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).
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
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
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
...and 1 more locations
Number of Participants Who Were Responders (CR, VGPR, or PR) on Day 28 With Low Cumulative Steroid Exposure
Number of participants who were responders. Responders are 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.
Time frame: study day 28
Number of Participants Who Achieved a Treatment Response by Day 28
Number of participants who achieve a treatment response by day 28 of treatment. Treatment responses are defined as complete response (CR), very good partial response (VGPR), or partial response (PR). For a response to be scored as CR, VGPR, or PR on day 28, the patient must be in response on day 28 and have had no intervening systemic therapy for acute GVHD other than steroids.
Time frame: study day 28
Number of Participants Who Developed Serious Infection
Number of patients who develop serious infections (viral, bacterial, fungal, parasitic) Serious infections are defined using the standardized criteria widely used for clinical trials at academic BMT centers, such as life-threatening fungal infections or hemorrhagic cystitis from BK viral infection and include clinically significant CMV infections that require anti-viral treatment regardless of end-organ damage, given the toxicity of such treatments. Serious infections include any viral, bacterial, fungal or parasitic infections that requires systemic treatment.
Time frame: study day 90
Number of Participants Alive at 6 Months
Overall survival assessed by number of participants alive at 6 months OS is defined as the time from the first dose of study treatment to the date of death (whatever the cause).
Time frame: 6 months
Overall Survival at 12 Months
Overall survival at 12 months OS is defined as the time from the first dose of study treatment to the date of death (whatever the cause).
Time frame: 12 months
Number of Participants Who Had Non-Relapse Mortality (NRM) at 6 Months
Number of Participants who had NRM at 6 months Survival will be tracked during the study, any deaths will be collected. Any death that occurs after hematopoietic stem cell transplantation (HCT) not attributable to relapse of the underlying disease will be considered a non-relapse death.
Time frame: 6 months
Cumulative Incidence of Non-Relapse Mortality (NRM) at 12 Months
Cumulative incidence of NRM at 12 months Survival will be tracked during the study, any deaths will be collected. Any death that occurs after HCT not attributable to relapse of the underlying disease will be considered a non-relapse death.
Time frame: 12 months
Number of Participants Who Relapsed at 6 Months
Number of participants who relapsed of the underlying malignancy at 6 months.
Time frame: 6 months
Relapse Rate at 12 Months
Relapse rate at 12 months Relapse, including date of relapse, of the underlying malignancy will be reported.
Time frame: 12 months
Cumulative Incidence of Chronic GVHD
Cumulative incidence of chronic GVHD requiring systemic steroid treatment by one year from enrollment
Time frame: 12 months
Cumulative Steroid Dose at Study Day 28
Cumulative steroid dose at day 28 Steroid drug and dose is collected weekly for the first 4 weeks of study.
Time frame: study day 28
Cumulative Steroid Dose at Study Day 90
Cumulative steroid dose at day 90 Steroid drug and dose is collected weekly for the first 4 weeks of study, and bi-weekly through study day 90.
Time frame: study day 90
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