Clinical trial NCT05368181: MAP-guided Preemptive Therapy of aGvHD
Official title: The MAGIC Algorithm Probability Guided Preemption of Steroid-refractory Graft-versus-host Disease With Methylprednisolone
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: GVHD,Acute
Stem Cell Transplant Complications
Lead sponsor: Sichuan University
Sponsor class: OTHER
First posted: 2022-05-10
Enrollment: 56
Sex: ALL
Minimum age (years): 16
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: methylprednisolone
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of High Risk Patients Who Develop Grade III or IV aGvHD
timeFrame: Day 100 post HCT
Secondary outcomes:
measure: Number of Participants Alive at 6 Months and 1 Year
timeFrame: 6 months and 1 year
measure: Number of Participants With Non-relapse Mortality (NRM)
timeFrame: 6 months and 1 year
measure: Number of Participants With Relapse
timeFrame: 1 year
measure: Number of Participants With Clinically Relevant GVHD States Grade II-IV GVHD
timeFrame: 100 days
measure: Number of Participants With Chronic GVHD Requiring Systemic Steroid Treatment
timeFrame: 1 year
measure: Number of Participants With Serious Infections
timeFrame: 1 year
measure: Overall survival
timeFrame: 1 year
measure: GvHD free and relapse free survival
timeFrame: 1 year
Other outcomes:
Locations:
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
Study officials:
References: