Back to resultsPediatric GVHD Low Risk Steroid Taper Trial
Primary Purpose
Acute Graft vs Host Disease, Allogeneic Bone Marrow Transplantation, Adverse Effects
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Prednisone
Sponsored by
About this trial
This is an interventional treatment trial for Acute Graft vs Host Disease focused on measuring acute Graft vs Host Disease, aGVHD, Pediatric, steroid taper, MAP, allogeneic hematopoietic stem cell transplantation
Eligibility Criteria
Inclusion Criteria:
- Newly diagnosed GVHD that meets criteria for Minnesota standard risk except GVHD that is limited to skin rash <50% body surface area (grade I GVHD) OR isolated upper gastrointestinal tract involvement
- 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
- Performance score (Lansky/Karnofsky) ≥70%
- 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 prednisone or any steroid treatment for GVHD for more than 3 days prior to enrollment
- 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
- 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)
- Severe organ dysfunction including requirement for dialysis, mechanical ventilation, or oxygen supplementation exceeding 40% FiO2 within 7 days of enrollment
- Significant liver disease evidenced by direct bilirubin >2 mg/dl or ALT or AST >5 times the upper limit of normal
- Creatinine clearance or estimated glomerular filtration rate <30 ml/min as calculated by institutional practice
- A clinical presentation resembling de novo chronic GVHD or overlap syndrome developing before or present at the time of enrollment
- Patients who are pregnant
Sites / Locations
- Children's Hospital of Los AngelesRecruiting
- Children's Healthcare of AtlantaRecruiting
- Icahn School of Medicine at Mount SinaiRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- Children's Hospital of Philadelphia
- Vanderbilt University Medical CenterRecruiting
- The Hospital for Sick Children
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Steroid Taper
Arm 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
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Treatment response by day 28
Proportion of patients 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.
Serious infection rate
Proportion of patients who develop serious infections (viral, bacterial, fungal, parasitic as defined in protocol)
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.
Overall survival at 6 months
Overall survival at 6 months
OS is defined as the time from the first dose of study treatment to the date of death (whatever the cause).
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).
Cumulative incidence of Non-Relapse Mortality (NRM) at 6 months
Cumulative incidence of 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.
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.
Relapse rate at 6 months
Relapse rate at 6 months
Relapse, including date of relapse, of the underlying malignancy will be reported.
Relapse rate at 12 months
Relapse rate at 12 months
Relapse, including date of relapse, of the underlying malignancy will be reported.
Cumulative incidence of chronic GVHD
Cumulative incidence of chronic GVHD requiring systemic steroid treatment by one year from enrollment
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05090384
Brief Title
Pediatric GVHD Low Risk Steroid Taper Trial
Official Title
Serial Response and Biomarker-Guided Steroid Taper for Children With GVHD
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 20, 2022 (Actual)
Primary Completion Date
March 2025 (Anticipated)
Study Completion Date
March 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
John Levine
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
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
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Steroid Taper
Arm Type
Experimental
Arm 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
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
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
Primary Outcome Measure Information:
Title
Proportion of CR, VGPR, or PR on day 28 with low cumulative steroid exposure
Description
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.
Time Frame
study day 28
Secondary Outcome Measure Information:
Title
Treatment response by day 28
Description
Proportion of patients 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
Title
Serious infection rate
Description
Proportion of patients who develop serious infections (viral, bacterial, fungal, parasitic as defined in protocol)
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
Title
Overall survival at 6 months
Description
Overall survival 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
Title
Overall survival at 12 months
Description
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
Title
Cumulative incidence of Non-Relapse Mortality (NRM) at 6 months
Description
Cumulative incidence of 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
Title
Cumulative incidence of Non-Relapse Mortality (NRM) at 12 months
Description
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
Title
Relapse rate at 6 months
Description
Relapse rate at 6 months
Relapse, including date of relapse, of the underlying malignancy will be reported.
Time Frame
6 months
Title
Relapse rate at 12 months
Description
Relapse rate at 12 months
Relapse, including date of relapse, of the underlying malignancy will be reported.
Time Frame
12 months
Title
Cumulative incidence of chronic GVHD
Description
Cumulative incidence of chronic GVHD requiring systemic steroid treatment by one year from enrollment
Time Frame
12 months
Title
Cumulative steroid dose at study day 28
Description
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
Title
Cumulative steroid dose at study day 90
Description
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
10. Eligibility
Sex
All
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Newly diagnosed GVHD that meets criteria for Minnesota standard risk except GVHD that is limited to skin rash <50% body surface area (grade I GVHD) OR isolated upper gastrointestinal tract involvement
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
Performance score (Lansky/Karnofsky) ≥70%
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 prednisone or any steroid treatment for GVHD for more than 3 days prior to enrollment
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
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)
Severe organ dysfunction including requirement for dialysis, mechanical ventilation, or oxygen supplementation exceeding 40% FiO2 within 7 days of enrollment
Significant liver disease evidenced by direct bilirubin >2 mg/dl or ALT or AST >5 times the upper limit of normal
Creatinine clearance or estimated glomerular filtration rate <30 ml/min as calculated by institutional practice
A clinical presentation resembling de novo chronic GVHD or overlap syndrome developing before or present at the time of enrollment
Patients who are pregnant
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rachel Young
Phone
212-659-5605
Email
rachel.young@mssm.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Janna Baez
Phone
212-241-0590
Email
janna.baez@mssm.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John E Levine, MD, MS
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Muna Qayed, MD, MS
Organizational Affiliation
Children's Healthcare of Atlanta, Emory University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Hospital of Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paibel Aguayo-Hiraldo, MD
Phone
323-361-1455
Email
paguayohiraldo@chla.usc.edu
First Name & Middle Initial & Last Name & Degree
Paibel Aguayo-Hiraldo
Facility Name
Children's Healthcare of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Muna Qayed, MD, MS
Phone
404-785-1272
Email
mqayed@emory.edu
First Name & Middle Initial & Last Name & Degree
Muna Qayed
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Levine, MD, MS
Phone
212-241-1469
Email
john.levine@mssm.edu
First Name & Middle Initial & Last Name & Degree
John E Levine
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrew Harris, MD
Email
harrisa7@mskcc.org
First Name & Middle Initial & Last Name & Degree
Andrew Harris
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stephan Grupp, MD
Phone
215-590-5476
Email
grupp@email.chop.edu
First Name & Middle Initial & Last Name & Degree
Stephan Grupp
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37235
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carrie Kitko, MD
Phone
800-811-8480
Email
carrie.l.kitko@vumc.org
First Name & Middle Initial & Last Name & Degree
Carrie Kitko
Facility Name
The Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5S
Country
Canada
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Muhammad Ali, MD
Email
muhammad.ali@sickkids.ca
First Name & Middle Initial & Last Name & Degree
Muhammad Ali
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Patient did not consent to this.
Learn more about this trial
Pediatric GVHD Low Risk Steroid Taper Trial
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