MAP-guided Preemptive Therapy of aGvHD

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

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.

Study Overview

• Status: Recruiting
• Conditions: Stem Cell Transplant Complications; GVHD,Acute
• Intervention / Treatment: Drug: Methylprednisolone

• Study Type: Interventional
• Enrollment (Anticipated): 56
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jie Ji, MD; Phone Number: 86-28-85422373; Email: jieji@scu.edu.cn

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610044
      • Recruiting
      • West China Hospital of Sichuan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prevention group; 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; 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.

What is the study measuring?

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 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
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
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

Collaborators and Investigators

• Sponsor: Sichuan University

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2022
• Primary Completion (Anticipated): January 30, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: May 5, 2022
• First Submitted That Met QC Criteria: May 9, 2022
• First Posted (Actual): May 10, 2022

Study Record Updates

• Last Update Posted (Actual): May 10, 2022
• Last Update Submitted That Met QC Criteria: May 9, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: HXMAP 1.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No