MAP-guided Preemptive Therapy of aGvHD

Study Overview
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Brief Summary
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Acute graft versus host disease (aGvHD) is a severe and potentially fatal complication of allogeneic hematopoietic stem cell transplantation (HCT). The Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm probability (MAP) identifies patients who are at high risk for severe aGvHD as early as 7 days after HCT based on 2 serum biomarkers, suppressor of tumorigenesis 2 (ST2) and regenerating islet-derived 3α (Reg3α). Patients who consent to this study will have their blood tested weekly up to four times within the first month post HCT to determine if they are at high risk for severe GVHD based on MAP. Patients who are at high risk at any of these four tests will be treated with methylprednisolone to see if it prevents the development of severe aGvHD. Methylprednisolone starts with the dose of 2 mg/kg for 5 days. If no signs of aGvHD, the dose of methylprednisolone is gradually tapered within the following 16 days. Patients will be followed for the development of severe aGvHD for up to 3 months from the HCT and will continue to be followed at routine clinic visits for up to one year after HCT.

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

Conditions
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GVHD,Acute, Stem Cell Transplant Complications

Intervention / Treatment
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* Drug: Methylprednisolone


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 methylprednisolone.

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
Intervention Model: Single Group Assignment
Interventional Model Description: methylprednisolone
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prevention group<br>Methylprednisolone starts with the dose of 2 mg/kg for 5 days. If no signs of aGvHD, the dose of methylprednisolone is gradually taper with the following 16 days. | Drug: Methylprednisolone<br>* Methylprednisolone starts with the dose of 2 mg/kg for 5 days. If no signs of aGvHD, the dose of methylprednisolone is gradually taper with the following 16 days.<br>|

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 Alive at 6 Months and 1 Year | Overall survival - The number of that patients are still alive from the start of treatment at 6 months and 1 year | 6 months and 1 year | 
| Number of Participants With Non-relapse Mortality (NRM) | Number of participants with NRM - deaths which could not be attributed to disease relapse or progression. Non-relapse mortality defined as death without prior relapse. | 6 months and 1 year | 
| Number of Participants With Relapse | Number of participants with relapse at one year. Relapse defined as recurrence of disease that required transplant. | 1 year | 
| Number of Participants With Clinically Relevant GVHD States Grade II-IV GVHD | Number of participants with clinically relevant GVHD states grade II-IV GVHD requiring systemic treatment. | 100 days | 
| 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. | 1 year | 
| 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 | 
| Overall survival | Overall survival of this group of patients at the end of 1 year | 1 year | 
| 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 | 1 year |