A Study to Evaluate Steroid-free Treatment for Standard-R... | NCT02806947

ID	Type	Description	Link
2U10HL069294-11	U.S. NIH Grant/Contract		View source
5U24CA076518	U.S. NIH Grant/Contract		View source

Status Module

Name	Class
National Heart, Lung, and Blood Institute (NHLBI)	NIH
National Cancer Institute (NCI)	NIH
Blood and Marrow Transplant Clinical Trials Network	NETWORK

Description Module

Label	Type	Description	Intervention Names
Sirolimus	Experimental	Sirolimus, a steroid-free therapy, will be administered after a diagnosis of standard-risk aGVHD is clinically established.	Drug: Sirolimus
Prednisone	Active Comparator	Prednisone, standard of care therapy for GVHD, will be administered after a diagnosis of standard-risk aGVHD is clinically established.	Drug: Prednisone

Name	Type	Description	Arm Group Labels	Other Names
Sirolimus	Drug	Sirolimus will be administered with a starting dose of 6 mg for patients older than 12 years, or 5 mg/m^2 for patients ≤ 12 years. Trough levels will be routinely measured and sirolimus will be kept at maintenance dosing for target therapeutic levels for minimum duration through Day 56 post-randomization.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Complete or Partial Response (CR/PR) to Acute GVHD Treatment	Scoring of CR/PR is in comparison to the participant's acute GVHD status at randomization. Complete response (CR) is defined as staging of 0 for in all target organs for GVHD - skin, GI tract, and liver. Partial response (PR) is defined as improvement in some target organ(s) without worsening in others. Death and initiation of systemic acute GVHD treatment beyond randomized treatment are considered failures for this endpoint. Organ staging is defined below: Skin stage: 0: No rash Rash <25% of body surface area (BSA) Rash on 25-50% of BSA Rash on >50% of BSA Generalized erythroderma with bullous formation Liver stage (based on bilirubin level): 0: <2 mg/dL 2-3 mg/dL 3.01-6 mg/dL 6.01-15.0 mg/dL >15 mg/dL GI stage: 0: No diarrhea or diarrhea <500 mL/day Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD Diarrhea 1000-1499 mL/day Diarrhea >1500 mL/day Severe abdominal pain with or without ileus	Days 28 and 56 Post-randomization

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Complete or Partial Response (CR/PR) and Steroid Dose Less Than 0.25 mg/kg Per Day	The proportion of patients with CR/PR and on a prednisone-equivalent steroid dose of 0.25 mg/kg/day or less is evaluated. CR/PR scoring is in comparison to acute GVHD status at randomization. CR is defined as staging of 0 in all target organs. PR is defined as improvement in some organ(s) without worsening in others. Death and initiation of steroid-free, systemic acute GVHD treatment beyond randomized therapy are considered failures for this endpoint. Organ staging is defined as: Skin stage: 0: No rash Rash <25% of body surface area (BSA) Rash 25-50% of BSA Rash >50% of BSA Generalized erythroderma with bullous formation Liver stage (based on bilirubin level in mg/dL): 0: <2 2-3 3.01-6 6.01-15.0 >15 mg/dL GI stage: 0: No diarrhea or diarrhea <500 mL/day Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD Diarrhea 1000-1499 mL/day Diarrhea >1500 mL/day Severe abdominal pain with or without ileus

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients with standard-risk acute GVHD, according to refined Minnesota Criteria. Refined Minnesota Criteria are available at https://redcap.ahc.umn.edu/surveys/?s=bNmFhseJIf.

Standard-risk acute GVHD according to the refined Minnesota Risk Criteria requires meeting one of the criteria below:
1. Single organ involvement (Stage 1-3 skin, Stage 1 upper GI, or Stage 1-2 lower GI)
2. Multiple organ involvement (Stage 1-3 skin plus stage 1 upper GI, Stage 1-3 skin plus stage 1 lower GI, Stage 1-3 skin plus stage 1 lower GI plus stage 1 upper GI, Stage 1-3 skin plus stage 1-4 liver, or Stage 1 lower GI plus stage 1 upper GI)
Acute Minnesota Standard Risk GVHD requiring systemic immune suppressive therapy.
Acute GVHD developing after allogeneic hematopoietic cell transplantation using either bone marrow, peripheral blood, or umbilical cord blood. Recipients of non-myeloablative, reduced intensity conditioning and myeloablative transplants are eligible. All allogeneic donor sources are permitted, including siblings, unrelated donors, human leukocyte antigen (HLA)-haploidentical related donors and umbilical cord blood.
Patients NOT receiving systemic immune suppressive therapy for treatment of active GVHD (topical skin and GI corticosteroids are allowed).
Ability to tolerate oral or enterically-administered medications.
Patients of all ages.
Absolute neutrophil count (ANC) greater than 500/µL.
Biopsy confirmation of GVHD is not required. Enrollment should not be delayed for biopsy or pathology results unless local institutional practice mandates biopsy confirmation to make a GVHD treatment decision.
Written informed consent and/or assent from patient, parent or guardian.
Collection of a 5 ml blood sample (red top for serum) from the patient for Ann Arbor Scoring and ready to be shipped immediately after randomization.

Exclusion Criteria:

Patients receiving sirolimus (for any indication including GVHD prophylaxis) within 14 days of screening for enrollment.
Relapsed, progressing or persistent malignancy requiring withdrawal of systemic immune suppression.
Patients with acute GVHD developing after a donor lymphocyte infusion.
Active or recent (within 7 days) episode of transplant associated microangiopathy.
Patients with uncontrolled infections will be excluded. Infections are considered controlled if appropriate therapy has been instituted and, at the time of enrollment, no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
Patients unlikely to be available for evaluation at the transplant center on Day 28 and 56 of therapy.
A clinical presentation resembling de novo chronic GVHD or overlap syndrome developing before or present at the time of enrollment.
Patients receiving corticosteroids for any indication within 7 days before the onset of acute GVHD, except the following: Stable replacement doses of corticosteroids for adrenal insufficiency are permitted (e.g. hydrocortisone total dose of 10-12 mg/m^2/day or prednisone 5-7.5mg daily or equivalent). Corticosteroids administered as premedication before transfusion of blood products or before intravenous medications to prevent infusion reactions are allowed.
Patients who are pregnant or breastfeeding.
Females of childbearing potential (FCBP) or a man who has sexual contact with a FCBP and is unwilling to use effective birth control for the duration of the study.
Patients on dialysis.
Patients on mechanical ventilation.
Patients with severe hepatic sinusoidal obstruction syndrome who in the judgment of the treating physician are not expected to have normalized bilirubin by Day 56 after enrollment.
Patients with a history of hypersensitivity to sirolimus or any component of the formulation.

Name	Affiliation	Role
Mary Horowitz, MD, MS	Center for International Blood and Marrow Transplant Research	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
City of Hope National Medical Center		Duarte	California	91010	United States
Children's Hospital Los Angeles

PubMed Identifier	Type	Citation	Retractions
16338616	Background	Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56. doi: 10.1016/j.bbmt.2005.09.004.
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Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Sirolimus	Sirolimus, a steroid-free therapy, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Sirolimus: Sirolimus will be administered with a starting dose of 6 mg for patients older than 12 years, or 5 mg/m^2 for patients ≤ 12 years. Trough levels will be routinely measured and sirolimus will be kept at maintenance dosing for target therapeutic levels for minimum duration through Day 56 post-randomization.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 7, 2017	Apr 23, 2019

Arm/Group Information

ID	Title	Description
BG000	Sirolimus	Sirolimus, a steroid-free therapy, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Sirolimus: Sirolimus will be administered with a starting dose of 6 mg for patients older than 12 years, or 5 mg/m^2 for patients ≤ 12 years. Trough levels will be routinely measured and sirolimus will be kept at maintenance dosing for target therapeutic levels for minimum duration through Day 56 post-randomization.
BG001	Prednisone	Prednisone, standard of care therapy for GVHD, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Prednisone: Prednisone will be administered at 2mg/kg/day x 3 days, and then tapered according to individual treating clinician judgment.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00058.0(7.8 to 74.7) BG00152.4(0.9 to 72.7) BG00254.6(0.9 to 74.7)

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00021 BG00131 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

American Indian / Alaska Native

Title	Measurements
	BG0000 BG0010 BG002

Ann Arbor Biomarker Risk Score

The Ann Arbor biomarker risk score is a scoring system for predicting risk of non-relapse mortality in patients with graft versus host disease. Risk is classified as 1, 2, or 3, where 1 denotes the lowest risk and 3 the highest risk.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
1	BG00038 BG001

Skin Abnormalities at Enrollment

Abnormalities in skin that are characteristics of graft versus host disease (GVHD) are tabulated.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
No active GVHD rash	BG00020 BG00119

Upper GI Abnormalities at Enrollment

Abnormalities in the upper GI tract that are characteristics of graft versus host disease (GVHD) are tabulated.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
No or Intermittent Nausea, Vomiting, or Anorexia	BG00032 BG00136

Lower GI Abnormalities at Enrollment

Diarrhea volume is tabulated, as diarrhea is characteristics of graft versus host disease (GVHD).

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
No Diarrhea	BG00053 BG00146

Liver Abnormalities at Enrollment

Abnormalities in the liver that are characteristics of graft versus host disease (GVHD) are tabulated.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Bilirubin <2.0mg/dL	BG00058 BG00163

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

Percentage of Participants With Complete or Partial Response (CR/PR) to Acute GVHD Treatment

Scoring of CR/PR is in comparison to the participant's acute GVHD status at randomization. Complete response (CR) is defined as staging of 0 for in all target organs for GVHD - skin, GI tract, and liver. Partial response (PR) is defined as improvement in some target organ(s) without worsening in others. Death and initiation of systemic acute GVHD treatment beyond randomized treatment are considered failures for this endpoint. Organ staging is defined below:

Skin stage:

0: No rash

Rash <25% of body surface area (BSA)
Rash on 25-50% of BSA
Rash on >50% of BSA
Generalized erythroderma with bullous formation

Liver stage (based on bilirubin level):

0: <2 mg/dL

2-3 mg/dL
3.01-6 mg/dL
6.01-15.0 mg/dL
>15 mg/dL

GI stage:

0: No diarrhea or diarrhea <500 mL/day

Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD
Diarrhea 1000-1499 mL/day
Diarrhea >1500 mL/day
Severe abdominal pain with or without ileus

CR/PR was evaluated in participants remaining on study until the assessment time point. At Day 28, one prednisone and four sirolimus arm participants were excluded from the analysis due to prior study withdrawal. At Day 56, one prednisone and five sirolimus arm participants were excluded from the analysis due to prior study withdrawal.

Posted

Count of Participants

Participants

Days 28 and 56 Post-randomization

ID	Title	Description
OG000	Sirolimus	Sirolimus, a steroid-free therapy, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Sirolimus: Sirolimus will be administered with a starting dose of 6 mg for patients older than 12 years, or 5 mg/m^2 for patients ≤ 12 years. Trough levels will be routinely measured and sirolimus will be kept at maintenance dosing for target therapeutic levels for minimum duration through Day 56 post-randomization.
OG001	Prednisone	Prednisone, standard of care therapy for GVHD, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Prednisone: Prednisone will be administered at 2mg/kg/day x 3 days, and then tapered according to individual treating clinician judgment.

Units	Counts
Participants	OG00058 OG00164

Title

Denominators

Categories

CR/PR at Day 28

- ParticipantsOG00054
- ParticipantsOG00163

Title	Measurements
Yes	OG00035

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The primary objective of this Phase II trial was to describe the proportion of patients with Day 28 CR/PR in each treatment arm and to estimate the risk difference of these rates using a point estimate and 90% confidence interval. These estimates are used to inform about the efficacy of sirolimus in contrast to prednisone for potential future research.					Risk Difference (RD)	-0.082	Standard Error of the Mean	0.086	2-Sided	90	-0.223	0.059			The risk difference estimate is the observed proportion of Day 28 CR/PR in the sirolimus arm minus the proportion in the prednisone arm. A Wald confidence interval for this difference is given.

Secondary

Percentage of Participants With Complete or Partial Response (CR/PR) and Steroid Dose Less Than 0.25 mg/kg Per Day

The proportion of patients with CR/PR and on a prednisone-equivalent steroid dose of 0.25 mg/kg/day or less is evaluated. CR/PR scoring is in comparison to acute GVHD status at randomization. CR is defined as staging of 0 in all target organs. PR is defined as improvement in some organ(s) without worsening in others. Death and initiation of steroid-free, systemic acute GVHD treatment beyond randomized therapy are considered failures for this endpoint. Organ staging is defined as:

Skin stage:

0: No rash

Rash <25% of body surface area (BSA)
Rash 25-50% of BSA
Rash >50% of BSA
Generalized erythroderma with bullous formation

Liver stage (based on bilirubin level in mg/dL):

0: <2

2-3
3.01-6
6.01-15.0
>15 mg/dL

GI stage:

0: No diarrhea or diarrhea <500 mL/day

Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD
Diarrhea 1000-1499 mL/day
Diarrhea >1500 mL/day
Severe abdominal pain with or without ileus

The endpoint was evaluated only in participants that remained on study until Day 28. One participant on the prednisone arm and four on the sirolimus arm were deemed unevaluable at Day 28 due to prior study withdrawal.

Posted

Count of Participants

Participants

Day 28 Post-randomization

ID	Title	Description
OG000	Sirolimus	Sirolimus, a steroid-free therapy, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Sirolimus: Sirolimus will be administered with a starting dose of 6 mg for patients older than 12 years, or 5 mg/m^2 for patients ≤ 12 years. Trough levels will be routinely measured and sirolimus will be kept at maintenance dosing for target therapeutic levels for minimum duration through Day 56 post-randomization.

Secondary

Acute GVHD Response

Acute GVHD response is classified as CR, PR, mixed response (MR), no response (NR), and progression and scored by comparison to acute GVHD status at randomization. MR is defined as improvement in some organ(s) with worsening in another, progression as worsening in some organ(s) without improvement in others, and NR as absence of any improvement or worsening. Death and initiation of systemic acute GVHD treatment beyond randomized treatment are classified as NR. Organ staging is defined as:

Skin stage:

0: No rash

Rash <25% of body surface area (BSA)
Rash 25-50% of BSA
Rash >50% of BSA
Generalized erythroderma with bullous formation

Liver stage (based on bilirubin level in mg/dL):

0: <2

2-3
3.01-6
6.01-15.0
>15

GI stage:

0: No diarrhea or diarrhea <500 mL/day

Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD
Diarrhea 1000-1499 mL/day
Diarrhea >1500 mL/day
Severe abdominal pain with or without ileus

Acute GVHD response was evaluated in participants remaining on study until the assessment day. At Day 28, one prednisone and four sirolimus arm participants were excluded from the analysis due to prior study withdrawal. At Day 56, one prednisone and five sirolimus arm participants were excluded from the analysis due to prior study withdrawal.

Posted

Count of Participants

Participants

Days 28 and 56 Post-randomization

ID	Title	Description
OG000	Sirolimus	Sirolimus, a steroid-free therapy, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Sirolimus: Sirolimus will be administered with a starting dose of 6 mg for patients older than 12 years, or 5 mg/m^2 for patients ≤ 12 years. Trough levels will be routinely measured and sirolimus will be kept at maintenance dosing for target therapeutic levels for minimum duration through Day 56 post-randomization.

Secondary

Percentage of Participants With Treatment Failure

Treatment failure is defined as either no response (NR) or progression and scored by comparison to acute GVHD status at randomization. Progression is defined as worsening in some target organ(s) without improvement in others and NR is defined as absence of any improvement or worsening in target organs. Death and initiation of systemic acute GVHD treatment beyond randomized treatment are classified as NR. Organ staging is defined as:

Skin stage:

0: No rash

Rash <25% of body surface area (BSA)
Rash 25-50% of BSA
Rash >50% of BSA
Generalized erythroderma with bullous formation

Liver stage (based on bilirubin level in mg/dL):

0: <2

2-3
3.01-6
6.01-15.0
>15

GI stage:

0: No diarrhea or diarrhea <500 mL/day

Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD
Diarrhea 1000-1499 mL/day
Diarrhea >1500 mL/day
Severe abdominal pain with or without ileus

Treatment failure was evaluated in participants remaining on study until the assessment day. At Day 28, one prednisone and four sirolimus arm participants were excluded from the analysis due to prior study withdrawal. At Day 56, one prednisone and five sirolimus arm participants were excluded from the analysis due to prior study withdrawal.

Posted

Count of Participants

Participants

Days 28 and 56 Post-randomization

ID	Title	Description
OG000	Sirolimus	Sirolimus, a steroid-free therapy, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Sirolimus: Sirolimus will be administered with a starting dose of 6 mg for patients older than 12 years, or 5 mg/m^2 for patients ≤ 12 years. Trough levels will be routinely measured and sirolimus will be kept at maintenance dosing for target therapeutic levels for minimum duration through Day 56 post-randomization.

Secondary

Percentage of Participants With Overall Survival

Overall survival is defined as survival of death from any cause.

Posted

Number

95% Confidence Interval

percentage of participants

6 and 12 Months Post-randomization

ID	Title	Description
OG000	Sirolimus	Sirolimus, a steroid-free therapy, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Sirolimus: Sirolimus will be administered with a starting dose of 6 mg for patients older than 12 years, or 5 mg/m^2 for patients ≤ 12 years. Trough levels will be routinely measured and sirolimus will be kept at maintenance dosing for target therapeutic levels for minimum duration through Day 56 post-randomization.
OG001	Prednisone	Prednisone, standard of care therapy for GVHD, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Prednisone: Prednisone will be administered at 2mg/kg/day x 3 days, and then tapered according to individual treating clinician judgment.

Units	Counts
Participants

Secondary

Percentage of Participants With Disease-free Survival

Disease-free survival is defined as freedom from death and relapse of the underlying malignancy.

Posted

Number

95% Confidence Interval

percentage of participants

6 and 12 Months Post-randomization

ID	Title	Description
OG000	Sirolimus	Sirolimus, a steroid-free therapy, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Sirolimus: Sirolimus will be administered with a starting dose of 6 mg for patients older than 12 years, or 5 mg/m^2 for patients ≤ 12 years. Trough levels will be routinely measured and sirolimus will be kept at maintenance dosing for target therapeutic levels for minimum duration through Day 56 post-randomization.
OG001	Prednisone	Prednisone, standard of care therapy for GVHD, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Prednisone: Prednisone will be administered at 2mg/kg/day x 3 days, and then tapered according to individual treating clinician judgment.

Units	Counts
Participants

Secondary

Proportion of Participants With Event-free Survival

Event-free survival is defined as freedom from acute GVHD progression, chronic GVHD, malignancy relapse, and death.

Posted

Number

95% Confidence Interval

percentage of participants

6 and 12 Months Post-randomization

ID	Title	Description
OG000	Sirolimus	Sirolimus, a steroid-free therapy, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Sirolimus: Sirolimus will be administered with a starting dose of 6 mg for patients older than 12 years, or 5 mg/m^2 for patients ≤ 12 years. Trough levels will be routinely measured and sirolimus will be kept at maintenance dosing for target therapeutic levels for minimum duration through Day 56 post-randomization.
OG001	Prednisone	Prednisone, standard of care therapy for GVHD, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Prednisone: Prednisone will be administered at 2mg/kg/day x 3 days, and then tapered according to individual treating clinician judgment.

Units	Counts
Participants

Secondary

Percentage of Participants With Non-relapse Mortality

Non-relapse mortality is defined as death due to any cause other than relapse of the underlying malignancy. The cumulative incidence of non-relapse mortality is described, with malignancy relapse treated as a competing risk.

Posted

Number

95% Confidence Interval

percentage of participants

6 and 12 Months Post-randomization

ID	Title	Description
OG000	Sirolimus	Sirolimus, a steroid-free therapy, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Sirolimus: Sirolimus will be administered with a starting dose of 6 mg for patients older than 12 years, or 5 mg/m^2 for patients ≤ 12 years. Trough levels will be routinely measured and sirolimus will be kept at maintenance dosing for target therapeutic levels for minimum duration through Day 56 post-randomization.
OG001	Prednisone	Prednisone, standard of care therapy for GVHD, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Prednisone: Prednisone will be administered at 2mg/kg/day x 3 days, and then tapered according to individual treating clinician judgment.

Units	Counts
Participants

Secondary

Percentage of Participants With Malignancy Relapse

The cumulative incidence of relapse of the primary malignancy is described, with death treated as a competing risk.

Posted

Number

95% Confidence Interval

percentage of participants

6 and 12 Months Post-randomization

ID	Title	Description
OG000	Sirolimus	Sirolimus, a steroid-free therapy, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Sirolimus: Sirolimus will be administered with a starting dose of 6 mg for patients older than 12 years, or 5 mg/m^2 for patients ≤ 12 years. Trough levels will be routinely measured and sirolimus will be kept at maintenance dosing for target therapeutic levels for minimum duration through Day 56 post-randomization.
OG001	Prednisone	Prednisone, standard of care therapy for GVHD, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Prednisone: Prednisone will be administered at 2mg/kg/day x 3 days, and then tapered according to individual treating clinician judgment.

Units	Counts
Participants

Secondary

Percentage of Participants With Chronic GVHD

Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification. The cumulative incidence of chronic GVHD is described, with death and malignancy relapse treated as competing risks.

