Trial Outcomes & Findings for Sirolimus, Cyclosporine, and Mycophenolate Mofetil in Preventing Graft-versus-Host Disease in Treating Patients With Blood Cancer Undergoing Donor Peripheral Blood Stem Cell Transplant (NCT NCT01251575)
NCT ID: NCT01251575
Last Updated: 2019-12-09
Results Overview
Number of patients with grades II-IV acute GVHD aGVHD Stages Skin: 1. a maculopapular eruption involving \< 25% BSA 2. a maculopapular eruption involving 25 - 50% BSA 3. generalized erythroderma 4. generalized erythroderma w/ bullous formation and often w/ desquamation Liver: 1. bilirubin 2.0 - 3.0 mg/100 mL 2. bilirubin 3 - 5.9 mg/100 mL 3. bilirubin 6 - 14.9 mg/100 mL 4. bilirubin \> 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients w/ visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade II: Stage 1 - 2 skin w/ no gut/liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 w/ extreme constitutional symptoms or death
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
77 participants
Primary outcome timeframe
100 days post-transplant
Results posted on
2019-12-09
Participant Flow
Participant milestones
| Measure |
Treatment (Fludarabine, Transplant, Immunosuppression)
CONDITIONING: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2. Patients also undergo total-body irradiation on day 0.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation.
IMMUNOSUPPRESSION: Patients receive sirolimus PO QD on days -3 to 180 with taper to day 365; cyclosporine PO BID on days -3 to 150 with taper to day 180; and mycophenolate mofetil PO TID on days 0-30 and then BID to day 100 with taper to day 150.
Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant
Cyclosporine: Given PO or IV
Fludarabine Phosphate: Given IV
Laboratory Biomarker Analysis: Correlative studies
Mycophenolate Mofetil: Given PO
Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant
Sirolimus: Given PO
Total-Body Irradiation: Undergo total-body irradiation
|
|---|---|
|
Overall Study
STARTED
|
77
|
|
Overall Study
COMPLETED
|
76
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Sirolimus, Cyclosporine, and Mycophenolate Mofetil in Preventing Graft-versus-Host Disease in Treating Patients With Blood Cancer Undergoing Donor Peripheral Blood Stem Cell Transplant
Baseline characteristics by cohort
| Measure |
Treatment (Fludarabine, Transplant, Immunosuppression)
n=77 Participants
CONDITIONING: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2. Patients also undergo total-body irradiation on day 0.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation.
IMMUNOSUPPRESSION: Patients receive sirolimus PO QD on days -3 to 180 with taper to day 365; cyclosporine PO BID on days -3 to 150 with taper to day 180; and mycophenolate mofetil PO TID on days 0-30 and then BID to day 100 with taper to day 150.
Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant
Cyclosporine: Given PO or IV
Fludarabine Phosphate: Given IV
Laboratory Biomarker Analysis: Correlative studies
Mycophenolate Mofetil: Given PO
Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant
Sirolimus: Given PO
Total-Body Irradiation: Undergo total-body irradiation
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
45 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
32 Participants
n=93 Participants
|
|
Age, Continuous
|
63.8 years
n=93 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
50 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
8 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
67 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
65 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
60 participants
n=93 Participants
|
|
Region of Enrollment
Denmark
|
17 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 100 days post-transplantNumber of patients with grades II-IV acute GVHD aGVHD Stages Skin: 1. a maculopapular eruption involving \< 25% BSA 2. a maculopapular eruption involving 25 - 50% BSA 3. generalized erythroderma 4. generalized erythroderma w/ bullous formation and often w/ desquamation Liver: 1. bilirubin 2.0 - 3.0 mg/100 mL 2. bilirubin 3 - 5.9 mg/100 mL 3. bilirubin 6 - 14.9 mg/100 mL 4. bilirubin \> 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients w/ visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade II: Stage 1 - 2 skin w/ no gut/liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 w/ extreme constitutional symptoms or death
Outcome measures
| Measure |
Class I Mismatch
n=51 Participants
Patients 1) mismatched at antigen level for any single class I locus (HLA-A, -B, -C) +/- an additional class mismatch at the allele level, or 2) mismatched at the allele level for any 2 class I loci.
|
Class II Mismatch
n=25 Participants
Patients mismatched at the antigen or allele level for class II loci HLA-DRB1 and/or DQB1. Must be matched for at least one DRB1 allele and one DQB1 allele.
|
|---|---|---|
|
Number of Patients With Grade II-IV Acute Graft Versus Host Disease (GVHD)
|
15 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: 100 days post-transplantPopulation: One subject aborted transplant during conditioning and was counted towards accrual but not evaluated with respect to outcome measures.
Number of patients expired without disease progression/relapse.
Outcome measures
| Measure |
Class I Mismatch
n=76 Participants
Patients 1) mismatched at antigen level for any single class I locus (HLA-A, -B, -C) +/- an additional class mismatch at the allele level, or 2) mismatched at the allele level for any 2 class I loci.
|
Class II Mismatch
Patients mismatched at the antigen or allele level for class II loci HLA-DRB1 and/or DQB1. Must be matched for at least one DRB1 allele and one DQB1 allele.
|
|---|---|---|
|
Number of Non-Relapse Mortalities
|
3 Participants
|
—
|
SECONDARY outcome
Timeframe: 100 days post-transplantPopulation: One subject aborted transplant during conditioning and was counted towards accrual but not evaluated with respect to outcome measures.
