 days after transplantation was used as the main therapeutic index, and 40 patients were planned to be enrolled.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Xiaoyu Zhu, Ph.D; Phone Number: 15255456091; Email: xiaoyuz@ustc.edu.cn
• Study Contact Backup: Name: Aijie Huang, M.D; Phone Number: 15221056490; Email: huangaijie@mail.ustc.edu.cn

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230036
      • Recruiting
      • The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital)
      • Contact: Aijie Huang, M.D; Phone Number: 15221056490; Email: huangaijie@mail.ustc.edu.cn
      • Contact: Xiaoyu Zhu, ph.D; Phone Number: 15255456091; Email: xiaoyuz@ustc.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients diagnosed with bone marrow failure and receiving umbilical cord blood transplantation

Description

Inclusion Criteria:

• Age ≥12 years old, male or female;
• Patients diagnosed with bone marrow failure disease including aplastic anemia (AA), Fanconi anemia (FA), paroxysmal nocturnal hemoglobinuria (PNH) and undergoing UCBT;
• ECOG score ≤2;
• Voluntary participation in this clinical trial, patients fully understand the trial content and sign the informed consent；

Exclusion Criteria:

• Pregnant or lactating women；
• Known allergy to Avatrombopag;
• A history of severe thrombotic events or known risk factors for thrombosis or active thromboembolism requiring anticoagulation;
• A history of platelet dysfunction or bleeding prone disease or severe bleeding (requiring more than 2 units of red blood cell infusion or a hematocrit drop of ≥10%) within 7 days prior to screening;
• Chronic active hepatitis B and C;
• Repeat or multiple transplantation or multiple organ transplantation;
• HIV positive, EBV-DNA positive, CMV-DNA positive;
• Have severe infection or complicated with serious heart, liver, lung, kidney, neurological or metabolic diseases;
• A serious adverse event (Level 4 or 5) as defined by the Standard General Terminology for Adverse Events Version 4.0 occurred during the pre-treatment period;
• Participants participate in another clinical study with any exploratory drug or device within 30 days prior to baseline visit; Observational studies are allowed;
• Subjects with cognitive impairment or uncontrolled mental illness;
• Subjects and/or authorized family members to refuse treatment with Avatrombopag;
• Those who are judged by the researchers as not suitable for inclusion (such as accompanying medical history, which may affect the safety of the subjects or it is estimated that the treatment cannot be adhered to due to financial problems).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Avatrombopag group; The duration of the study is 4 weeks, from +1 day to +28 days after UCBT, patients will be given Avatrombopag with a recommended dose of 40mg per day. After 28 days of administration, the patients may continue, change or discontinue medication based on the patients' platelet status.	Drug: Avatrombopag; Indications for drug reduction and withdrawal: excluding blood transfusion factors, the reduction will be 20mg/d when PLT≥50×10^9/L; Drug administration will be stopped when PLT≥100×10^9/L.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of platelet engraftment	Platelet engraftment is defined as independence from platelet transfusion for at least 7 days with a platelet count of more than ≥20 × 10^9/L.	28 days
The cumulative incidence of platelet engraftment at 28 days after transplantation	Platelet engraftment is defined as independence from platelet transfusion for at least 7 days with a platelet count of more than ≥20 × 10^9/L.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The cumulative incidence of platelet recovery rate at 28 days after transplantation	Platelet recovery was defined as independence from platelet transfusion for at least 7 days with a platelet count of more than ≥50×10^9/L.	28 days
Total platelet transfusion during 4 weeks of treatment	Total platelet transfusion during 4 weeks of treatment	28 days
neutrophil reconstitution	neutrophil engraftment time was defined as the first of three consecutive days during which the neutrophil count was at least 0.5×10^9/L.	28 days
erythroid reconstitution	RBC engraftment time was defined as the first day of achieving a reticulocyte count greater than 1% for 3 consecutive days.	28 days
Megakaryocyte levels in bone marrow smears 4 weeks after treatment	Megakaryocyte levels in bone marrow smears 4 weeks after treatment	4 weeks
Time of platelet recovery	Platelet count ≥50×10^9/L for 3 consecutive days without platelet transfusions for 7 consecutive days	100 days
Time of platelet ≥100×10^9/L.	Platelet count ≥100×10^9/L for 3 consecutive days without platelet transfusions for 7 consecutive days	100 days

Collaborators and Investigators

• Sponsor: Anhui Provincial Hospital
• Investigators: Principal Investigator: Xiaoyu Zhu, Ph.D, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital)

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2023
• Primary Completion (Estimated): January 31, 2025
• Study Completion (Estimated): February 28, 2025

Study Registration Dates

• First Submitted: March 24, 2023
• First Submitted That Met QC Criteria: April 19, 2023
• First Posted (Actual): April 21, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 30, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Avatrobopag
• Additional Relevant MeSH Terms: Cytopenia; Hematologic Diseases; Bone Marrow Diseases; Bone Marrow Failure Disorders; Pancytopenia
• Other Study ID Numbers: AVA&MDS-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No