Chronic Graft-versus-Host Disease Treatment (BMT CTN 0801) | NCT01106833

NCT01106833

Secondary IDs

ID	Type	Description	Link
U01HL069294	U.S. NIH Grant/Contract		View source
BMT CTN 0801	Other Identifier	Blood and Marrow Transplant Clinical Trials Network
U01HL06929406	Other Grant/Funding Number	National Cancer Institute (NCI)
5U24CA076518	U.S. NIH Grant/Contract		View source

Status Module

Sponsor/Collaborators Module

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

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
calcineurin inhibitor	Active Comparator	Sirolimus + calcineurin inhibitor + prednisone	Drug: Sirolimus + calcineurin inhibitor + prednisone
Sirolimus and prednisone	Experimental	Sirolimus + prednisone	Drug: Sirolimus + prednisone

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Sirolimus + calcineurin inhibitor + prednisone	Drug	The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Proportion of Participants With Treatment Success	Treatment success was evaluated at 6 months in Phase II and is defined as a complete or partial response without secondary systemic immunosuppressive therapy and no recurrent malignancy or death. In Phase III, treatment success was evaluated at 24 months and is defined as a complete response without secondary systemic immunosuppressive therapy and no recurrent malignancy or death.	6 months and 24 months post-randomization

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Overall Survival	Overall survival is defined as survival of death from any cause.	6 months and 24 months post-randomization
Percentage of Participants With Progression-free Survival

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Suitable candidates are patients with classic chronic GVHD or overlap syndrome (classic chronic plus acute GVHD)that is: a)Previously untreated (newly diagnosed) as defined by having received < 14 days of prednisone (or equivalent) before enrollment/randomization to study therapy; b)Previously treated but inadequately responding after ≤ 16 weeks of initial therapy with prednisone and/or calcineurin inhibitor (CNI) ± additional non-sirolimus agent (started at the time of chronic GVHD diagnosis).
Patient or guardian willing and able to provide informed consent.
Stated willingness to use contraception in women of childbearing potential.
Stated willingness of patient to comply with study procedures and reporting requirements.

Exclusion Criteria:

Patients with late persistent acute GVHD or recurrent acute GVHD only.
Inability to begin prednisone therapy at a dose of greater than 0.5 mg/kg/day.
Receiving sirolimus for treatment of chronic GVHD (sirolimus for prophylaxis or treatment of acute GVHD is acceptable).
Already receiving sirolimus (for prophylaxis or treatment of acute GVHD) with prednisone at ≥ 0.25 mg/kg/day (or equivalent) ± additional agents.
Receiving therapy for chronic GVHD for more than 16 weeks.
Invasive fungal or viral infection not responding to appropriate antifungal or antiviral therapies.
Inadequate renal function defined as measured creatinine clearance less than 50 mL/min/1.73 m^2 based on the Cockcroft-Gault formula (adults) or Schwartz formula (age less than or equal to 12 years). Adults: estimated creatinine clearance rate (eCCr) (mL/min/) = (140 - age) x mass (kg) x (0.85 if female)/72 x serum creatinine (mg/dL; Creatinine clearance (mL/min/1.73m^2) = eCCr x 1.73/Body Surface Area (BSA) (m^2); Children: eCCr (mL/min/1.73 m^2) = k x height (cm) / serum creatinine (mg/dL) k = 0.33 (pre-term), 0.45 (full term to 1 year old), 0.55 (age 1-12 years).
Inability to tolerate oral medications.
Absolute neutrophil count less than 1500 per microliter.
Requirement for platelet transfusions.
Pregnancy (positive serum β-HCG) or breastfeeding.
Receiving any treatment for persistent, progressive or recurrent malignancy.
Progressive or recurrent malignancy defined other than by quantitative molecular assays.
Known hypersensitivity to sirolimus.

Contacts/Locations Module

Name	Affiliation	Role
Mary Horowitz, MD	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	91010-3000	United States
University of California San Diego Medical Center

References Module

Citations

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.
29954931

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus + calcineurin inhibitor + prednisone Sirolimus + calcineurin inhibitor + prednisone: The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document 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 9, 2012	Jul 3, 2018

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Progression-free Survival is defined as survival without malignancy relapse. Relapse and death are considered failures for this endpoint.

