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

• Sponsor: Medical College of Wisconsin (Other)
• Overall Status: Completed
• CT.gov ID: NCT01106833
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), National Cancer Institute (NCI) (NIH), Blood and Marrow Transplant Clinical Trials Network (Other), National Marrow Donor Program (Other)
• Enrollment: 151
• Locations: 31
• Arms: 2
• Actual Duration (Months): 98
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study is designed as a combined Phase II/III, randomized, open label, multicenter, prospective comparative study of sirolimus plus prednisone versus sirolimus/calcineurin-inhibitor plus prednisone for the treatment of chronic GVHD. Patients will be stratified by transplant center and will be randomized to an experimental arm of one of the two pre-specified experimental arms (sirolimus + prednisone or the comparator arm of sirolimus + calcineurin inhibitor + prednisone) in a 1:1 ratio.

Condition or Disease	Intervention/Treatment	Phase
Chronic GVHD	Drug: Sirolimus + calcineurin inhibitor + prednisone; Drug: Sirolimus + prednisone	Phase 2/Phase 3

Detailed Description

Background: Chronic GVHD is a medical condition that can become very serious. Chronic GVHD is a common development after allogeneic transplant that occurs when the donor cells attack and damage tissues. The primary purpose of this study is to compare treatment regimens that contain sirolimus without a calcineurin inhibitor to a comparator regimen of sirolimus with a calcineurin inhibitor and evaluate how well chronic GVHD responds to treatment. The combinations of medications in this study are:

• Sirolimus + calcineurin inhibitor + prednisone

• Sirolimus + prednisone

The goal is to select a treatment regimen for further comparison in the Phase III trial.

Design Narrative: The intent is to enroll subjects at the start of initial therapy for chronic GVHD, or before their chronic GVHD is refractory to glucocorticoid therapy, or is chronically dependent upon glucocorticoid therapy and multiple secondary systemic immunosuppressive agents. Patients will be stratified by transplant center and will be randomized to one of two arms.

Study Design

• Study Type: Interventional
• Actual Enrollment: 151 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II/III Randomized, Multicenter Trial Comparing Sirolimus Plus Prednisone and Sirolimus/Calcineurin Inhibitor Plus Prednisone for the Treatment of Chronic Graft-versus-Host Disease (BMT CTN Protocol #0801)
• Actual Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Feb 14, 2017
• Actual Study Completion Date: Jun 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: calcineurin inhibitor Sirolimus + calcineurin inhibitor + prednisone	Drug: 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.; Other Names: Rapamune Prograf Neorall Gengraf
Experimental: Sirolimus and prednisone Sirolimus + prednisone	Drug: 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.; Other Names: Rapamune

Outcome Measures

Primary Outcome Measures

1. Proportion of Participants With Treatment Success [6 months and 24 months post-randomization]

   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.

Secondary Outcome Measures

1. Percentage of Participants With Overall Survival [6 months and 24 months post-randomization]

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

2. Percentage of Participants With Progression-free Survival [6 months and 24 months post-randomization]

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

3. Percentage of Participants With Failure-free Survival [6 months and 24 months post-randomization]

   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.

4. Percentage of Participants With Relapse [6 months and 24 months post-randomization]

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

5. Percentage of Participants With Secondary Immunosuppressive Therapy Initiated [6 months and 24 months post-randomization]

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

6. Percentage of Participants With Discontinuation of Systemic Immunosuppressive Therapy at Two Years [2 years post-randomization]

   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.

7. Prednisone Dose [Baseline, 6 months, and 1 year post-randomization]

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

8. Change in Prednisone Dose From Baseline [6 months and 1 year post-randomization]

   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.

9. Serum Creatinine Level [Baseline, 6 months, and 1 year post-randomization]

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

10. Change in Serum Creatinine Level From Baseline [6 months and 1 year post-randomization]

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

11. Patient-reported Chronic GVHD Severity [Baseline, 6 months, 1 year, and 2 years post-randomization]

    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.

12. Provider-reported Chronic GVHD Severity [Baseline, 6 months, 1 year, and 2 years post-randomization]

    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.

13. NIH Consensus Criteria Chronic GVHD Severity [Baseline, 6 months, 1 year, and 2 years post-randomization]

    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.

14. SF-36 Physical Component Summary [Baseline, 2 months, 6 months, 1 year, and 2 years post-randomization]

    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.

15. SF-36 Mental Component Summary [Baseline, 2 months, 6 months, 1 year, and 2 years post-randomization]

    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.

16. FACT-BMT Score [Baseline, 2 months, 6 months, 1 year, and 2 years post-randomization]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	91010-3000
2	University of California San Diego Medical Center	La Jolla	California	United States	92093
3	Stanford Hospital and Clinics	Stanford	California	United States	94305
4	University of Florida College of Medicine (Shands)	Gainesville	Florida	United States	32610-0277
5	Emory University	Atlanta	Georgia	United States	30322
6	Blood & Marrow Transplant Program at Northside Hospital	Atlanta	Georgia	United States	30342
7	University of Chicago	Chicago	Illinois	United States	60637-1470
8	University of Kansas Hospital	Kansas City	Kansas	United States	66160
9	Johns Hopkins University	Baltimore	Maryland	United States	21231
10	University of Michigan Medical Center	Ann Arbor	Michigan	United States	48105-2967
11	University of Minnesota	Minneapolis	Minnesota	United States	55455
12	Washington University, Barnes Jewish Hospital	Saint Louis	Missouri	United States	63110
13	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-7680
14	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
15	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
16	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10174
17	Mayo Clinic	Rochester	New York	United States	55905
18	University of North Carolina Hospital at Chapel Hill	Chapel Hill	North Carolina	United States	27599-7305
19	Duke University Medical Center	Durham	North Carolina	United States	27705
20	Jewish Hospital BMT Program	Cincinnati	Ohio	United States	45236
21	University Hospitals of Cleveland/ Case Western	Cleveland	Ohio	United States	44106-5061
22	University of Oklahoma Medical Center	Oklahoma City	Oklahoma	United States	73104
23	Oregon Health & Science University (A) and (P)	Portland	Oregon	United States	97239-3098
24	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania	United States	19104
25	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania	United States	15224
26	Medical University of South Carolina	Charleston	South Carolina	United States	29425
27	University of Texas/MD Anderson CRC	Houston	Texas	United States	77030
28	Texas Transplant Institute	San Antonio	Texas	United States	78229
29	Virginia Commonwealth University/MCV Hospitals	Richmond	Virginia	United States	23298
30	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109-1024
31	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792-5156

Sponsors and Collaborators

• Medical College of Wisconsin
• National Heart, Lung, and Blood Institute (NHLBI)
• National Cancer Institute (NCI)
• Blood and Marrow Transplant Clinical Trials Network
• National Marrow Donor Program

Investigators

• Study Director: Mary Horowitz, MD, Center for International Blood and Marrow Transplant Research

Study Documents (Full-Text)

• Study Protocol - Jul 9, 2012
• Statistical Analysis Plan - May 20, 2016

More Information

Additional Information:

• BMT CTN Website
• National Marrow Donor Program

Publications

• 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.

• Responsible Party: Medical College of Wisconsin
• ClinicalTrials.gov Identifier: NCT01106833
• Other Study ID Numbers: BMTCTN0801; U01HL069294; BMT CTN 0801; U01HL06929406; 5U24CA076518
• First Posted: Apr 20, 2010
• Last Update Posted: Dec 5, 2018
• Last Verified: Nov 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Medical College of Wisconsin: Chronic Graft-versus-Host Disease (cGVHD)
• Additional relevant MeSH terms: Graft vs Host Disease; Sirolimus; Prednisone; Calcineurin Inhibitors

Study Results

Participant Flow

Arm/Group Title	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus and Prednisone
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	74	77
COMPLETED	74	77
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus and Prednisone	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	66	72	138
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.9 (14.2)	47.4 (16.1)	49.1 (15.2)
Age, Customized (Count of Participants)
Less Than 20	2 3%	5 6.9%	7 5.1%
20 - 40	12 18.2%	18 25%	30 21.7%
41 - 60	36 54.5%	30 41.7%	66 47.8%
Over 60	16 24.2%	19 26.4%	35 25.4%
Sex: Female, Male (Count of Participants)
Female	33 50%	24 33.3%	57 41.3%
Male	33 50%	48 66.7%	81 58.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	8 11.1%	8 5.8%
Not Hispanic or Latino	59 89.4%	63 87.5%	122 88.4%
Unknown or Not Reported	7 10.6%	1 1.4%	8 5.8%
Race/Ethnicity, Customized (Count of Participants)
White	57 86.4%	54 75%	111 80.4%
Non-white	9 13.6%	13 18.1%	22 15.9%
Unknown / Not Answered	0 0%	5 6.9%	5 3.6%
Primary Disease (Count of Participants)
Acute Leukemia	25 37.9%	47 65.3%	72 52.2%
Chronic Leukemia	8 12.1%	7 9.7%	15 10.9%
MDS / MPS	9 13.6%	12 16.7%	21 15.2%
Lymphoma	17 25.8%	5 6.9%	22 15.9%
Other	7 10.6%	1 1.4%	8 5.8%
Graft Type (Count of Participants)
Bone Marrow	5 7.6%	5 6.9%	10 7.2%
Peripheral Blood Stem Cells	60 90.9%	64 88.9%	124 89.9%
Single Cord Blood	1 1.5%	0 0%	1 0.7%
Double Cord Blood	0 0%	3 4.2%	3 2.2%
Donor Type (Count of Participants)
Related	38 57.6%	29 40.3%	67 48.6%
Unrelated	27 40.9%	40 55.6%	67 48.6%
Conditioning Regimen Intensity (Count of Participants)
Myeloablative	29 43.9%	47 65.3%	76 55.1%
Non-myeloablative or Reduced Intensity	37 56.1%	25 34.7%	62 44.9%
Donor Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.4 (15.2)	38.5 (12.9)	41.3 (14.0)
Donor Gender (Count of Participants)
Female	26 39.4%	35 48.6%	61 44.2%
Male	38 57.6%	37 51.4%	75 54.3%
Unknown	2 3%	0 0%	2 1.4%
Donor/Recipient Gender Matching (Count of Participants)
Female Donor, Female Recipient	10 15.2%	14 19.4%	24 17.4%
Female Donor, Male Recipient	16 24.2%	21 29.2%	37 26.8%
Male Donor, Female Recipient	21 31.8%	10 13.9%	31 22.5%
Male Donor, Male Recipient	17 25.8%	27 37.5%	44 31.9%
Unknown Donor Gender	2 3%	0 0%	2 1.4%

Outcome Measures

1. Primary Outcome

Title	Proportion of Participants With Treatment Success
Description	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.
Time Frame	6 months and 24 months post-randomization

Outcome Measure Data

Analysis Population Description

Twelve participants withdrew study consent between 6 and 24 months post-randomization, so are excluded from the analysis of treatment success at 24 months.

Arm/Group Title	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus and Prednisone
Arm/Group Description	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.	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.
Measure Participants	66	72
Yes	33 50%	35 48.6%
No	33 50%	37 51.4%
Yes	9 13.6%	10 13.9%
No	49 74.2%	58 80.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.63
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the proportion of participants with treatment success at 24 months is equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.44
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Fisher Exact
	Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus and Prednisone
Arm/Group Description	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.	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.
Measure Participants	66	72
6 Months	85.5 129.5%	91.7 127.4%
24 Months	74.0 112.1%	81.5 113.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the rate of overall survival during the first two years post-randomization is equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.205
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Log Rank
	Comments

3. Secondary Outcome

Title	Percentage of Participants With Progression-free Survival
Description	Progression-free Survival is defined as survival without malignancy relapse. Relapse and death are considered failures for this endpoint.
Time Frame	6 months and 24 months post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus and Prednisone
Arm/Group Description	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.	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.
Measure Participants	66	72
6 Months	84.0 127.3%	90.3 125.4%
24 Months	67.3 102%	78.6 109.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the rate of progression-free survival during the first two years post-randomization is equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.141
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Log Rank
	Comments

4. Secondary Outcome

Title	Percentage of Participants With Failure-free Survival
Description	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.
Time Frame	6 months and 24 months post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus and Prednisone
Arm/Group Description	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.	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.
Measure Participants	66	72
6 Months	74.7 113.2%	73.6 102.2%
24 Months	46.2 70%	48.6 67.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the rate of failure-free survival during the first two years post-randomization is equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.775
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Log Rank
	Comments

5. Secondary Outcome

Title	Percentage of Participants With Relapse
Description	Relapse is defined as recurrence of the primary malignancy. Death is considered a competing risk for this endpoint.
Time Frame	6 months and 24 months post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus and Prednisone
Arm/Group Description	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.	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.
Measure Participants	66	72
6 Months	4.8 7.3%	1.4 1.9%
24 Months	14.9 22.6%	10.1 14%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the rate of relapse during the first two years post-randomization is equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.396
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Gray's test
	Comments	Death without relapse was treated as a competing risk

6. Secondary Outcome

Title	Percentage of Participants With Secondary Immunosuppressive Therapy Initiated
Description	The percentage of participants initiating secondary immunosuppressive therapy for chronic GVHD is described. Death is considered a competing risk for this endpoint.
Time Frame	6 months and 24 months post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus and Prednisone
Arm/Group Description	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.	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.
Measure Participants	66	72
6 Months	12.9 19.5%	13.9 19.3%
24 months	29.4 44.5%	38.5 53.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the rate of initiation of secondary immunosuppressive therapy for chronic GVHD during the first two years post-randomization is equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.219
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Gray's test
	Comments	Death without initiation of secondary therapy is considered a competing risk for this endpoint

7. Secondary Outcome

Title	Percentage of Participants With Discontinuation of Systemic Immunosuppressive Therapy at Two Years
Description	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.
Time Frame	2 years post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus and Prednisone
Arm/Group Description	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.	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.
Measure Participants	66	72
Number (95% Confidence Interval) [percentage of participants]	20 30.3%	23.2 32.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the rate of discontinuation of systemic immunosuppressive therapy during the first two years post-randomization is equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.706
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Gray's test
	Comments	Death without discontinuation of systemic immunosuppressive therapy is considered a competing risk for this endpoint

8. Secondary Outcome

Title	Prednisone Dose
Description	Daily dose of prednisone is described by treatment arm at baseline, 6 months, and 1 year post-randomization.
Time Frame	Baseline, 6 months, and 1 year post-randomization

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus and Prednisone
Arm/Group Description	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.	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.
Measure Participants	66	72
Baseline	0.9	0.9
6 Months	0.2	0.2
1 Year	0.2	0.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the median prednisone dose at baseline is equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.127
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the median prednisone dose at 6 months post-randomization is equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.562
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the median prednisone dose at 1 year post-randomization is equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.129
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Kruskal-Wallis
	Comments

9. Secondary Outcome

Title	Change in Prednisone Dose From Baseline
Description	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.
Time Frame	6 months and 1 year post-randomization

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus and Prednisone
Arm/Group Description	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.	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.
Measure Participants	66	72
6 Months	-0.6	-0.6
1 Year	-0.6	-0.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the median change in prednisone dose from baseline to 6 months post-randomization is equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.586
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the median change in prednisone dose from baseline to 1 year post-randomization is equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.140
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Kruskal-Wallis
	Comments

10. Secondary Outcome

Title	Serum Creatinine Level
Description	Creatinine level is described by treatment arm at baseline, 6 months, and 1 year post-randomization.
Time Frame	Baseline, 6 months, and 1 year post-randomization

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus and Prednisone
Arm/Group Description	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.	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.
Measure Participants	66	72
Baseline	0.9	0.9
6 Months	1.0	1.0
1 Year	0.9	0.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the median serum creatinine level at baseline is equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.582
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the median serum creatinine level at 6 months post-randomization is equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.208
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the median serum creatinine level at 1 year post-randomization is equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.431
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Kruskal-Wallis
	Comments

11. Secondary Outcome

Title	Change in Serum Creatinine Level From Baseline
Description	Change in creatinine level from baseline, the time of randomization, is described by treatment arm at 6 months and 1 year post-randomization.
Time Frame	6 months and 1 year post-randomization

