Chronic GVHD
Conditions
Keywords
Chronic Graft-versus-Host Disease (cGVHD)
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.
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.
Interventions
DRUGSirolimus + 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.
DRUGSirolimus + 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.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
National Cancer Institute (NCI)
Blood and Marrow Transplant Clinical Trials Network
National Marrow Donor Program
Medical College of Wisconsin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Percentage of Participants With Overall Survival | 6 months and 24 months post-randomization | Overall survival is defined as survival of death from any cause. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 66 |
| 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. | 72 |
| Total | 138 |
Baseline characteristics
| Characteristic | Sirolimus, Calcineurin Inhibitor, and Prednisone | Sirolimus and Prednisone | Total |
|---|---|---|---|
| Age, Continuous | 50.9 years STANDARD_DEVIATION 14.2 | 47.4 years STANDARD_DEVIATION 16.1 | 49.1 years STANDARD_DEVIATION 15.2 |
| Age, Customized 20 - 40 | 12 Participants | 18 Participants | 30 Participants |
| Age, Customized 41 - 60 | 36 Participants | 30 Participants | 66 Participants |
| Age, Customized Less Than 20 | 2 Participants | 5 Participants | 7 Participants |
| Age, Customized Over 60 | 16 Participants | 19 Participants | 35 Participants |
| Conditioning Regimen Intensity Myeloablative | 29 Participants | 47 Participants | 76 Participants |
| Conditioning Regimen Intensity Non-myeloablative or Reduced Intensity | 37 Participants | 25 Participants | 62 Participants |
| Donor Age | 44.4 years STANDARD_DEVIATION 15.2 | 38.5 years STANDARD_DEVIATION 12.9 | 41.3 years STANDARD_DEVIATION 14 |
| Donor Gender Female | 26 Participants | 35 Participants | 61 Participants |
| Donor Gender Male | 38 Participants | 37 Participants | 75 Participants |
| Donor Gender Unknown | 2 Participants | 0 Participants | 2 Participants |
| Donor/Recipient Gender Matching Female Donor, Female Recipient | 10 Participants | 14 Participants | 24 Participants |
| Donor/Recipient Gender Matching Female Donor, Male Recipient | 16 Participants | 21 Participants | 37 Participants |
| Donor/Recipient Gender Matching Male Donor, Female Recipient | 21 Participants | 10 Participants | 31 Participants |
| Donor/Recipient Gender Matching Male Donor, Male Recipient | 17 Participants | 27 Participants | 44 Participants |
| Donor/Recipient Gender Matching Unknown Donor Gender | 2 Participants | 0 Participants | 2 Participants |
| Donor Type Related | 38 Participants | 29 Participants | 67 Participants |
| Donor Type Unrelated | 27 Participants | 40 Participants | 67 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 8 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 59 Participants | 63 Participants | 122 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 1 Participants | 8 Participants |
| Graft Type Bone Marrow | 5 Participants | 5 Participants | 10 Participants |
| Graft Type Double Cord Blood | 0 Participants | 3 Participants | 3 Participants |
| Graft Type Peripheral Blood Stem Cells | 60 Participants | 64 Participants | 124 Participants |
| Graft Type Single Cord Blood | 1 Participants | 0 Participants | 1 Participants |
| Primary Disease Acute Leukemia | 25 Participants | 47 Participants | 72 Participants |
| Primary Disease Chronic Leukemia | 8 Participants | 7 Participants | 15 Participants |
| Primary Disease Lymphoma | 17 Participants | 5 Participants | 22 Participants |
| Primary Disease MDS / MPS | 9 Participants | 12 Participants | 21 Participants |
| Primary Disease Other | 7 Participants | 1 Participants | 8 Participants |
| Race/Ethnicity, Customized Non-white | 9 Participants | 13 Participants | 22 Participants |
| Race/Ethnicity, Customized Unknown / Not Answered | 0 Participants | 5 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 57 Participants | 54 Participants | 111 Participants |
| Sex: Female, Male Female | 33 Participants | 24 Participants | 57 Participants |
| Sex: Female, Male Male | 33 Participants | 48 Participants | 81 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 16 / 66 | 13 / 72 |
| other Total, other adverse events | 0 / 66 | 0 / 72 |
| serious Total, serious adverse events | 13 / 66 | 12 / 72 |
Outcome results
Primary
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.
