MAP-guided Preemptive Therapy of aGvHD

Sponsor

Sichuan University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05368181

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
GVHD,Acute Stem Cell Transplant Complications	Drug: Methylprednisolone	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

56 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

methylprednisolonemethylprednisolone

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

May 1, 2022

Anticipated Primary Completion Date :

Jan 30, 2023

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Number of High Risk Patients Who Develop Grade III or IV aGvHD [Day 100 post HCT]
Number of High Risk Patients Who Develop Grade III or IV aGvHD by day 100 post HCT

Secondary Outcome Measures

Number of Participants Alive at 6 Months and 1 Year [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
Number of Participants With Non-relapse Mortality (NRM) [6 months and 1 year]
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.
Number of Participants With Relapse [1 year]
Number of participants with relapse at one year. Relapse defined as recurrence of disease that required transplant.
Number of Participants With Clinically Relevant GVHD States Grade II-IV GVHD [100 days]
Number of participants with clinically relevant GVHD states grade II-IV GVHD requiring systemic treatment.
Number of Participants With Chronic GVHD Requiring Systemic Steroid Treatment [1 year]
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.
Number of Participants With Serious Infections [1 year]
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.
Overall survival [1 year]
Overall survival of this group of patients at the end of 1 year
GvHD free and relapse free survival [1 year]
Survival of patients without grade 3 or 4 aGvHD or disseminated cGvHD or relapse of disease at end of 1 year post HCT

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.