Analysis population includes only participants deemed to be eligible per Endpoint Review Committee adjudication. Thirteen enrolled participants were classified as ineligible (8 on the Sirolimus+Calcineurin Inhibitor+Prednisone arm and 5 on the Sirolimus+Prednisone arm) and are excluded from the analysis.

Arm/Group Information

ID	Title	Description
BG000	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus + calcineurin inhibitor + prednisone Sirolimus + calcineurin inhibitor + prednisone: The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.
BG001	Sirolimus and Prednisone	Sirolimus + prednisone Sirolimus + prednisone: The target serum level for sirolimus is 3-12 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.
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

Mean

Standard Deviation

years

Title

Denominators

Categories

Phase II: 6 Months

- ParticipantsOG00066
- ParticipantsOG00172

Title	Measurements
Yes	OG00033

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 null hypothesis is that the proportion of participants with treatment success at 6 months is equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.	Fisher Exact		0.63	Two-sided testing was performed using a significance level of 0.05													Superiority

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 months and 24 months post-randomization

ID	Title	Description
OG000	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus + calcineurin inhibitor + prednisone Sirolimus + calcineurin inhibitor + prednisone: The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.
OG001	Sirolimus and Prednisone	Sirolimus + prednisone Sirolimus + prednisone: The target serum level for sirolimus is 3-12 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

Units	Counts
Participants

Secondary

Percentage of Participants With Progression-free Survival

Progression-free Survival is defined as survival without malignancy relapse. Relapse and death are considered failures for this endpoint.

Posted

Number

95% Confidence Interval

percentage of participants

6 months and 24 months post-randomization

ID	Title	Description
OG000	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus + calcineurin inhibitor + prednisone Sirolimus + calcineurin inhibitor + prednisone: The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.
OG001	Sirolimus and Prednisone	Sirolimus + prednisone Sirolimus + prednisone: The target serum level for sirolimus is 3-12 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

Units

Secondary

Percentage of Participants With Failure-free Survival

Failure-free Survival is defined as survival without malignancy progression or initiation of secondary therapy for chronic GVHD. Progression, initiation of secondary therapy for chronic GVHD, and death are considered failures for this endpoint.

Posted

Number

95% Confidence Interval

percentage of participants

6 months and 24 months post-randomization

ID	Title	Description
OG000	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus + calcineurin inhibitor + prednisone Sirolimus + calcineurin inhibitor + prednisone: The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.
OG001	Sirolimus and Prednisone	Sirolimus + prednisone Sirolimus + prednisone: The target serum level for sirolimus is 3-12 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

Secondary

Percentage of Participants With Relapse

Relapse is defined as recurrence of the primary malignancy. Death is considered a competing risk for this endpoint.

Posted

Number

95% Confidence Interval

percentage of participants

6 months and 24 months post-randomization

ID	Title	Description
OG000	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus + calcineurin inhibitor + prednisone Sirolimus + calcineurin inhibitor + prednisone: The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.
OG001	Sirolimus and Prednisone	Sirolimus + prednisone Sirolimus + prednisone: The target serum level for sirolimus is 3-12 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

Units	Counts

Secondary

Percentage of Participants With Secondary Immunosuppressive Therapy Initiated

The percentage of participants initiating secondary immunosuppressive therapy for chronic GVHD is described. Death is considered a competing risk for this endpoint.

Posted

Number

95% Confidence Interval

percentage of participants

6 months and 24 months post-randomization

ID	Title	Description
OG000	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus + calcineurin inhibitor + prednisone Sirolimus + calcineurin inhibitor + prednisone: The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.
OG001	Sirolimus and Prednisone	Sirolimus + prednisone Sirolimus + prednisone: The target serum level for sirolimus is 3-12 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

Secondary

Percentage of Participants With Discontinuation of Systemic Immunosuppressive Therapy at Two Years

The percentage of participants discontinuing all systemic immunosuppressive therapy by two years post-randomization is described. Death is considered a competing risk for this endpoint.

Posted

Number

95% Confidence Interval

percentage of participants

2 years post-randomization

ID	Title	Description
OG000	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus + calcineurin inhibitor + prednisone Sirolimus + calcineurin inhibitor + prednisone: The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.
OG001	Sirolimus and Prednisone	Sirolimus + prednisone Sirolimus + prednisone: The target serum level for sirolimus is 3-12 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

Secondary

Prednisone Dose

Daily dose of prednisone is described by treatment arm at baseline, 6 months, and 1 year post-randomization.

Outcomes are analyzed in participants that were alive and completed assessments.

Posted

Median

Full Range

mg/kg/day

Baseline, 6 months, and 1 year post-randomization

ID	Title	Description
OG000	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus + calcineurin inhibitor + prednisone Sirolimus + calcineurin inhibitor + prednisone: The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.
OG001	Sirolimus and Prednisone	Sirolimus + prednisone Sirolimus + prednisone: The target serum level for sirolimus is 3-12 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

Secondary

Change in Prednisone Dose From Baseline

Change in the daily dose of prednisone from baseline, the time of randomization, is described by treatment arm at 6 months and 1 year post-randomization.

Outcomes are analyzed in participants that were alive and completed assessments.

Posted

Median

Full Range

mg/kg/day

6 months and 1 year post-randomization

ID	Title	Description
OG000	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus + calcineurin inhibitor + prednisone Sirolimus + calcineurin inhibitor + prednisone: The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.
OG001	Sirolimus and Prednisone	Sirolimus + prednisone Sirolimus + prednisone: The target serum level for sirolimus is 3-12 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

Secondary

Serum Creatinine Level

Creatinine level is described by treatment arm at baseline, 6 months, and 1 year post-randomization.

Outcomes are analyzed in participants that were alive and completed assessments.

Posted

Median

Full Range

mg/dL

Baseline, 6 months, and 1 year post-randomization

ID	Title	Description
OG000	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus + calcineurin inhibitor + prednisone Sirolimus + calcineurin inhibitor + prednisone: The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.
OG001	Sirolimus and Prednisone	Sirolimus + prednisone Sirolimus + prednisone: The target serum level for sirolimus is 3-12 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

Secondary

Change in Serum Creatinine Level From Baseline

Change in creatinine level from baseline, the time of randomization, is described by treatment arm at 6 months and 1 year post-randomization.

Outcomes are analyzed in participants that were alive and completed assessments.

Posted

Median

Full Range

mg/dL

6 months and 1 year post-randomization

ID	Title	Description
OG000	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus + calcineurin inhibitor + prednisone Sirolimus + calcineurin inhibitor + prednisone: The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.
OG001	Sirolimus and Prednisone	Sirolimus + prednisone Sirolimus + prednisone: The target serum level for sirolimus is 3-12 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

Secondary

Patient-reported Chronic GVHD Severity

Each patient's perception of the severity of the chronic GVHD was collected at baseline and at 6 months, 1 year, and 2 years post-randomization. Severity is categorized as none, mild, moderate, and severe.

Outcomes are analyzed in participants that were alive and completed assessments.

Posted

Count of Participants

Participants

Baseline, 6 months, 1 year, and 2 years post-randomization

ID	Title	Description
OG000	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus + calcineurin inhibitor + prednisone Sirolimus + calcineurin inhibitor + prednisone: The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.
OG001	Sirolimus and Prednisone	Sirolimus + prednisone Sirolimus + prednisone: The target serum level for sirolimus is 3-12 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

Secondary

Provider-reported Chronic GVHD Severity

Each patient's care provider's perception of the severity of the chronic GVHD was collected at baseline and at 6 months, 1 year, and 2 years post-randomization. Severity is categorized as none, mild, moderate, and severe.

Outcomes are analyzed in participants that were alive and whose providers completed assessments.

Posted

Count of Participants

Participants

Baseline, 6 months, 1 year, and 2 years post-randomization

ID	Title	Description
OG000	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus + calcineurin inhibitor + prednisone Sirolimus + calcineurin inhibitor + prednisone: The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.
OG001	Sirolimus and Prednisone	Sirolimus + prednisone Sirolimus + prednisone: The target serum level for sirolimus is 3-12 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

Secondary

NIH Consensus Criteria Chronic GVHD Severity

Chronic GVHD severity was determined at baseline and at 6 months, 1 year, and 2 years post-randomization per the 2005 NIH Consensus Criteria (Filipovich et al. 2005). Severity is categorized as none, mild, moderate, and severe.

Outcomes are analyzed in participants that were alive and whose clinical assessments were completed.

Posted

Count of Participants

Participants

Baseline, 6 months, 1 year, and 2 years post-randomization

ID	Title	Description
OG000	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus + calcineurin inhibitor + prednisone Sirolimus + calcineurin inhibitor + prednisone: The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.
OG001	Sirolimus and Prednisone	Sirolimus + prednisone Sirolimus + prednisone: The target serum level for sirolimus is 3-12 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

Secondary

SF-36 Physical Component Summary

The Medical Outcome Study SF-36 Physical Component Summary (PCS) is a subscale of the SF-36 intended to measure physical well-being. It is scored on a scale of 0-100, with higher scores indicating higher levels of well-being.

Outcomes are analyzed in participants that were alive and completed assessments.

Posted

Mean

Standard Error

score on a scale

Baseline, 2 months, 6 months, 1 year, and 2 years post-randomization

ID	Title	Description
OG000	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus + calcineurin inhibitor + prednisone Sirolimus + calcineurin inhibitor + prednisone: The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.
OG001	Sirolimus and Prednisone	Sirolimus + prednisone Sirolimus + prednisone: The target serum level for sirolimus is 3-12 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

Secondary

SF-36 Mental Component Summary

The Medical Outcome Study SF-36 Mental Component Summary (MCS) is a subscale of the SF-36 intended to measure mental well-being. It is scored on a scale of 0-100, with higher scores indicating higher levels of well-being.

Outcomes are analyzed in participants that were alive and completed assessments.

Posted

Mean

Standard Error

score on a scale

Baseline, 2 months, 6 months, 1 year, and 2 years post-randomization

ID	Title	Description
OG000	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus + calcineurin inhibitor + prednisone Sirolimus + calcineurin inhibitor + prednisone: The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.
OG001	Sirolimus and Prednisone	Sirolimus + prednisone Sirolimus + prednisone: The target serum level for sirolimus is 3-12 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

Secondary

FACT-BMT Score

The Functional Assessment of Cancer Therapy-Bone Marrow Transplant scale (FACT-BMT) is a quality of life instrument that assesses the effects of bone marrow transplantation (BMT) on a patient's physical, social/family, emotional, and functional well-being while taking into consideration BMT-specific concerns. The assessment has 37 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-148, with higher scores indicating higher levels of overall well-being.

Outcomes are analyzed in participants that were alive and completed assessments.

Posted

Mean

Standard Error

score on a scale

Baseline, 2 months, 6 months, 1 year, and 2 years post-randomization

ID	Title	Description
OG000	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus + calcineurin inhibitor + prednisone Sirolimus + calcineurin inhibitor + prednisone: The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.
OG001	Sirolimus and Prednisone	Sirolimus + prednisone Sirolimus + prednisone: The target serum level for sirolimus is 3-12 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.