Time frame: 6 months and 24 months post-randomization
Population: 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 | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Proportion of Participants With Treatment Success | Phase II: 6 Months | Yes | 33 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Proportion of Participants With Treatment Success | Phase II: 6 Months | No | 33 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Proportion of Participants With Treatment Success | Phase III: 24 Months | Yes | 9 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Proportion of Participants With Treatment Success | Phase III: 24 Months | No | 49 Participants |
| Sirolimus and Prednisone | Proportion of Participants With Treatment Success | Phase III: 24 Months | No | 58 Participants |
| Sirolimus and Prednisone | Proportion of Participants With Treatment Success | Phase II: 6 Months | Yes | 35 Participants |
| Sirolimus and Prednisone | Proportion of Participants With Treatment Success | Phase III: 24 Months | Yes | 10 Participants |
| Sirolimus and Prednisone | Proportion of Participants With Treatment Success | Phase II: 6 Months | No | 37 Participants |
Comparison: 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.p-value: 0.63Fisher Exact
Comparison: 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.p-value: 0.44Fisher Exact
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.
Time frame: 6 months and 1 year post-randomization
Population: Outcomes are analyzed in participants that were alive and completed assessments.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Change in Prednisone Dose From Baseline | 6 Months | -0.6 mg/kg/day |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Change in Prednisone Dose From Baseline | 1 Year | -0.6 mg/kg/day |
| Sirolimus and Prednisone | Change in Prednisone Dose From Baseline | 6 Months | -0.6 mg/kg/day |
| Sirolimus and Prednisone | Change in Prednisone Dose From Baseline | 1 Year | -0.7 mg/kg/day |
Comparison: 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.p-value: 0.586Kruskal-Wallis
Comparison: 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.p-value: 0.14Kruskal-Wallis
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.
Time frame: 6 months and 1 year post-randomization
Population: Outcomes are analyzed in participants that were alive and completed assessments.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Change in Serum Creatinine Level From Baseline | 6 Months | 0.1 mg/dL |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Change in Serum Creatinine Level From Baseline | 1 Year | 0.0 mg/dL |
| Sirolimus and Prednisone | Change in Serum Creatinine Level From Baseline | 6 Months | 0.1 mg/dL |
| Sirolimus and Prednisone | Change in Serum Creatinine Level From Baseline | 1 Year | 0.0 mg/dL |
Comparison: 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.p-value: 0.147Kruskal-Wallis
Comparison: 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.p-value: 0.863Kruskal-Wallis
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.
Time frame: Baseline, 2 months, 6 months, 1 year, and 2 years post-randomization
Population: Outcomes are analyzed in participants that were alive and completed assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sirolimus, Calcineurin Inhibitor, and Prednisone | FACT-BMT Score | 2 Months | 105 score on a scale | Standard Error 2.8 |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | FACT-BMT Score | 1 Year | 114 score on a scale | Standard Error 2.6 |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | FACT-BMT Score | 6 Months | 109 score on a scale | Standard Error 3.2 |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | FACT-BMT Score | 2 Years | 119 score on a scale | Standard Error 3.8 |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | FACT-BMT Score | Baseline | 103 score on a scale | Standard Error 2.6 |
| Sirolimus and Prednisone | FACT-BMT Score | 2 Years | 113 score on a scale | Standard Error 3.7 |
| Sirolimus and Prednisone | FACT-BMT Score | Baseline | 104 score on a scale | Standard Error 2.5 |
| Sirolimus and Prednisone | FACT-BMT Score | 2 Months | 110 score on a scale | Standard Error 2.4 |
| Sirolimus and Prednisone | FACT-BMT Score | 6 Months | 109 score on a scale | Standard Error 3.4 |
| Sirolimus and Prednisone | FACT-BMT Score | 1 Year | 110 score on a scale | Standard Error 3.6 |
Comparison: 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.p-value: 0.763t-test, 2 sided
Comparison: 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.p-value: 0.133t-test, 2 sided
Comparison: 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.p-value: 0.953t-test, 2 sided
Comparison: 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.p-value: 0.398t-test, 2 sided
Comparison: 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.p-value: 0.309t-test, 2 sided
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.
Time frame: Baseline, 6 months, 1 year, and 2 years post-randomization
Population: Outcomes are analyzed in participants that were alive and whose clinical assessments were completed.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 1 Year | None | 2 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | Baseline | Relapsed | 0 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 1 Year | Mild | 2 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 6 Months | Mild | 3 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 1 Year | Moderate | 16 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | Baseline | Mild | 1 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 1 Year | Severe | 9 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 6 Months | Moderate | 25 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 1 Year | Relapsed | 5 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | Baseline | Initiated Secondary Therapy | 0 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 1 Year | Initiated Secondary Therapy | 15 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 6 Months | Severe | 12 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 1 Year | Dead | 7 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | Baseline | Severe | 33 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 2 Years | None | 9 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 6 Months | Relapsed | 3 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 2 Years | Mild | 6 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | Baseline | Dead | 0 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 2 Years | Moderate | 8 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 6 Months | Initiated Secondary Therapy | 7 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 2 Years | Severe | 2 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | Baseline | Moderate | 29 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 2 Years | Relapsed | 8 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 6 Months | Dead | 6 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 2 Years | Initiated Secondary Therapy | 18 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 6 Months | None | 3 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 2 Years | Dead | 7 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | Baseline | None | 0 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 2 Years | Dead | 4 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | Baseline | None | 1 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | Baseline | Mild | 1 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | Baseline | Moderate | 23 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | Baseline | Severe | 46 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | Baseline | Relapsed | 0 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | Baseline | Initiated Secondary Therapy | 0 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | Baseline | Dead | 0 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 6 Months | None | 1 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 6 Months | Mild | 3 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 6 Months | Moderate | 27 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 6 Months | Severe | 17 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 6 Months | Relapsed | 1 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 6 Months | Initiated Secondary Therapy | 14 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 6 Months | Dead | 4 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 1 Year | None | 3 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 1 Year | Mild | 5 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 1 Year | Moderate | 16 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 1 Year | Severe | 10 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 1 Year | Relapsed | 3 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 1 Year | Initiated Secondary Therapy | 21 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 1 Year | Dead | 4 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 2 Years | None | 9 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 2 Years | Mild | 12 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 2 Years | Moderate | 8 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 2 Years | Severe | 2 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 2 Years | Relapsed | 5 Participants |
| Sirolimus and Prednisone | NIH Consensus Criteria Chronic GVHD Severity | 2 Years | Initiated Secondary Therapy | 28 Participants |
Comparison: 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.p-value: 0.238Fisher Exact
Comparison: 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.p-value: 0.546Fisher Exact
Comparison: 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.p-value: 0.756Fisher Exact
Comparison: 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.p-value: 0.554Fisher Exact
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.
Time frame: Baseline, 6 months, 1 year, and 2 years post-randomization
Population: Outcomes are analyzed in participants that were alive and completed assessments.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 1 Year | None | 9 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | Baseline | Relapsed | 0 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 1 Year | Mild | 13 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 6 Months | Mild | 13 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 1 Year | Moderate | 4 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | Baseline | Mild | 21 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 1 Year | Severe | 0 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 6 Months | Moderate | 15 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 1 Year | Relapsed | 5 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | Baseline | Initiated Secondary Therapy | 0 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 1 Year | Initiated Secondary Therapy | 15 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 6 Months | Severe | 2 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 1 Year | Dead | 7 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | Baseline | Severe | 10 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 2 Years | None | 2 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 6 Months | Relapsed | 3 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 2 Years | Mild | 10 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | Baseline | Dead | 0 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 2 Years | Moderate | 2 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 6 Months | Initiated Secondary Therapy | 7 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 2 Years | Severe | 0 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | Baseline | Moderate | 23 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 2 Years | Relapsed | 8 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 6 Months | Dead | 6 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 2 Years | Initiated Secondary Therapy | 18 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 6 Months | None | 4 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | 2 Years | Dead | 7 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Patient-reported Chronic GVHD Severity | Baseline | None | 0 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 2 Years | Dead | 4 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | Baseline | None | 0 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | Baseline | Mild | 20 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | Baseline | Moderate | 32 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | Baseline | Severe | 10 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | Baseline | Relapsed | 0 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | Baseline | Initiated Secondary Therapy | 0 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | Baseline | Dead | 0 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 6 Months | None | 6 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 6 Months | Mild | 25 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 6 Months | Moderate | 10 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 6 Months | Severe | 3 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 6 Months | Relapsed | 1 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 6 Months | Initiated Secondary Therapy | 14 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 6 Months | Dead | 4 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 1 Year | None | 2 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 1 Year | Mild | 23 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 1 Year | Moderate | 3 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 1 Year | Severe | 4 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 1 Year | Relapsed | 3 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 1 Year | Initiated Secondary Therapy | 21 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 1 Year | Dead | 4 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 2 Years | None | 6 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 2 Years | Mild | 13 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 2 Years | Moderate | 1 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 2 Years | Severe | 0 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 2 Years | Relapsed | 5 Participants |
| Sirolimus and Prednisone | Patient-reported Chronic GVHD Severity | 2 Years | Initiated Secondary Therapy | 28 Participants |
Comparison: 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.p-value: 0.62Fisher Exact
Comparison: 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.p-value: 0.258Fisher Exact
Comparison: 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.p-value: 0.036Fisher Exact
Comparison: 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.p-value: 0.369Fisher Exact
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.
Time frame: 2 years post-randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Percentage of Participants With Discontinuation of Systemic Immunosuppressive Therapy at Two Years | 20 percentage of participants |
| Sirolimus and Prednisone | Percentage of Participants With Discontinuation of Systemic Immunosuppressive Therapy at Two Years | 23.2 percentage of participants |
Comparison: 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.p-value: 0.706Gray's test
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.
Time frame: 6 months and 24 months post-randomization
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Percentage of Participants With Failure-free Survival | 6 Months | 74.7 percentage of participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Percentage of Participants With Failure-free Survival | 24 Months | 46.2 percentage of participants |
| Sirolimus and Prednisone | Percentage of Participants With Failure-free Survival | 6 Months | 73.6 percentage of participants |
| Sirolimus and Prednisone | Percentage of Participants With Failure-free Survival | 24 Months | 48.6 percentage of participants |
Comparison: 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.p-value: 0.775Log Rank
Secondary
Percentage of Participants With Overall Survival
Overall survival is defined as survival of death from any cause.
Time frame: 6 months and 24 months post-randomization
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Percentage of Participants With Overall Survival | 6 Months | 85.5 percentage of participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Percentage of Participants With Overall Survival | 24 Months | 74.0 percentage of participants |
| Sirolimus and Prednisone | Percentage of Participants With Overall Survival | 6 Months | 91.7 percentage of participants |
| Sirolimus and Prednisone | Percentage of Participants With Overall Survival | 24 Months | 81.5 percentage of participants |
Comparison: 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.p-value: 0.205Log Rank
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.
Time frame: 6 months and 24 months post-randomization
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Percentage of Participants With Progression-free Survival | 6 Months | 84.0 percentage of participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Percentage of Participants With Progression-free Survival | 24 Months | 67.3 percentage of participants |
| Sirolimus and Prednisone | Percentage of Participants With Progression-free Survival | 6 Months | 90.3 percentage of participants |
| Sirolimus and Prednisone | Percentage of Participants With Progression-free Survival | 24 Months | 78.6 percentage of participants |
Comparison: 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.p-value: 0.141Log Rank
Secondary
Percentage of Participants With Relapse
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Percentage of Participants With Relapse | 6 Months | 4.8 percentage of participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Percentage of Participants With Relapse | 24 Months | 14.9 percentage of participants |
| Sirolimus and Prednisone | Percentage of Participants With Relapse | 6 Months | 1.4 percentage of participants |
| Sirolimus and Prednisone | Percentage of Participants With Relapse | 24 Months | 10.1 percentage of participants |
Comparison: 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.p-value: 0.396Gray's test
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.
Time frame: 6 months and 24 months post-randomization
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Percentage of Participants With Secondary Immunosuppressive Therapy Initiated | 6 Months | 12.9 percentage of participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Percentage of Participants With Secondary Immunosuppressive Therapy Initiated | 24 months | 29.4 percentage of participants |
| Sirolimus and Prednisone | Percentage of Participants With Secondary Immunosuppressive Therapy Initiated | 6 Months | 13.9 percentage of participants |
| Sirolimus and Prednisone | Percentage of Participants With Secondary Immunosuppressive Therapy Initiated | 24 months | 38.5 percentage of participants |
Comparison: 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.p-value: 0.219Gray's test
Secondary
Prednisone Dose
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
Population: Outcomes are analyzed in participants that were alive and completed assessments.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Prednisone Dose | Baseline | 0.9 mg/kg/day |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Prednisone Dose | 6 Months | 0.2 mg/kg/day |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Prednisone Dose | 1 Year | 0.2 mg/kg/day |
| Sirolimus and Prednisone | Prednisone Dose | Baseline | 0.9 mg/kg/day |
| Sirolimus and Prednisone | Prednisone Dose | 6 Months | 0.2 mg/kg/day |
| Sirolimus and Prednisone | Prednisone Dose | 1 Year | 0.1 mg/kg/day |
Comparison: 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.p-value: 0.127Kruskal-Wallis
Comparison: 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.p-value: 0.562Kruskal-Wallis
Comparison: 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.p-value: 0.129Kruskal-Wallis
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.
Time frame: Baseline, 6 months, 1 year, and 2 years post-randomization
Population: Outcomes are analyzed in participants that were alive and whose providers completed assessments.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 1 Year | None | 8 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | Baseline | Relapsed | 0 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 1 Year | Mild | 15 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 6 Months | Mild | 27 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 1 Year | Moderate | 5 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | Baseline | Mild | 13 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 1 Year | Severe | 1 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 6 Months | Moderate | 10 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 1 Year | Relapsed | 5 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | Baseline | Initiated Secondary Therapy | 0 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 1 Year | Initiated Secondary Therapy | 15 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 6 Months | Severe | 0 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 1 Year | Dead | 7 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | Baseline | Severe | 3 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 2 Years | None | 7 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 6 Months | Relapsed | 3 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 2 Years | Mild | 10 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | Baseline | Dead | 0 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 2 Years | Moderate | 1 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 6 Months | Initiated Secondary Therapy | 7 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 2 Years | Severe | 0 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | Baseline | Moderate | 46 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 2 Years | Relapsed | 8 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 6 Months | Dead | 6 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 2 Years | Initiated Secondary Therapy | 18 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 6 Months | None | 6 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | 2 Years | Dead | 7 Participants |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Provider-reported Chronic GVHD Severity | Baseline | None | 1 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 2 Years | Dead | 4 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | Baseline | None | 0 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | Baseline | Mild | 17 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | Baseline | Moderate | 48 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | Baseline | Severe | 7 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | Baseline | Relapsed | 0 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | Baseline | Initiated Secondary Therapy | 0 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | Baseline | Dead | 0 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 6 Months | None | 2 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 6 Months | Mild | 33 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 6 Months | Moderate | 13 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 6 Months | Severe | 0 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 6 Months | Relapsed | 1 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 6 Months | Initiated Secondary Therapy | 14 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 6 Months | Dead | 4 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 1 Year | None | 7 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 1 Year | Mild | 19 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 1 Year | Moderate | 9 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 1 Year | Severe | 1 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 1 Year | Relapsed | 3 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 1 Year | Initiated Secondary Therapy | 21 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 1 Year | Dead | 4 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 2 Years | None | 7 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 2 Years | Mild | 11 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 2 Years | Moderate | 4 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 2 Years | Severe | 0 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 2 Years | Relapsed | 5 Participants |
| Sirolimus and Prednisone | Provider-reported Chronic GVHD Severity | 2 Years | Initiated Secondary Therapy | 28 Participants |
Comparison: 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.p-value: 0.45Fisher Exact
Comparison: 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.p-value: 0.301Fisher Exact
Comparison: 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.p-value: 0.75Fisher Exact
Comparison: 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.p-value: 0.444Fisher Exact
Secondary
Serum Creatinine Level
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
Population: Outcomes are analyzed in participants that were alive and completed assessments.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Serum Creatinine Level | Baseline | 0.9 mg/dL |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Serum Creatinine Level | 6 Months | 1.0 mg/dL |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | Serum Creatinine Level | 1 Year | 0.9 mg/dL |
| Sirolimus and Prednisone | Serum Creatinine Level | Baseline | 0.9 mg/dL |
| Sirolimus and Prednisone | Serum Creatinine Level | 6 Months | 1.0 mg/dL |
| Sirolimus and Prednisone | Serum Creatinine Level | 1 Year | 0.9 mg/dL |
Comparison: 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.p-value: 0.582Kruskal-Wallis
Comparison: 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.p-value: 0.208Kruskal-Wallis
Comparison: 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.p-value: 0.431Kruskal-Wallis
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.
Time frame: Baseline, 2 months, 6 months, 1 year, and 2 years post-randomization
Population: Outcomes are analyzed in participants that were alive and completed assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sirolimus, Calcineurin Inhibitor, and Prednisone | SF-36 Mental Component Summary | Baseline | 47 score on a scale | Standard Error 1.3 |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | SF-36 Mental Component Summary | 1 Year | 50 score on a scale | Standard Error 1.7 |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | SF-36 Mental Component Summary | 2 Months | 49 score on a scale | Standard Error 1.4 |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | SF-36 Mental Component Summary | 2 Years | 52 score on a scale | Standard Error 1.7 |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | SF-36 Mental Component Summary | 6 Months | 50 score on a scale | Standard Error 1.5 |
| Sirolimus and Prednisone | SF-36 Mental Component Summary | 2 Years | 50 score on a scale | Standard Error 1.6 |
| Sirolimus and Prednisone | SF-36 Mental Component Summary | Baseline | 48 score on a scale | Standard Error 1.4 |
| Sirolimus and Prednisone | SF-36 Mental Component Summary | 6 Months | 48 score on a scale | Standard Error 1.6 |
| Sirolimus and Prednisone | SF-36 Mental Component Summary | 1 Year | 46 score on a scale | Standard Error 2.1 |
| Sirolimus and Prednisone | SF-36 Mental Component Summary | 2 Months | 50 score on a scale | Standard Error 1.5 |
Comparison: 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.p-value: 0.631t-test, 2 sided
Comparison: 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.p-value: 0.759t-test, 2 sided
Comparison: 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.p-value: 0.391t-test, 2 sided
Comparison: 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.p-value: 0.222t-test, 2 sided
Comparison: 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.p-value: 0.527t-test, 2 sided
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.
Time frame: Baseline, 2 months, 6 months, 1 year, and 2 years post-randomization
Population: Outcomes are analyzed in participants that were alive and completed assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sirolimus, Calcineurin Inhibitor, and Prednisone | SF-36 Physical Component Summary | 2 Months | 39 score on a scale | Standard Error 1.6 |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | SF-36 Physical Component Summary | 1 Year | 40 score on a scale | Standard Error 1.8 |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | SF-36 Physical Component Summary | 6 Months | 38 score on a scale | Standard Error 2.1 |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | SF-36 Physical Component Summary | 2 Years | 44 score on a scale | Standard Error 2.4 |
| Sirolimus, Calcineurin Inhibitor, and Prednisone | SF-36 Physical Component Summary | Baseline | 38 score on a scale | Standard Error 1.3 |
| Sirolimus and Prednisone | SF-36 Physical Component Summary | 2 Years | 43 score on a scale | Standard Error 2 |
| Sirolimus and Prednisone | SF-36 Physical Component Summary | Baseline | 38 score on a scale | Standard Error 1.2 |
| Sirolimus and Prednisone | SF-36 Physical Component Summary | 2 Months | 42 score on a scale | Standard Error 1.6 |
| Sirolimus and Prednisone | SF-36 Physical Component Summary | 6 Months | 43 score on a scale | Standard Error 1.5 |
| Sirolimus and Prednisone | SF-36 Physical Component Summary | 1 Year | 43 score on a scale | Standard Error 1.7 |
Comparison: 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.p-value: 0.685t-test, 2 sided
Comparison: 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.p-value: 0.105t-test, 2 sided
Comparison: 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.p-value: 0.039t-test, 2 sided
Comparison: 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.p-value: 0.278t-test, 2 sided
Comparison: 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.p-value: 0.804t-test, 2 sided