Clinical trial NCT05090384: Pediatric GVHD Low Risk Steroid Taper Trial
Official title: Serial Response and Biomarker-Guided Steroid Taper for Children With GVHD
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
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
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2021-10-22
Enrollment: 50
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Proportion of CR, VGPR, or PR on day 28 with low cumulative steroid exposure
timeFrame: study day 28
Secondary outcomes:
measure: Treatment response by day 28
timeFrame: study day 28
measure: Serious infection rate
timeFrame: study day 90
measure: Overall survival at 6 months
timeFrame: 6 months
measure: Overall survival at 12 months
timeFrame: 12 months
measure: Cumulative incidence of Non-Relapse Mortality (NRM) at 6 months
timeFrame: 6 months
measure: Cumulative incidence of Non-Relapse Mortality (NRM) at 12 months
timeFrame: 12 months
measure: Relapse rate at 6 months
timeFrame: 6 months
measure: Relapse rate at 12 months
timeFrame: 12 months
measure: Cumulative incidence of chronic GVHD
timeFrame: 12 months
measure: Cumulative steroid dose at study day 28
timeFrame: study day 28
measure: Cumulative steroid dose at study day 90
timeFrame: study day 90
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Washington
country: United States
facility: Children's National Hospital
state: District of Columbia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Boston
country: United States
facility: Boston Children's Hospital Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Texas Children's Hospital, Baylor College of Medicine
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin / Children's Wisconsin
state: Wisconsin
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: John E Levine, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Healthcare of Atlanta, Emory University School of Medicine
name: Muna Qayed, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: