Pediatric GVHD Low Risk Steroid Taper Trial

NCT05090384 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: GCO 21-0541
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 11

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).

Conditions

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

Keywords

acute Graft vs Host Disease; aGVHD; Pediatric; steroid taper; MAP; allogeneic hematopoietic stem cell transplantation

Outcome Measures

Primary Outcomes (1)

• Proportion of CR, VGPR, or PR on day 28 with low cumulative steroid exposure

  Proportion of patients with low-risk GVHD (Minnesota standard risk/Ann Arbor 1) who are in CR, VGPR or PR on day 28 and whose cumulative prednisone (or other steroid equivalent) exposure during the first four weeks of treatment is ≤13.5 mg/kg and who have had no intervening additional GVHD therapy for those in CR or VGPR. Complete Response (CR): All evaluable organs (skin, liver, GI tract) stage 0. Very Good Partial Response (VGPR): Any response that approximates a CR with the exception of rash \<25% body surface area. Partial Response (PR): An improvement in one or more organ involved with GVHD symptoms without worsening in others.

  study day 28

Secondary Outcomes (11)

• Treatment response by day 28

  study day 28

• Serious infection rate

  study day 90

• Overall survival at 6 months

  6 months

• Overall survival at 12 months

  12 months

• Cumulative incidence of Non-Relapse Mortality (NRM) at 6 months

  6 months

Study Arms (1)

Steroid Taper

EXPERIMENTAL

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

Drug: Prednisone

Interventions

Prednisone 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

Steroid Taper

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• John Levine: lead

Study Sites (11)

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

Children's National Hospital

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Boston Children's Hospital Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37235, United States

Location

Texas Children's Hospital, Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin / Children's Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

The Hospital for Sick Children

Toronto, Ontario, M5S, Canada

Location

MeSH Terms

Interventions

Prednisone

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• John E Levine, MD, MS

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Muna Qayed, MD, MS

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Internal Medicine and Pediatrics, Director of BMT Clinical Research

Model Details: 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

Study Record Dates

• First Submitted: October 12, 2021
• First Posted: October 22, 2021
• Study Start: October 20, 2022
• Primary Completion: March 27, 2025
• Study Completion: March 1, 2026
• Last Updated: May 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (10)