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus and Prednisone
Arm/Group Description	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.	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.
Measure Participants	66	72
6 Months	0.1	0.1
1 Year	0.0	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the median change in serum creatinine level from baseline to 6 months post-randomization is equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.147
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Kruskal-Wallis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the median change in serum creatinine level from baseline to 1 year post-randomization is equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.863
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Kruskal-Wallis
	Comments

12. Secondary Outcome

Title	Patient-reported Chronic GVHD Severity
Description	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.
Time Frame	Baseline, 6 months, 1 year, and 2 years post-randomization

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus and Prednisone
Arm/Group Description	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.	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.
Measure Participants	66	72
None	0 0%	0 0%
Mild	21 31.8%	20 27.8%
Moderate	23 34.8%	32 44.4%
Severe	10 15.2%	10 13.9%
Relapsed	0 0%	0 0%
Initiated Secondary Therapy	0 0%	0 0%
Dead	0 0%	0 0%
None	4 6.1%	6 8.3%
Mild	13 19.7%	25 34.7%
Moderate	15 22.7%	10 13.9%
Severe	2 3%	3 4.2%
Relapsed	3 4.5%	1 1.4%
Initiated Secondary Therapy	7 10.6%	14 19.4%
Dead	6 9.1%	4 5.6%
None	9 13.6%	2 2.8%
Mild	13 19.7%	23 31.9%
Moderate	4 6.1%	3 4.2%
Severe	0 0%	4 5.6%
Relapsed	5 7.6%	3 4.2%
Initiated Secondary Therapy	15 22.7%	21 29.2%
Dead	7 10.6%	4 5.6%
None	2 3%	6 8.3%
Mild	10 15.2%	13 18.1%
Moderate	2 3%	1 1.4%
Severe	0 0%	0 0%
Relapsed	8 12.1%	5 6.9%
Initiated Secondary Therapy	18 27.3%	28 38.9%
Dead	7 10.6%	4 5.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the proportions of patients in the patient-reported severity and vital status categories considered at baseline are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.620
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the proportions of patients in the patient-reported severity and vital status categories considered at 6 months post-randomization are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.258
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the proportions of patients in the patient-reported severity and vital status categories considered at 1 year post-randomization are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.036
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Fisher Exact
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the proportions of patients in the patient-reported severity and vital status categories considered at 2 years post-randomization are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.369
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Fisher Exact
	Comments

13. Secondary Outcome

Title	Provider-reported Chronic GVHD Severity
Description	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.
Time Frame	Baseline, 6 months, 1 year, and 2 years post-randomization

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus and Prednisone
Arm/Group Description	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.	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.
Measure Participants	66	72
None	1 1.5%	0 0%
Mild	13 19.7%	17 23.6%
Moderate	46 69.7%	48 66.7%
Severe	3 4.5%	7 9.7%
Relapsed	0 0%	0 0%
Initiated Secondary Therapy	0 0%	0 0%
Dead	0 0%	0 0%
None	6 9.1%	2 2.8%
Mild	27 40.9%	33 45.8%
Moderate	10 15.2%	13 18.1%
Severe	0 0%	0 0%
Relapsed	3 4.5%	1 1.4%
Initiated Secondary Therapy	7 10.6%	14 19.4%
Dead	6 9.1%	4 5.6%
None	8 12.1%	7 9.7%
Mild	15 22.7%	19 26.4%
Moderate	5 7.6%	9 12.5%
Severe	1 1.5%	1 1.4%
Relapsed	5 7.6%	3 4.2%
Initiated Secondary Therapy	15 22.7%	21 29.2%
Dead	7 10.6%	4 5.6%
None	7 10.6%	7 9.7%
Mild	10 15.2%	11 15.3%
Moderate	1 1.5%	4 5.6%
Severe	0 0%	0 0%
Relapsed	8 12.1%	5 6.9%
Initiated Secondary Therapy	18 27.3%	28 38.9%
Dead	7 10.6%	4 5.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the proportions of patients in the provider-reported severity and vital status categories considered at baseline are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.450
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the proportions of patients in the provider-reported severity and vital status categories considered at 6 months post-randomization are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.301
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the proportions of patients in the provider-reported severity and vital status categories considered at 1 year post-randomization are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.750
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Fisher Exact
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the proportions of patients in the provider-reported severity and vital status categories considered at 2 years post-randomization are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.444
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Fisher Exact
	Comments

14. Secondary Outcome

Title	NIH Consensus Criteria Chronic GVHD Severity
Description	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.
Time Frame	Baseline, 6 months, 1 year, and 2 years post-randomization

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus and Prednisone
Arm/Group Description	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.	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.
Measure Participants	66	72
None	0 0%	1 1.4%
Mild	1 1.5%	1 1.4%
Moderate	29 43.9%	23 31.9%
Severe	33 50%	46 63.9%
Relapsed	0 0%	0 0%
Initiated Secondary Therapy	0 0%	0 0%
Dead	0 0%	0 0%
None	3 4.5%	1 1.4%
Mild	3 4.5%	3 4.2%
Moderate	25 37.9%	27 37.5%
Severe	12 18.2%	17 23.6%
Relapsed	3 4.5%	1 1.4%
Initiated Secondary Therapy	7 10.6%	14 19.4%
Dead	6 9.1%	4 5.6%
None	2 3%	3 4.2%
Mild	2 3%	5 6.9%
Moderate	16 24.2%	16 22.2%
Severe	9 13.6%	10 13.9%
Relapsed	5 7.6%	3 4.2%
Initiated Secondary Therapy	15 22.7%	21 29.2%
Dead	7 10.6%	4 5.6%
None	9 13.6%	9 12.5%
Mild	6 9.1%	12 16.7%
Moderate	8 12.1%	8 11.1%
Severe	2 3%	2 2.8%
Relapsed	8 12.1%	5 6.9%
Initiated Secondary Therapy	18 27.3%	28 38.9%
Dead	7 10.6%	4 5.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the proportions of patients in the NIH Consensus Criteria severity and vital status categories considered at baseline are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.238
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the proportions of patients in the NIH Consensus Criteria severity and vital status categories considered at 6 months post-randomization are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.546
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the proportions of patients in the NIH Consensus Criteria severity and vital status categories considered at 1 year post-randomization are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.756
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Fisher Exact
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the proportions of patients in the NIH Consensus Criteria severity and vital status categories considered at 2 years post-randomization are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.554
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	Fisher Exact
	Comments

15. Secondary Outcome

Title	SF-36 Physical Component Summary
Description	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.
Time Frame	Baseline, 2 months, 6 months, 1 year, and 2 years post-randomization

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus and Prednisone
Arm/Group Description	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.	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.
Measure Participants	66	72
Baseline	38 (1.3)	38 (1.2)
2 Months	39 (1.6)	42 (1.6)
6 Months	38 (2.1)	43 (1.5)
1 Year	40 (1.8)	43 (1.7)
2 Years	44 (2.4)	43 (2.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the mean PCS scores at baseline are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.685
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	t-test, 2 sided
	Comments	Independent samples t-test

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the mean PCS scores at 2 months are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.105
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	t-test, 2 sided
	Comments	Independent samples t-test

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the mean PCS scores at 6 months are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.039
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	t-test, 2 sided
	Comments	Independent samples t-test

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the mean PCS scores at 1 year are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.278
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	t-test, 2 sided
	Comments	Independent samples t-test

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the mean PCS scores at 2 years are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.804
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	t-test, 2 sided
	Comments	Independent samples t-test

16. Secondary Outcome

Title	SF-36 Mental Component Summary
Description	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.
Time Frame	Baseline, 2 months, 6 months, 1 year, and 2 years post-randomization

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus and Prednisone
Arm/Group Description	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.	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.
Measure Participants	66	72
Baseline	47 (1.3)	48 (1.4)
2 Months	49 (1.4)	50 (1.5)
6 Months	50 (1.5)	48 (1.6)
1 Year	50 (1.7)	46 (2.1)
2 Years	52 (1.7)	50 (1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the mean MCS scores at baseline are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.631
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	t-test, 2 sided
	Comments	Independent samples t-test

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the mean MCS scores at 2 months are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.759
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	t-test, 2 sided
	Comments	Independent samples t-test

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the mean MCS scores at 6 months are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.391
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	t-test, 2 sided
	Comments	Independent samples t-test

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the mean MCS scores at 1 year are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.222
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	t-test, 2 sided
	Comments	Independent samples t-test

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the mean MCS scores at 2 years are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.527
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	t-test, 2 sided
	Comments	Independent samples t-test

17. Secondary Outcome

Title	FACT-BMT Score
Description	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.
Time Frame	Baseline, 2 months, 6 months, 1 year, and 2 years post-randomization

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Sirolimus, Calcineurin Inhibitor, and Prednisone	Sirolimus and Prednisone
Arm/Group Description	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.	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.
Measure Participants	66	72
Baseline	103 (2.6)	104 (2.5)
2 Months	105 (2.8)	110 (2.4)
6 Months	109 (3.2)	109 (3.4)
1 Year	114 (2.6)	110 (3.6)
2 Years	119 (3.8)	113 (3.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the mean FACT-BMT scores at baseline are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.763
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	t-test, 2 sided
	Comments	Independent samples t-test

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the mean FACT-BMT scores at 2 months are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.133
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	t-test, 2 sided
	Comments	Independent samples t-test

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the mean FACT-BMT scores at 6 months are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.953
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	t-test, 2 sided
	Comments	Independent samples t-test

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the mean FACT-BMT scores at 1 year are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.398
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	t-test, 2 sided
	Comments	Independent samples t-test

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Sirolimus, Calcineurin Inhibitor, and Prednisone, Sirolimus and Prednisone
	Comments	The null hypothesis is that the mean FACT-BMT scores at 2 years are equal for those receiving either Sirolimus, Calcineurin Inhibitor, and Prednisone or Sirolimus and Prednisone for treatment of chronic GVHD.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.309
	Comments	Two-sided testing was performed using a significance level of 0.05
	Method	t-test, 2 sided
	Comments	Independent samples t-test

Adverse Events

Time Frame	Three years post-randomization
Arm/Group Title	Sirolimus, Calcineurin Inhibitor, and Prednisone		Sirolimus and Prednisone
Arm/Group Description	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.		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.
All Cause Mortality
	Sirolimus, Calcineurin Inhibitor, and Prednisone		Sirolimus and Prednisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/66 (24.2%)		13/72 (18.1%)
Serious Adverse Events
	Sirolimus, Calcineurin Inhibitor, and Prednisone		Sirolimus and Prednisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/66 (19.7%)		12/72 (16.7%)
Blood and lymphatic system disorders
Thrombotic thrombocytopenic purpura	1/66 (1.5%)	1	0/72 (0%)	0
Cardiac disorders
Bradycardia	0/66 (0%)	0	1/72 (1.4%)	1
Cardiac fibrillation	1/66 (1.5%)	1	0/72 (0%)	0
Coronary artery disease	0/66 (0%)	0	1/72 (1.4%)	1
Myocardial infarction	1/66 (1.5%)	1	1/72 (1.4%)	1
Gastrointestinal disorders
Gastric ulcer	1/66 (1.5%)	1	0/72 (0%)	0
Hepatobiliary disorders
Cholecystitis	1/66 (1.5%)	1	0/72 (0%)	0
Infections and infestations
Sepsis	2/66 (3%)	3	1/72 (1.4%)	1
Injury, poisoning and procedural complications
Hip fracture	1/66 (1.5%)	1	0/72 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma	1/66 (1.5%)	1	0/72 (0%)	0
Nervous system disorders
Cerebrovascular accident	0/66 (0%)	0	1/72 (1.4%)	1
Loss of consciousness	0/66 (0%)	0	1/72 (1.4%)	1
Neuropathy peripheral	0/66 (0%)	0	1/72 (1.4%)	1
Syncope	1/66 (1.5%)	1	2/72 (2.8%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/66 (1.5%)	1	0/72 (0%)	0
Pleural effusion	0/66 (0%)	0	1/72 (1.4%)	1
Pulmonary embolism	1/66 (1.5%)	1	0/72 (0%)	0
Surgical and medical procedures
Splenectomy	0/66 (0%)	0	1/72 (1.4%)	1
Vascular disorders
Deep vein thrombosis	1/66 (1.5%)	1	1/72 (1.4%)	1
Other (Not Including Serious) Adverse Events
	Sirolimus, Calcineurin Inhibitor, and Prednisone		Sirolimus and Prednisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/66 (0%)		0/72 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.