Pediatric GVHD Low Risk Steroid Taper Trial

NCT ID: NCT05090384

Last Updated: 2025-05-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-20
• Study Completion Date: 2026-03-31

Brief Summary

The standard treatment for acute graft-vs-host disease (GVHD) is to suppress the activity of the donor immune cells using steroid medications such as prednisone. Although most GVHD, especially in children, responds well to treatment, sometimes (around 1/3 of the time) there is either no response to steroids or the response does not last. In those cases, the GVHD can become dangerous and even life-threatening. Unfortunately, doctors cannot predict who will have a good response to treatment based on symptom severity or initial response to steroids. As a result, nearly all children who develop GVHD are treated with long courses of high dose steroids even though that means many patients receive more treatment than they probably need. Steroid treatment can cause short-term complications like infections, high blood sugar, high blood pressure, muscle weakness, depression, anxiety, and problems sleeping and long-term complications like bone damage, cataracts in the eyes, and decreased growth. The risk of these complications increases with higher doses of steroids and longer treatment. It is important to find ways to decrease the steroid treatment in patients who do not need long courses.

The doctors conducting this research have developed a blood test (GVHD biomarkers) that predicts whether a patient will respond well to steroids. The study team found that children who have low GVHD biomarkers at the start of treatment and for the first two weeks of treatment have a very high response rate to steroids. In this study, the study team will monitor GVHD symptoms and biomarkers during treatment and taper steroids quickly in patients who have GVHD that is expected to respond very well to treatment. The study team will assess how many patients respond well to lower steroid dosing and what steroid complications develop. The study team will also use surveys to obtain the patient's own assessment of their quality of life (down to age 5 years).

Detailed Description

Pediatric patients with Minnesota standard risk GVHD that is also Ann Arbor 1 by biomarkers will begin treatment at 0.5 mg/kg/d prednisone (or other steroid equivalent). Patients with favorable clinical responses and biomarker scores at weeks 1 and 2 will have their steroid doses tapered quickly on a weekly basis for four weeks. Patients whose GVHD does not respond or have unfavorable biomarker scores will have their steroid doses increased and be removed from study treatment. The primary endpoint is the proportion of patients whose cumulative steroid dose for the first four weeks is less than half of standard dosing.

Conditions

Acute Graft vs Host Disease; Allogeneic Bone Marrow Transplantation; Adverse Effects

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Steroid Taper

All enrolled patients start on the same dose of steroids for treatment of GVHD, blood samples are taken at week 1 and 2 post study start and biomarkers plus clinical response determines how steroid treatment is continued

Group Type: EXPERIMENTAL

Prednisone

Intervention Type: DRUG

Prednisone starting dose of 0.5 mg/kg; for patients who respond clinically and continue to have low biomarkers will be tapered rapidly; those that are not clinically responding or whose biomarkers increase will be treated per their treating physicians plan or by standard of care

Interventions

Prednisone

Prednisone starting dose of 0.5 mg/kg; for patients who respond clinically and continue to have low biomarkers will be tapered rapidly; those that are not clinically responding or whose biomarkers increase will be treated per their treating physicians plan or by standard of care

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Newly diagnosed GVHD that meets criteria for Minnesota standard risk (see section 9.0) except isolated skin rash <25% body surface area without other manifestations.
• Ann Arbor 1 GVHD by biomarkers
• GVHD not previously treated systemically (topical therapies and non-absorbed steroids are allowed)
• Any donor type, HLA-match, conditioning regimen is acceptable
• Age 0-21 years at the time of screening
• Signed and dated written informed consent obtained from patient or legal representative and assent from pediatric patients capable of providing assent

Exclusion Criteria

• Patients treated for GVHD with >0.5 mg/kg/day prednisone for any duration or any steroid treatment for GVHD for more than 2 days prior to screening.
• Patients receiving corticosteroids >0.1 mg/kg prednisone (or other steroid equivalent) for any indication within 7 days before the onset of acute GVHD except for adrenal insufficiency, premedication for transfusions/IV medications, or intermittent use for symptom control such as nausea/vomiting
• Relapsed, progressing, or persistent malignancy or other condition (e.g., known declining donor chimerism) requiring withdrawal of systemic immune suppression or donor leukocyte infusion (DLI)
• Patients with uncontrolled infection (i.e., progressive symptoms related to infection despite treatment, persistently positive microbiological cultures despite treatment, viral reactivations unresponsive to treatment, or any other evidence of severe infection)
• A clinical presentation resembling de novo chronic GVHD or overlap syndrome developing before or present at the time of enrollment
• Patients who are pregnant
• Patients requiring mechanical ventilation or cardiac pressor support

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

John Levine

OTHER

Sponsor Role: lead

Responsible Party

John Levine

Professor of Internal Medicine and Pediatrics, Director of BMT Clinical Research

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

John E Levine, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Muna Qayed, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Children's Healthcare of Atlanta, Emory University School of Medicine

Locations

Children's Hospital of Los Angeles

Los Angeles, California, United States

Children's National Hospital

Washington D.C., District of Columbia, United States

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

Boston Children's Hospital Dana Farber Cancer Institute

Boston, Massachusetts, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Texas Children's Hospital, Baylor College of Medicine

Houston, Texas, United States

Medical College of Wisconsin / Children's Wisconsin

Milwaukee, Wisconsin, United States

The Hospital for Sick Children

Toronto, Ontario, Canada

Countries

United States; Canada

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

GCO 21-0541

Identifier Type: -

Identifier Source: org_study_id