Prevention of Severe Acute Graft-versus-host Disease in Pediatric Patients Using a daGOAT Model

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of ruxolitinib for prophylactic therapy of child patients who are predicted to have a high risk for developing severe acute graftversus-host disease (aGVHD) by the dynamic aGVHD Onset Anticipation Tianjin (daGOAT) model.

Detailed Description
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This study aims to prospectively evaluate the use of the daGOAT model in real-world clinical settings at the Institute of Hematology, Chinese Academy of Medical Sciences (IHCAMS).

Official Title
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A Prospective, Single-arm Clinical Trial of Prevention of Severe Acute Graft-versus-host Disease After Pediatric Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation Using a daGOAT Model

Conditions
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Transplant-Related Disorder

Intervention / Treatment
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* Drug: Ruxolitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be ≤ 16 years of age; Patients receiving human leukocyte antigen mismatched and non-cord blood allogeneic hematopoietic stem cell transplantation; Patients who can take oral medication; Patients or their guardians have to sign an informed consent form before the start of the research procedure. Exclusion Criteria: Tandem transplantation or multiple transplantations; Patients who are allergic to or cannot tolerate ruxolitinib; Mental or other medical conditions that make the patients unable to comply with the research treatment and monitoring requirements; Patients who are pregnant or cannot take appropriate contraceptive measures during treatment; Patients who are ineligible for the study due to other factors, or will bear great risk if participating in the study.

Ages Eligible for Study
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Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The group of daGOAT model prevention<br>Model-predicted high-risk patients: weight ≤ 25 kg, ruxolitinib, 2.5mg bid po until at least day 60 post-transplant and terminated after day 100; weight > 25 kg, ruxolitinib, 5mg bid po until at least day 60 post-transplant and terminated after day 100. If 'azoles' are taken concomitantly, ruxolitinib will start at half dose. If the patient tolerates ruxolitinib, the dose can be increased to 10mg bid po. Model-predicted low risk: regular aGVHD prophylactic regimens. | Drug: Ruxolitinib<br>* Model-predicted high-risk patients: weight ≤ 25 kg, ruxolitinib, 2.5mg bid po until at least day 60 post-transplant and terminated after day 100; weight > 25 kg, ruxolitinib, 5mg bid po until at least day 60 post-transplant and terminated after day 100. If 'azoles' are taken concomitantly, ruxolitinib will start at half dose. If the patient tolerates ruxolitinib, the dose can be increased to 10mg bid po. Model-predicted low risk: regular aGVHD prophylactic regimens.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe aGVHD during 100 days after transplantation according to the MAGIC criteria | Incidence of severe aGVHD after transplantation within 100 days. The medical records for each case wil be reviewed by two or three physicians to confirm the aGVHD diagnosis and grading (according to the MAGIC criteria). | 100 days after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| aGVHD in various target organs during 100 days after transplantation according to the MAGIC criteria | Incidence of aGVHD (any grade) in various target organs. The medical records for each case wil be reviewed by two or three physicians to confirm the aGVHD diagnosis and grading (according to the MAGIC criteria). | 100 days after transplantation | 
| Overall survival during 1.5 year after transplantation | Patients will be followed up at days 14, 28, 42, 60, 90, 180, 270, 360 and 540 after transplantation; data on survival will be collected. | Days 14, 28, 42, 60, 90, 180, 270, 360 and 540 after transplantation | 
| Relapse-free survival rate and relapse rate during 1.5 year after transplantation | Patients will be followed up at days 14, 28, 42, 60, 90, 180, 270, 360 and 540 after transplantation; data on relapse will be collected. | Days 14, 28, 42, 60, 90, 180, 270, 360 and 540 after transplantation | 
| Incidence of infections during 1.5 year after transplantation | Infection was defined as meeting one of the following criteria: culture-confirmed presence of bacteria or fungi in a sample collected from a sterile site; polymerase chain reaction-confirmed viremia at ≥ 5000 copies/ml for the cytomegalovirus or ≥ 10000 copies/ml for the Epstein-Barr virus; or body temperature ≥ 38 ℃ with culture-confirmed presence of pathogens from a non-sterile site. | 1.5 year after transplantation | 
| Safety of treatment during 100 days after transplantation according to the Common Terminology Criteria for Adverse Events version 5.0 | Data on adverse events of treatment will be collected. | 100 days after transplantation | 
| Total cost of treatment during 1.5 year after transplantation | Data on total cost of treatment will be collected from the medical records. | 1.5 year after transplantation |