Number of patients with grades III-IV acute GVHD aGVHD Stages Skin: 1. a maculopapular eruption involving \< 25% BSA 2. a maculopapular eruption involving 25 - 50% BSA 3. generalized erythroderma 4. generalized erythroderma w/ bullous formation and often w/ desquamation Liver: 1. bilirubin 2.0 - 3.0 mg/100 mL 2. bilirubin 3 - 5.9 mg/100 mL 3. bilirubin 6 - 14.9 mg/100 mL 4. bilirubin \> 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients w/ visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade II: Stage 1 - 2 skin w/ no gut/liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 w/ extreme constitutional symptoms or death
Outcome measures
| Measure |
Class I Mismatch
n=76 Participants
Patients 1) mismatched at antigen level for any single class I locus (HLA-A, -B, -C) +/- an additional class mismatch at the allele level, or 2) mismatched at the allele level for any 2 class I loci.
|
Class II Mismatch
Patients mismatched at the antigen or allele level for class II loci HLA-DRB1 and/or DQB1. Must be matched for at least one DRB1 allele and one DQB1 allele.
|
|---|---|---|
|
Number of Patients With Grade III-IV Acute GVHD
|
2 Participants
|
—
|
Adverse Events
Treatment (Fludarabine, Transplant, Immunosuppression)
Serious events: 0 serious events
Other events: 25 other events
Deaths: 21 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment (Fludarabine, Transplant, Immunosuppression)
n=76 participants at risk
CONDITIONING: Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2. Patients also undergo total-body irradiation on day 0.
TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation.
IMMUNOSUPPRESSION: Patients receive sirolimus PO QD on days -3 to 180 with taper to day 365; cyclosporine PO BID on days -3 to 150 with taper to day 180; and mycophenolate mofetil PO TID on days 0-30 and then BID to day 100 with taper to day 150.
Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant
Cyclosporine: Given PO or IV
Fludarabine Phosphate: Given IV
Laboratory Biomarker Analysis: Correlative studies
Mycophenolate Mofetil: Given PO
Peripheral Blood Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant
Sirolimus: Given PO
Total-Body Irradiation: Undergo total-body irradiation
|
|---|---|
|
Renal and urinary disorders
Acute kidney injury
|
5.3%
4/76 • Number of events 4 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Gastrointestinal disorders
Ascites
|
1.3%
1/76 • Number of events 1 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Cardiac disorders
Atrial fibrillation
|
1.3%
1/76 • Number of events 1 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Cardiac disorders
Atrial flutter
|
1.3%
1/76 • Number of events 1 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Investigations
Blood bilirubin increased
|
3.9%
3/76 • Number of events 3 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage
|
2.6%
2/76 • Number of events 2 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Renal and urinary disorders
Chronic kidney disease
|
2.6%
2/76 • Number of events 2 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Investigations
Creatinine increased
|
3.9%
3/76 • Number of events 3 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Gastrointestinal disorders
Diarrhea
|
3.9%
3/76 • Number of events 3 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Investigations
Ejection fraction decreased
|
1.3%
1/76 • Number of events 1 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Infections and infestations
Encephalitis infection
|
1.3%
1/76 • Number of events 1 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
5.3%
4/76 • Number of events 4 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Gastrointestinal disorders
Gastric hemorrhage
|
1.3%
1/76 • Number of events 1 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Gastrointestinal disorders
Gastritis
|
1.3%
1/76 • Number of events 1 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Cardiac disorders
Heart failure
|
1.3%
1/76 • Number of events 1 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Blood and lymphatic system disorders
Hemolysis
|
1.3%
1/76 • Number of events 1 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Blood and lymphatic system disorders
Hemolytic uremic syndrome
|
1.3%
1/76 • Number of events 1 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Vascular disorders
Hypotension
|
2.6%
2/76 • Number of events 2 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
5.3%
4/76 • Number of events 4 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Cardiac disorders
Left ventricular systolic dysfunction
|
2.6%
2/76 • Number of events 2 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Infections and infestations
Lung infection
|
2.6%
2/76 • Number of events 2 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Gastrointestinal disorders
Mucositis oral
|
1.3%
1/76 • Number of events 1 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
General disorders
Multi-organ failure
|
1.3%
1/76 • Number of events 2 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
1.3%
1/76 • Number of events 1 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Cardiac disorders
Paroxysmal atrial tachycardia
|
1.3%
1/76 • Number of events 1 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.3%
1/76 • Number of events 1 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.3%
1/76 • Number of events 1 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Infections and infestations
Sepsis
|
3.9%
3/76 • Number of events 4 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Infections and infestations
Small intestine infection
|
1.3%
1/76 • Number of events 1 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Nervous system disorders
Syncope
|
1.3%
1/76 • Number of events 1 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Vascular disorders
Thromboembolic event
|
2.6%
2/76 • Number of events 3 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Treatment related secondary malignancy
|
1.3%
1/76 • Number of events 1 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
Gastrointestinal disorders
Typhlitis
|
1.3%
1/76 • Number of events 1 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
|
General disorders
Fever
|
1.3%
1/76 • Number of events 2 • AEs: From the start of conditioning to 100 Days post-transplant SAEs: From the start of conditioning to 200 Days post-transplant All-Cause Mortality: Conditioning through 1 Year
|
Additional Information
Dr. Brenda M. Sandmaier
Fred Hutchinson Cancer Research Center
Phone: (206) 667-4961
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place