MAP-guided Preemptive Therapy of aGvHD by Ruxolitinib

Study Overview
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Brief Summary
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The goal of this observation study is to test in patients undergoing allogeneic hemopoietic stem-cell transplantation (allo-HSCT). The main question it aims to answer is: • Effect of MAGIC algorithm probability guided preemption of aGVHD with ruxolitinib on prevention of severe aGVHD. Participants will take ruxolitinib with the dose of 5mg bid for 28 days. If no signs of aGvHD, the dose of ruxolitinib is gradually tapered within the following 16 days. Researchers will compare patients who don't receive preemption of aGVHD with ruxolitinib to see if there is an improvement in severe aGVHD.

Official Title
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The MAGIC Algorithm Probability Guided Preemption of Steroid-refractory Graft-versus-host Disease With Ruxolitinib

Conditions
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GVHD, Acute Stem Cell Transplant Complications

Intervention / Treatment
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* Drug: Ruxolitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any donor type (e.g., related, unrelated, haplo) or stem cell source (bone marrow, peripheral blood, cord blood). Any conditioning regimen (non-myeloablative, myeloablative, or reduced intensity) is acceptable. GVHD prophylaxis must include a calcineurin inhibitor combined with post transplant cyclophosphamide. The use of serotherapy to prevent GVHD (e.g., antithymocyte globulin) prior to day 3 post-HCT is permitted Direct bilirubin must be <2 mg/dL unless the elevation is known to be due to Gilbert syndrome within 3 days prior to enrollment. ALT/SGPT and AST/SGOT must be <5 x the upper limit of the normal range within 3 days prior to enrollment. Signed and dated written informed consent obtained from patient or legal representative. Exclusion Criteria: Patients who develop acute GVHD prior to start of study drug Patients at very high risk for relapse post HCT as defined by very high disease risk index Patients participating in a clinical trial where prevention of GVHD is the primary endpoint Uncontrolled active infection (i.e., progressive symptoms related to infection despite treatment or persistently positive microbiological cultures despite treatment or any other evidence of severe sepsis) Patients who are pregnant Patients on dialysis within 7 days of enrollment Patients requiring ventilator support or oxygen supplementation exceeding 40% FiO2 within 14 days of enrollment. Patients receiving investigational agent within 30 days of enrollment. However, the Principal Investigator (PI) may approve prior use of an investigational agent if the agent is not expected to interfere with the safety or the efficacy of ruxolitinib

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 60 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruxolitinib<br>Ruxolitinib is asministrated with the dose of 5mg bid for 28 days. If no signs of aGvHD, the dose of ruxolitinib is gradually tapered within the following 16 days. | Drug: Ruxolitinib<br>* Ruxolitinib is asministrated with the dose of 5mg bid for 28 days. If no signs of aGvHD, the dose of ruxolitinib is gradually tapered within the following 16 days.<br>|
| No Intervention: Control<br>Patients assigned to the control group are treated based on symptom-triggered aGvHD therapy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of High Risk Patients Who Develop Grade III or IV aGvHD | Number of High Risk Patients Who Develop Grade III or IV aGvHD by day 100 post HCT | Day 100 post HCT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Non-relapse Mortality (NRM) | Number of participants with NRM - deaths which could not be attributed to disease relapse or progression. Nonrelapse mortality defined as death without prior relapse at 6 months | 6 months | 
| Number of Participants With Chronic GVHD Requiring Systemic Steroid Treatment | Number of participants with chronic GVHD requiring systemic steroid treatment. Chronic GVHD Requiring Systemic Steroid Treatment: defined as the development of symptoms of chronic GVHD according to NIH Consensus Criteria that require treatment with oral or intravenous corticosteroids at the end of 1 year and 2 years | 1 year and 2 years | 
| GvHD free and relapse free survival | Survival of patients without grade 3 or 4 aGvHD or disseminated cGvHD or relapse of disease at end of 1 year post HCT at the end of 1 year and 2 years | 1 year and 2 years | 
| Progression-free survival | Progression-free survival of this group of patients at the end of 1 year and 2 years | 1 year and 2 years | 
| Overall survival | Overall survival of this group of patients at the end of 1 year and 2 years | 1 year and 2 years | 
| Number of Participants With Relapse | Number of participants with relapse at one year and 2 years. Relapse defined as recurrence of disease that required transplant. | 1 year and 2 years | 
| Number of Participants With Serious Infections | Number of participants with serious infections (defined as grade 3 by the Blood and Marrow Transplant Clinical Trials Network). Serious Infection: Defined as bacterial, fungal, viral or parasitic infections that required oral or intravenous treatments such as antibiotics | 1 year and 2 years | 
| cytomegalovirus (CMV) reactivation | Number of participants with cytomegalovirus (CMV) reactivation at the end of 1 year and 2 years. CMV reactivation was defined as the presence of DNA copies exceeding 10^3/ml in plasma. | 1 year and 2 years | 
| grade 2 or higher hemorrhagic cystitis | Number of participants with grade 2 or higher hemorrhagic cystitis at the end of 1 year and 2 years, which was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0). | 1 year and 2 years | 
| MAGIC algorithm probability (MAP) change | The change in the patient's MAGIC algorithm probability (MAP) at each time | Day 28 post HCT |