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, Calcineurin Inhibitor, and Prednisone	Sirolimus + calcineurin inhibitor + prednisone Sirolimus + calcineurin inhibitor + prednisone: The target serum level for sirolimus is 3-12 ng/mL. The target serum level for tacrolimus is 5-10 ng/mL. The target serum level for cyclosporine is 120-200 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.	16	66	13	66	0	66
EG001	Sirolimus and Prednisone	Sirolimus + prednisone Sirolimus + prednisone: The target serum level for sirolimus is 3-12 ng/mL. Prednisone is administered initially as a single early morning dose of 1 mg/kg/day (or equivalent). If prednisone at a dose of 1 mg/kg/day (or equivalent) is contraindicated, patients may begin prednisone between 0.5-1 mg/kg/day.	13	72	12	72	0	72

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Thrombotic thrombocytopenic purpura	Blood and lymphatic system disorders	Non-systematic Assessment	EG0001 events1 affected66 at risk EG0010 events0 affected72 at risk
Bradycardia	Cardiac disorders	Non-systematic Assessment	EG0000 events0 affected66 at risk EG0011 events1 affected72 at risk
Cardiac fibrillation	Cardiac disorders	Non-systematic Assessment	EG0001 events1 affected66 at risk EG0010 events0 affected72 at risk
Coronary artery disease	Cardiac disorders	Non-systematic Assessment	EG0000 events0 affected66 at risk EG0011 events1 affected72 at risk
Myocardial infarction	Cardiac disorders	Non-systematic Assessment	EG0001 events1 affected66 at risk EG0011 events1 affected72 at risk
Gastric ulcer	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected66 at risk EG0010 events0 affected72 at risk
Cholecystitis	Hepatobiliary disorders	Non-systematic Assessment	EG0001 events1 affected66 at risk EG0010 events0 affected72 at risk
Sepsis	Infections and infestations	Non-systematic Assessment	EG0003 events2 affected66 at risk EG0011 events1 affected72 at risk
Hip fracture	Injury, poisoning and procedural complications	Non-systematic Assessment	EG0001 events1 affected66 at risk EG0010 events0 affected72 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	Non-systematic Assessment	EG0001 events1 affected66 at risk EG0010 events0 affected72 at risk
Cerebrovascular accident	Nervous system disorders	Non-systematic Assessment	EG0000 events0 affected66 at risk EG0011 events1 affected72 at risk
Loss of consciousness	Nervous system disorders	Non-systematic Assessment	EG0000 events0 affected66 at risk EG0011 events1 affected72 at risk
Neuropathy peripheral	Nervous system disorders	Non-systematic Assessment	EG0000 events0 affected66 at risk EG0011 events1 affected72 at risk
Syncope	Nervous system disorders	Non-systematic Assessment	EG0001 events1 affected66 at risk EG0012 events2 affected72 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected66 at risk EG0010 events0 affected72 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0000 events0 affected66 at risk EG0011 events1 affected72 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected66 at risk EG0010 events0 affected72 at risk
Splenectomy	Surgical and medical procedures	Non-systematic Assessment	EG0000 events0 affected66 at risk EG0011 events1 affected72 at risk
Deep vein thrombosis	Vascular disorders	Non-systematic Assessment	EG0001 events1 affected66 at risk EG0011 events1 affected72 at risk

ID	Term
D000092122	Bronchiolitis Obliterans Syndrome

Ancestor Terms

ID	Term
D000092124	Organizing Pneumonia
D001989	Bronchiolitis Obliterans
D001988	Bronchiolitis
D001991	Bronchitis
D001982	Bronchial Diseases
D012140	Respiratory Tract Diseases
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D006086	Graft vs Host Disease
D007154	Immune System Diseases

ID	Term
D020123	Sirolimus
D065095	Calcineurin Inhibitors
D011241	Prednisone
D016559	Tacrolimus
D003524	Cyclosporins

Ancestor Terms

ID	Term
D018942	Macrolides
D007783	Lactones
D009930	Organic Chemicals
D004791	Enzyme Inhibitors
D045504	Molecular Mechanisms of Pharmacological Action
D020228	Pharmacologic Actions
D020164	Chemical Actions and Uses
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D010456	Peptides, Cyclic
D047028	Macrocyclic Compounds
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins

Units	Counts
Participants	OG00066 OG00172

Units	Counts
Participants	OG00066 OG00172

Units	Counts
Participants	OG00066 OG00172

Units	Counts
Participants	OG00066 OG00172

Units	Counts
Participants	OG00066 OG00172