Posted

Number

95% Confidence Interval

percentage of participants

6 and 12 Months Post-randomization

ID	Title	Description
OG000	Sirolimus	Sirolimus, a steroid-free therapy, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Sirolimus: Sirolimus will be administered with a starting dose of 6 mg for patients older than 12 years, or 5 mg/m^2 for patients ≤ 12 years. Trough levels will be routinely measured and sirolimus will be kept at maintenance dosing for target therapeutic levels for minimum duration through Day 56 post-randomization.
OG001	Prednisone	Prednisone, standard of care therapy for GVHD, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Prednisone: Prednisone will be administered at 2mg/kg/day x 3 days, and then tapered according to individual treating clinician judgment.

Secondary

Percentage of Participants With GVHD-free Survival

GVHD-free survival is defined as freedom from acute GVHD, chronic GVHD, and death. The proportion of participants alive and free of both acute and chronic GVHD are described at 6 and 12 months post-randomization.

GVHD-free survival was evaluated only in participants that remained on study until the assessment time point. One participant on the prednisone arm and five on the sirolimus arm were excluded from the analysis at 6 and 12 months due to prior study withdrawal.

Posted

Number

95% Confidence Interval

percentage of participants

6 and 12 Months Post-randomization

ID	Title	Description
OG000	Sirolimus	Sirolimus, a steroid-free therapy, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Sirolimus: Sirolimus will be administered with a starting dose of 6 mg for patients older than 12 years, or 5 mg/m^2 for patients ≤ 12 years. Trough levels will be routinely measured and sirolimus will be kept at maintenance dosing for target therapeutic levels for minimum duration through Day 56 post-randomization.
OG001	Prednisone	Prednisone, standard of care therapy for GVHD, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Prednisone: Prednisone will be administered at 2mg/kg/day x 3 days, and then tapered according to individual treating clinician judgment.

Secondary

Percentage of Participants With Serious Infections

The cumulative incidence of serious infections (Grade 2 or 3 per BMT CTN MOP) is described, with death treated as a competing risk.

Posted

Number

95% Confidence Interval

percentage of participants

6 and 12 Months Post-randomization

ID	Title	Description
OG000	Sirolimus	Sirolimus, a steroid-free therapy, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Sirolimus: Sirolimus will be administered with a starting dose of 6 mg for patients older than 12 years, or 5 mg/m^2 for patients ≤ 12 years. Trough levels will be routinely measured and sirolimus will be kept at maintenance dosing for target therapeutic levels for minimum duration through Day 56 post-randomization.
OG001	Prednisone	Prednisone, standard of care therapy for GVHD, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Prednisone: Prednisone will be administered at 2mg/kg/day x 3 days, and then tapered according to individual treating clinician judgment.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Sirolimus	Sirolimus, a steroid-free therapy, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Sirolimus: Sirolimus will be administered with a starting dose of 6 mg for patients older than 12 years, or 5 mg/m^2 for patients ≤ 12 years. Trough levels will be routinely measured and sirolimus will be kept at maintenance dosing for target therapeutic levels for minimum duration through Day 56 post-randomization.	12	58	8	58	0	58
EG001	Prednisone	Prednisone, standard of care therapy for GVHD, will be administered after a diagnosis of standard-risk aGVHD is clinically established. Prednisone: Prednisone will be administered at 2mg/kg/day x 3 days, and then tapered according to individual treating clinician judgment.	17	64	3	64	0	64

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected58 at risk EG0010 events0 affected64 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected58 at risk EG0010 events0 affected64 at risk
Appendicitis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected58 at risk EG0010 events0 affected64 at risk
Diverticulitis	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected58 at risk EG0010 events0 affected64 at risk
Pneumonia	Infections and infestations	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected58 at risk EG0010 events0 affected64 at risk
Failure to thrive	Metabolism and nutrition disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected58 at risk EG0010 events0 affected64 at risk
Delirium	Psychiatric disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected58 at risk EG0011 events1 affected64 at risk
Mental status changes	Psychiatric disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected58 at risk EG0010 events0 affected64 at risk
Cystitis noninfective	Renal and urinary disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected58 at risk EG0011 events1 affected64 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0000 events0 affected58 at risk EG0011 events1 affected64 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Non-systematic Assessment	EG0001 events1 affected58 at risk EG0010 events0 affected64 at risk

ID	Term
D018942	Macrolides
D007783	Lactones
D009930	Organic Chemicals
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds