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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | study day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Los Angeles | Los Angeles | California | 90027 | United States | ||
| Children's National Hospital |
Patient did not consent to this.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 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 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Participants | Participants | study day 28 |
|
1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alanine Aminotransferase Increased | Investigations | CTCAE 5.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and Lymphatic System Disorders | CTCAE 5.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. John E. Levine | Icahn School of Medicine at Mount Sinai | (212) 241-3429 | john.levine@mssm.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 3, 2025 | Apr 14, 2026 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Dec 30, 2023 | Apr 14, 2026 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D011241 | Prednisone |
| ID | Term |
|---|---|
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 |
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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
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|
| 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. | 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). | 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). | 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. | 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. | 12 months |
| Number of Participants Who Relapsed at 6 Months | Number of participants who relapsed of the underlying malignancy at 6 months. | 6 months |
| Relapse Rate at 12 Months | Relapse rate at 12 months Relapse, including date of relapse, of the underlying malignancy will be reported. | 12 months |
| Cumulative Incidence of Chronic GVHD | Cumulative incidence of chronic GVHD requiring systemic steroid treatment by one year from enrollment | 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. | 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. | study day 90 |
| Washington D.C. |
| District of Columbia |
| 20010 |
| United States |
| Children's Healthcare of Atlanta | Atlanta | Georgia | 30322 | United States |
| Boston Children's Hospital Dana Farber Cancer Institute | Boston | Massachusetts | 02115 | United States |
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37235 | United States |
| Texas Children's Hospital, Baylor College of Medicine | Houston | Texas | 77030 | United States |
| Medical College of Wisconsin / Children's Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
| The Hospital for Sick Children | Toronto | Ontario | M5S | Canada |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Diagnosis | Count of Participants | Participants |
|
| Donor Type | Human Leukocyte Antigen (HLA) | Count of Participants | Participants |
|
| Conditioning Regimen | Count of Participants | Participants |
|
| Antithymocyte globulin (ATG) used | Count of Participants | Participants |
|
| Graft-Versus-Host Disease (GVHD) Prophylaxis | calcineurin inhibitor (CNI); methotrexate (MTX); mycophenolate mofetil (MMF) | Count of Participants | Participants |
|
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | study day 28 |
|
|
|
| Secondary | 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. | Posted | Count of Participants | Participants | study day 90 |
|
|
|
| Secondary | 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). | Posted | Count of Participants | Participants | 6 months |
|
|
|
| Secondary | 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). | Not Posted | 12 months | Participants |
| Secondary | 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. | Posted | Count of Participants | Participants | 6 months |
|
|
|
| Secondary | 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. | Not Posted | 12 months | Participants |
| Secondary | Number of Participants Who Relapsed at 6 Months | Number of participants who relapsed of the underlying malignancy at 6 months. | Posted | Count of Participants | Participants | 6 months |
|
|
|
| Secondary | Relapse Rate at 12 Months | Relapse rate at 12 months Relapse, including date of relapse, of the underlying malignancy will be reported. | Not Posted | 12 months | Participants |
| Secondary | Cumulative Incidence of Chronic GVHD | Cumulative incidence of chronic GVHD requiring systemic steroid treatment by one year from enrollment | Not Posted | 12 months | Participants |
| Secondary | 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. | Posted | Mean | Standard Error | mg/kg | study day 28 |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Error | mg/kg | study day 90 |
|
|
|
| 5 |
| 50 |
| 20 |
| 50 |
| 8 |
| 50 |
| Hypotension | Vascular Disorders | CTCAE 5.0 | Systematic Assessment |
|
| Fever | General Disorders | CTCAE 5.0 | Systematic Assessment |
|
| Bacteremia | Infections and Infestations | CTCAE 5.0 | Systematic Assessment |
|
| Respiratory Failure | Respiratory, Thoracic and Mediastinal Disorders | CTCAE 5.0 | Systematic Assessment |
|
| Immune System Disorders - Other | Immune System Disorders | CTCAE 5.0 | Systematic Assessment |
|
| Lung Infection | Infections and Infestations | CTCAE 5.0 | Systematic Assessment |
|
| Hyponatremia | Metabolism and Nutrition Disorders | CTCAE 5.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal Disorders | CTCAE 5.0 | Systematic Assessment |
|
| Infections and Infestations - Other | Infections and Infestations | CTCAE 5.0 | Systematic Assessment |
|
| Metabolism and Nutrition Disorders - Other | Metabolism and Nutrition Disorders | CTCAE 5.0 | Systematic Assessment |
|
| Reversible Posterior Leukoencephalopathy Syndrome | Nervous System Disorders | CTCAE 5.0 | Systematic Assessment |
|
| Sepsis | Infections and Infestations | CTCAE 5.0 | Systematic Assessment |
|
| Respiratory, Thoracic and Mediastinal Disorders - Other | Respiratory, Thoracic and Mediastinal Disorders | CTCAE 5.0 | Systematic Assessment |
|
| Febrile Neutropenia | Blood and Lymphatic System Disorders | CTCAE 5.0 | Systematic Assessment |
|
| Enterocolitis Infectious | Infections and Infestations | CTCAE 5.0 | Systematic Assessment |
|
| Viremia | Infections and Infestations | CTCAE 5.0 | Systematic Assessment |
|
| Blood and Lymphatic System Disorders - Other | Blood and Lymphatic System Disorders | CTCAE 5.0 | Systematic Assessment |
|
| Vascular Disorders - Other | Vascular Disorders | CTCAE 5.0 | Systematic Assessment |
|
| Dehydration | Metabolism and Nutrition Disorders | CTCAE 5.0 | Systematic Assessment |
|
| Upper Respiratory Infection | Infections and Infestations | CTCAE 5.0 | Systematic Assessment |
|
| Skin and Subcutaneous Tissue Disorders - Other | Skin and Subcutaneous Tissue Disorders | CTCAE 5.0 | Systematic Assessment |
|
| Cardiac Disroders - Other | Cardiac Disorders | CTCAE 5.0 | Systematic Assessment |
|
| Alanine Aminotransferase Increased | Investigations | CTCAE 5.0 | Systematic Assessment |
|
| Platelet Count Decreased | Investigations | CTCAE 5.0 | Systematic Assessment |
|
| Lymphocyte Count Decreased | Investigations | CTCAE 5.0 | Systematic Assessment |
|
| White Blood Cell Decreased | Investigations | CTCAE 5.0 | Systematic Assessment |
|
| Aspartate Aminotransferase Increased | Investigations | CTCAE 5.0 | Systematic Assessment |
|
| Neutrophil Count Decreased | Investigations | CTCAE 5.0 | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | CTCAE 5.0 | Systematic Assessment |
|
| Infections and Infestations - Other | Infections and infestations | CTCAE 5.0 | Systematic Assessment |
|
| Blood Bilirubin Increased | Investigations | CTCAE 5.0 | Systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE 5.0 | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | CTCAE 5.0 | Systematic Assessment |
|
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| Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |