Trial Outcomes & Findings for Reduced Intensity Regimen vs Myeloablative Regimen for Myeloid Leukemia or Myelodysplastic Syndrome (BMT CTN 0901) (NCT NCT01339910)
NCT ID: NCT01339910
Last Updated: 2023-01-04
Results Overview
Overall survival is defined as survival of death from any cause.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
272 participants
Primary outcome timeframe
18 months post-randomization
Results posted on
2023-01-04
Participant Flow
Participants were enrolled between June 2011 and April 2014 from 32 transplant centers
Participant milestones
| Measure |
Myeloablative Conditioning Regimen (MAC)
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Busulfan and Fludarabine: (Bu/Flu)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)
Busulfan and Cyclophosphamide: (Bu/Cy)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
|
Reduced Intensity Conditioning (RIC)
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Fludarabine and Busulfan: (Flu/Bu)
* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Fludarabine and Melphalan: (Flu/Mel)
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2
|
|---|---|---|
|
Overall Study
STARTED
|
135
|
137
|
|
Overall Study
COMPLETED
|
132
|
133
|
|
Overall Study
NOT COMPLETED
|
3
|
4
|
Reasons for withdrawal
| Measure |
Myeloablative Conditioning Regimen (MAC)
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Busulfan and Fludarabine: (Bu/Flu)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)
Busulfan and Cyclophosphamide: (Bu/Cy)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
|
Reduced Intensity Conditioning (RIC)
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Fludarabine and Busulfan: (Flu/Bu)
* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Fludarabine and Melphalan: (Flu/Mel)
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Disease relapse
|
1
|
4
|
Baseline Characteristics
Participants with MDS
Baseline characteristics by cohort
| Measure |
Myeloablative Conditioning Regimen (MAC)
n=135 Participants
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Busulfan and Fludarabine: (Bu/Flu)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)
Busulfan and Cyclophosphamide: (Bu/Cy)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
|
Reduced Intensity Conditioning (RIC)
n=137 Participants
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Fludarabine and Busulfan: (Flu/Bu)
* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Fludarabine and Melphalan: (Flu/Mel)
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2
|
Total
n=272 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
54.8 years
n=135 Participants
|
54.8 years
n=137 Participants
|
54.8 years
n=272 Participants
|
|
Sex: Female, Male
Female
|
59 Participants
n=135 Participants
|
70 Participants
n=137 Participants
|
129 Participants
n=272 Participants
|
|
Sex: Female, Male
Male
|
76 Participants
n=135 Participants
|
67 Participants
n=137 Participants
|
143 Participants
n=272 Participants
|
|
Primary Disease
Acute Myeloid Leukemia (AML)
|
108 Participants
n=135 Participants
|
110 Participants
n=137 Participants
|
218 Participants
n=272 Participants
|
|
Primary Disease
Myelodysplastic Syndrome (MDS)
|
27 Participants
n=135 Participants
|
27 Participants
n=137 Participants
|
54 Participants
n=272 Participants
|
|
MDS WHO Classification
RA/RARS/RCMD/RCMD-RS/Del-5q/MDS-U
|
16 Participants
n=27 Participants • Participants with MDS
|
17 Participants
n=27 Participants • Participants with MDS
|
33 Participants
n=54 Participants • Participants with MDS
|
|
MDS WHO Classification
RAEB-1
|
5 Participants
n=27 Participants • Participants with MDS
|
5 Participants
n=27 Participants • Participants with MDS
|
10 Participants
n=54 Participants • Participants with MDS
|
|
MDS WHO Classification
RAEB-2
|
6 Participants
n=27 Participants • Participants with MDS
|
5 Participants
n=27 Participants • Participants with MDS
|
11 Participants
n=54 Participants • Participants with MDS
|
|
AML WHO Classification
AML with recurrent genetic abnormalities
|
12 Participants
n=108 Participants • Participants with AML
|
20 Participants
n=110 Participants • Participants with AML
|
32 Participants
n=218 Participants • Participants with AML
|
|
AML WHO Classification
AML with multilineage dysplasia
|
8 Participants
n=108 Participants • Participants with AML
|
12 Participants
n=110 Participants • Participants with AML
|
20 Participants
n=218 Participants • Participants with AML
|
|
AML WHO Classification
AML and MDS, therapy related
|
2 Participants
n=108 Participants • Participants with AML
|
3 Participants
n=110 Participants • Participants with AML
|
5 Participants
n=218 Participants • Participants with AML
|
|
AML WHO Classification
AML, not otherwise specified
|
86 Participants
n=108 Participants • Participants with AML
|
75 Participants
n=110 Participants • Participants with AML
|
161 Participants
n=218 Participants • Participants with AML
|
|
Disease Duration
|
6 months
n=135 Participants
|
6 months
n=137 Participants
|
6 months
n=272 Participants
|
|
Disease Risk Status
Standard
|
74 Participants
n=135 Participants
|
71 Participants
n=137 Participants
|
145 Participants
n=272 Participants
|
|
Disease Risk Status
High
|
54 Participants
n=135 Participants
|
61 Participants
n=137 Participants
|
115 Participants
n=272 Participants
|
|
Disease Risk Status
Unknown
|
7 Participants
n=135 Participants
|
5 Participants
n=137 Participants
|
12 Participants
n=272 Participants
|
|
HCT-CI
0
|
46 Participants
n=135 Participants
|
40 Participants
n=137 Participants
|
86 Participants
n=272 Participants
|
|
HCT-CI
1-2
|
45 Participants
n=135 Participants
|
52 Participants
n=137 Participants
|
97 Participants
n=272 Participants
|
|
HCT-CI
3 or more
|
42 Participants
n=135 Participants
|
44 Participants
n=137 Participants
|
86 Participants
n=272 Participants
|
|
HCT-CI
Unknown
|
2 Participants
n=135 Participants
|
1 Participants
n=137 Participants
|
3 Participants
n=272 Participants
|
|
Conditioning Regimen
Flu/Bu4
|
87 Participants
n=135 Participants
|
0 Participants
n=137 Participants
|
87 Participants
n=272 Participants
|
|
Conditioning Regimen
Bu/Cy
|
40 Participants
n=135 Participants
|
0 Participants
n=137 Participants
|
40 Participants
n=272 Participants
|
|
Conditioning Regimen
Cy/TBI
|
8 Participants
n=135 Participants
|
0 Participants
n=137 Participants
|
8 Participants
n=272 Participants
|
|
Conditioning Regimen
Flu/Mel
|
0 Participants
n=135 Participants
|
27 Participants
n=137 Participants
|
27 Participants
n=272 Participants
|
|
Conditioning Regimen
Flu/Bu2
|
0 Participants
n=135 Participants
|
110 Participants
n=137 Participants
|
110 Participants
n=272 Participants
|
|
GVHD Prophylaxis
Tacrolimus / Methotrexate
|
110 Participants
n=135 Participants
|
112 Participants
n=137 Participants
|
222 Participants
n=272 Participants
|
|
GVHD Prophylaxis
Cyclosporine / Methotrexate
|
3 Participants
n=135 Participants
|
3 Participants
n=137 Participants
|
6 Participants
n=272 Participants
|
|
GVHD Prophylaxis
TAC / Mycophenolate mofetil
|
8 Participants
n=135 Participants
|
5 Participants
n=137 Participants
|
13 Participants
n=272 Participants
|
|
GVHD Prophylaxis
Cyclosporine / Mycophenolate mofetil
|
1 Participants
n=135 Participants
|
0 Participants
n=137 Participants
|
1 Participants
n=272 Participants
|
|
GVHD Prophylaxis
Sirolimus / Tacrolimus
|
10 Participants
n=135 Participants
|
12 Participants
n=137 Participants
|
22 Participants
n=272 Participants
|
|
GVHD Prophylaxis
Other
|
3 Participants
n=135 Participants
|
5 Participants
n=137 Participants
|
8 Participants
n=272 Participants
|
|
ATG Use
Yes
|
18 Participants
n=135 Participants
|
22 Participants
n=137 Participants
|
40 Participants
n=272 Participants
|
|
ATG Use
No
|
117 Participants
n=135 Participants
|
115 Participants
n=137 Participants
|
232 Participants
n=272 Participants
|
|
Donor Type
Matched Related
|
57 Participants
n=135 Participants
|
58 Participants
n=137 Participants
|
115 Participants
n=272 Participants
|
|
Donor Type
Mismatched Related
|
2 Participants
n=135 Participants
|
5 Participants
n=137 Participants
|
7 Participants
n=272 Participants
|
|
Donor Type
Matched Unrelated
|
66 Participants
n=135 Participants
|
58 Participants
n=137 Participants
|
124 Participants
n=272 Participants
|
|
Donor Type
Mismatched Unrelated
|
10 Participants
n=135 Participants
|
16 Participants
n=137 Participants
|
26 Participants
n=272 Participants
|
|
Donor Source
Peripheral Blood
|
127 Participants
n=135 Participants
|
123 Participants
n=137 Participants
|
250 Participants
n=272 Participants
|
|
Donor Source
Bone Marrow
|
8 Participants
n=135 Participants
|
14 Participants
n=137 Participants
|
22 Participants
n=272 Participants
|
PRIMARY outcome
Timeframe: 18 months post-randomizationOverall survival is defined as survival of death from any cause.
Outcome measures
| Measure |
Reduced Intensity Conditioning (RIC)
n=137 Participants
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Fludarabine and Busulfan: (Flu/Bu)
* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Fludarabine and Melphalan: (Flu/Mel)
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2
|
Myeloablative Conditioning Regimen (MAC)
n=135 Participants
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Busulfan and Fludarabine: (Bu/Flu)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)
Busulfan and Cyclophosphamide: (Bu/Cy)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
|
|---|---|---|
|
Percentage of Participants With Overall Survival (OS)
|
67.7 percentage
Interval 59.1 to 74.9
|
77.5 percentage
Interval 69.4 to 83.7
|
SECONDARY outcome
Timeframe: 18 months post-randomizationRelapse-free survival is defined as survival without relapse of the primary disease.
Outcome measures
| Measure |
Reduced Intensity Conditioning (RIC)
n=137 Participants
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Fludarabine and Busulfan: (Flu/Bu)
* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Fludarabine and Melphalan: (Flu/Mel)
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2
|
Myeloablative Conditioning Regimen (MAC)
n=135 Participants
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Busulfan and Fludarabine: (Bu/Flu)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)
Busulfan and Cyclophosphamide: (Bu/Cy)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
|
|---|---|---|
|
Percentage of Participants With Relapse-Free Survival (RFS)
|
47.3 percentage
Interval 38.7 to 55.4
|
67.8 percentage
Interval 59.1 to 75.0
|
SECONDARY outcome
Timeframe: 18 months post-randomizationDisease Relapse is defined as relapse of the primary disease.
Outcome measures
| Measure |
Reduced Intensity Conditioning (RIC)
n=137 Participants
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Fludarabine and Busulfan: (Flu/Bu)
* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Fludarabine and Melphalan: (Flu/Mel)
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2
|
Myeloablative Conditioning Regimen (MAC)
n=135 Participants
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Busulfan and Fludarabine: (Bu/Flu)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)
Busulfan and Cyclophosphamide: (Bu/Cy)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
|
|---|---|---|
|
Percentage of Participants With Disease Relapse
|
48.3 percentage
Interval 39.6 to 56.4
|
13.5 percentage
Interval 8.3 to 19.8
|
SECONDARY outcome
Timeframe: 18 months post-randomizationTreatment-related mortality is defined as death without a previous relapse of the primary disease.
Outcome measures
| Measure |
Reduced Intensity Conditioning (RIC)
n=137 Participants
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Fludarabine and Busulfan: (Flu/Bu)
* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Fludarabine and Melphalan: (Flu/Mel)
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2
|
Myeloablative Conditioning Regimen (MAC)
n=135 Participants
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Busulfan and Fludarabine: (Bu/Flu)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)
Busulfan and Cyclophosphamide: (Bu/Cy)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
|
|---|---|---|
|
Percentage of Participants With Treatment-related Mortality
|
4.4 percentage
Interval 1.8 to 8.9
|
15.8 percentage
Interval 10.2 to 22.5
|
SECONDARY outcome
Timeframe: Days 28 and 60 post-transplantPopulation: Transplanted participants
Neutrophil engraftment is defined as achieving an absolute neutrophil count greater than 500x10\^6/liter for 3 consecutive measurements on different days. The first of the 3 days will be designated the day of neutrophil engraftment. Platelet engraftment is defined as achieving platelet counts greater than 20,000/microliter for consecutive measurements over 7 days without requiring platelet transfusions. The first of the 7 days will be designated the day of platelet engraftment. Subjects must not have had platelet transfusions during the preceding 7 days.
Outcome measures
| Measure |
Reduced Intensity Conditioning (RIC)
n=133 Participants
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Fludarabine and Busulfan: (Flu/Bu)
* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Fludarabine and Melphalan: (Flu/Mel)
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2
|
Myeloablative Conditioning Regimen (MAC)
n=132 Participants
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Busulfan and Fludarabine: (Bu/Flu)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)
Busulfan and Cyclophosphamide: (Bu/Cy)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
|
|---|---|---|
|
Percentage of Participants With Neutrophil and Platelet Engraftment
Neutrophil Engraftment at Day 28
|
97.8 percentage
|
98.5 percentage
|
|
Percentage of Participants With Neutrophil and Platelet Engraftment
Platelet Engraftment at Day 60
|
96.2 percentage
|
95.5 percentage
|
SECONDARY outcome
Timeframe: Days 28 and 100 and 18 months post-transplantPopulation: Transplanted participants
Donor cell engraftment will be assessed by donor-recipient chimerism assays. Full donor chimerism is defined as the presence of at least 95% donor cells as a proportion of the total population in the peripheral blood or bone marrow. Graft rejection is defined as the presence of no more than 5% donor cells as a proportion of the total population. Mixed chimerism is defined as the presence of between 5% and 95% donor cells. Mixed or full donor chimerism will be considered evidence of donor engraftment.
Outcome measures
| Measure |
Reduced Intensity Conditioning (RIC)
n=133 Participants
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Fludarabine and Busulfan: (Flu/Bu)
* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Fludarabine and Melphalan: (Flu/Mel)
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2
|
Myeloablative Conditioning Regimen (MAC)
n=132 Participants
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Busulfan and Fludarabine: (Bu/Flu)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)
Busulfan and Cyclophosphamide: (Bu/Cy)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
|
|---|---|---|
|
Number of Participants With Donor Cell Engraftment
Day 28 · Full Donor Chimerism
|
80 Participants
|
86 Participants
|
|
Number of Participants With Donor Cell Engraftment
Day 28 · Mixed Chimerism
|
30 Participants
|
9 Participants
|
|
Number of Participants With Donor Cell Engraftment
Day 28 · Graft Rejection
|
1 Participants
|
1 Participants
|
|
Number of Participants With Donor Cell Engraftment
Day 28 · Death Prior to Assessment
|
0 Participants
|
0 Participants
|
|
Number of Participants With Donor Cell Engraftment
Day 28 · Unknown (relapsed or missing assay)
|
22 Participants
|
36 Participants
|
|
Number of Participants With Donor Cell Engraftment
Day 100 · Full Donor Chimerism
|
86 Participants
|
106 Participants
|
|
Number of Participants With Donor Cell Engraftment
Day 100 · Mixed Chimerism
|
30 Participants
|
12 Participants
|
|
Number of Participants With Donor Cell Engraftment
Day 100 · Graft Rejection
|
1 Participants
|
2 Participants
|
|
Number of Participants With Donor Cell Engraftment
Day 100 · Death Prior to Assessment
|
8 Participants
|
6 Participants
|
|
Number of Participants With Donor Cell Engraftment
Day 100 · Unknown (relapsed or missing assay)
|
8 Participants
|
6 Participants
|
|
Number of Participants With Donor Cell Engraftment
18 Months · Full Donor Chimerism
|
66 Participants
|
71 Participants
|
|
Number of Participants With Donor Cell Engraftment
18 Months · Mixed Chimerism
|
5 Participants
|
4 Participants
|
|
Number of Participants With Donor Cell Engraftment
18 Months · Graft Rejection
|
1 Participants
|
1 Participants
|
|
Number of Participants With Donor Cell Engraftment
18 Months · Death Prior to Assessment
|
42 Participants
|
31 Participants
|
|
Number of Participants With Donor Cell Engraftment
18 Months · Unknown (relapsed or missing assay)
|
19 Participants
|
25 Participants
|
SECONDARY outcome
Timeframe: Day 100 post-transplantPopulation: Transplanted participants
Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash 1. Rash \<25% of body surface area 2. Rash on 25-50% of body surface area 3. Rash on \> 50% of body surface area 4. Generalized erythroderma with bullous formation Liver stage (based on bilirubin level)\*: 0: \<2 mg/dL 1. 2-3 mg/dL 2. 3.01-6 mg/dL 3. 6.01-15.0 mg/dL 4. \>15 mg/dL GI stage\*: 0: No diarrhea or diarrhea \<500 mL/day 1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD 2. Diarrhea 1000-1499 mL/day 3. Diarrhea \>1500 mL/day 4. Severe abdominal pain with or without ileus \* If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1. GVHD grade: 0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4
Outcome measures
| Measure |
Reduced Intensity Conditioning (RIC)
n=133 Participants
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Fludarabine and Busulfan: (Flu/Bu)
* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Fludarabine and Melphalan: (Flu/Mel)
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2
|
Myeloablative Conditioning Regimen (MAC)
n=132 Participants
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Busulfan and Fludarabine: (Bu/Flu)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)
Busulfan and Cyclophosphamide: (Bu/Cy)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
|
|---|---|---|
|
Percentage of Participants With Acute Graft Versus Host Disease (GVHD)
Grade II-IV Acute GVHD
|
31.6 percentage
Interval 23.8 to 39.6
|
44.7 percentage
Interval 36.0 to 53.0
|
|
Percentage of Participants With Acute Graft Versus Host Disease (GVHD)
Grade III-IV Acute GVHD
|
6.8 percentage
Interval 3.0 to 12.0
|
13.6 percentage
Interval 8.0 to 20.0
|
SECONDARY outcome
Timeframe: 18 months post-transplantPopulation: Transplanted participants
Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification.
Outcome measures
| Measure |
Reduced Intensity Conditioning (RIC)
n=133 Participants
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Fludarabine and Busulfan: (Flu/Bu)
* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Fludarabine and Melphalan: (Flu/Mel)
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2
|
Myeloablative Conditioning Regimen (MAC)
n=132 Participants
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Busulfan and Fludarabine: (Bu/Flu)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)
Busulfan and Cyclophosphamide: (Bu/Cy)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
|
|---|---|---|
|
Percentage of Participants With Chronic GVHD
|
47.6 percentage
Interval 38.8 to 58.8
|
64.0 percentage
Interval 55.0 to 71.7
|
SECONDARY outcome
Timeframe: 18 months post-transplantPopulation: Transplanted participants
Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe.
Outcome measures
| Measure |
Reduced Intensity Conditioning (RIC)
n=133 Participants
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Fludarabine and Busulfan: (Flu/Bu)
* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Fludarabine and Melphalan: (Flu/Mel)
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2
|
Myeloablative Conditioning Regimen (MAC)
n=132 Participants
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Busulfan and Fludarabine: (Bu/Flu)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)
Busulfan and Cyclophosphamide: (Bu/Cy)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
|
|---|---|---|
|
Number of Participants With Chronic GVHD Severity
Moderate
|
17 Participants
|
33 Participants
|
|
Number of Participants With Chronic GVHD Severity
None
|
70 Participants
|
47 Participants
|
|
Number of Participants With Chronic GVHD Severity
Mild
|
34 Participants
|
40 Participants
|
|
Number of Participants With Chronic GVHD Severity
Severe
|
12 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: 28 days post-transplantPopulation: Transplanted participants
Primary graft failure is defined by lack of neutrophil engraftment.
Outcome measures
| Measure |
Reduced Intensity Conditioning (RIC)
n=133 Participants
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Fludarabine and Busulfan: (Flu/Bu)
* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Fludarabine and Melphalan: (Flu/Mel)
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2
|
Myeloablative Conditioning Regimen (MAC)
n=132 Participants
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Busulfan and Fludarabine: (Bu/Flu)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)
Busulfan and Cyclophosphamide: (Bu/Cy)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
|
|---|---|---|
|
Number of Participants With Primary Graft Failure
|
3 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 18 months post-transplantPopulation: Transplanted participants
Secondary graft failure is defined by initial neutrophil engraftment followed by subsequent decline in neutrophil counts to less than 500x10\^6/liter that is unresponsive to growth factor therapy.
Outcome measures
| Measure |
Reduced Intensity Conditioning (RIC)
n=133 Participants
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Fludarabine and Busulfan: (Flu/Bu)
* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Fludarabine and Melphalan: (Flu/Mel)
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2
|
Myeloablative Conditioning Regimen (MAC)
n=132 Participants
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Busulfan and Fludarabine: (Bu/Flu)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)
Busulfan and Cyclophosphamide: (Bu/Cy)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
|
|---|---|---|
|
Number of Participants With Secondary Graft Failure
|
4 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 18 monthsPopulation: Transplanted participants
The maximum grade of toxicities reported by participants over the study duration are tabulated. Per the CTCAE criteria, toxicities are graded on a scale of 0-5, with higher numbers indicating greater severity. The categories correspond as follows: 3 - severe; 4 - life-threatening; 5 - fatal
Outcome measures
| Measure |
Reduced Intensity Conditioning (RIC)
n=133 Participants
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Fludarabine and Busulfan: (Flu/Bu)
* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Fludarabine and Melphalan: (Flu/Mel)
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2
|
Myeloablative Conditioning Regimen (MAC)
n=132 Participants
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Busulfan and Fludarabine: (Bu/Flu)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)
Busulfan and Cyclophosphamide: (Bu/Cy)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
|
|---|---|---|
|
Number of Participants With Maximum Grade 3-5 Toxicities
0-2
|
59 Participants
|
34 Participants
|
|
Number of Participants With Maximum Grade 3-5 Toxicities
3
|
47 Participants
|
66 Participants
|
|
Number of Participants With Maximum Grade 3-5 Toxicities
4
|
18 Participants
|
22 Participants
|
|
Number of Participants With Maximum Grade 3-5 Toxicities
5
|
9 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: 18 months post-transplantPopulation: Infection events
The number and types of infection events reported are tabulated.
Outcome measures
| Measure |
Reduced Intensity Conditioning (RIC)
n=283 Infection events
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Fludarabine and Busulfan: (Flu/Bu)
* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Fludarabine and Melphalan: (Flu/Mel)
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2
|
Myeloablative Conditioning Regimen (MAC)
n=353 Infection events
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Busulfan and Fludarabine: (Bu/Flu)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)
Busulfan and Cyclophosphamide: (Bu/Cy)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
|
|---|---|---|
|
Infection Type
Bacterial
|
161 Infection events
|
192 Infection events
|
|
Infection Type
Viral
|
95 Infection events
|
117 Infection events
|
|
Infection Type
Fungal
|
12 Infection events
|
37 Infection events
|
|
Infection Type
Protozoal
|
0 Infection events
|
1 Infection events
|
|
Infection Type
Other
|
15 Infection events
|
6 Infection events
|
SECONDARY outcome
Timeframe: 18 months post-transplantPopulation: Transplanted participants
The maximum severity of infections reported by participants are tabulated. The number of infections and the number of patients experiencing infections will be tabulated by type of infection, severity, and time period after transplant. The cumulative incidence of severe, life-threatening, or fatal infections will be compared between the two treatment arms at 6, 12, and 18 months from transplant or until death.
Outcome measures
| Measure |
Reduced Intensity Conditioning (RIC)
n=133 Participants
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Fludarabine and Busulfan: (Flu/Bu)
* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Fludarabine and Melphalan: (Flu/Mel)
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2
|
Myeloablative Conditioning Regimen (MAC)
n=132 Participants
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Busulfan and Fludarabine: (Bu/Flu)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)
Busulfan and Cyclophosphamide: (Bu/Cy)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
|
|---|---|---|
|
Number of Participants With Infections
None
|
43 Participants
|
38 Participants
|
|
Number of Participants With Infections
Moderate
|
37 Participants
|
42 Participants
|
|
Number of Participants With Infections
Severe
|
43 Participants
|
40 Participants
|
|
Number of Participants With Infections
Life Threatening or Fatal
|
10 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: 18 months post-randomizationPrimary cause of death was adjudicated using previously described criteria (Copelan et al. 2007). When relapse occurred, it was considered the primary cause of death regardless of other events.
Outcome measures
| Measure |
Reduced Intensity Conditioning (RIC)
n=137 Participants
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Fludarabine and Busulfan: (Flu/Bu)
* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Fludarabine and Melphalan: (Flu/Mel)
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2
|
Myeloablative Conditioning Regimen (MAC)
n=135 Participants
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Busulfan and Fludarabine: (Bu/Flu)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)
Busulfan and Cyclophosphamide: (Bu/Cy)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
|
|---|---|---|
|
Number of Participants With Cause of Death
Relapse
|
38 Participants
|
10 Participants
|
|
Number of Participants With Cause of Death
Organ failure
|
1 Participants
|
3 Participants
|
|
Number of Participants With Cause of Death
GVHD
|
4 Participants
|
15 Participants
|
|
Number of Participants With Cause of Death
Infection
|
0 Participants
|
2 Participants
|
|
Number of Participants With Cause of Death
Sudden death
|
1 Participants
|
0 Participants
|
|
Number of Participants With Cause of Death
Still alive
|
93 Participants
|
105 Participants
|
Adverse Events
Myeloablative Conditioning Regimen (MAC)
Serious events: 21 serious events
Other events: 7 other events
Deaths: 0 deaths
Reduced Intensity Conditioning (RIC)
Serious events: 16 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Myeloablative Conditioning Regimen (MAC)
n=132 participants at risk
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Busulfan and Fludarabine: (Bu/Flu)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)
Busulfan and Cyclophosphamide: (Bu/Cy)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
|
Reduced Intensity Conditioning (RIC)
n=133 participants at risk
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Fludarabine and Busulfan: (Flu/Bu)
* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Fludarabine and Melphalan: (Flu/Mel)
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2
|
|---|---|---|
|
Blood and lymphatic system disorders
Autoimmune haemolytic anaemia
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Blood and lymphatic system disorders
Immune thrombocytopenic purpura
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Cardiac disorders
Acute myocardial infarction
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Cardiac disorders
Atrial fibrillation
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/132 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Cardiac disorders
Pericardial effusion
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Eye disorders
Vision blurred
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/132 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/132 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Hepatobiliary disorders
Hepatic haemorrhage
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/132 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Immune system disorders
Graft versus host disease
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Infections and infestations
Device related infection
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Infections and infestations
Enterocolitis infectious
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Infections and infestations
Respiratory tract infection
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/132 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.00%
0/132 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
0.00%
0/132 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/132 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Investigations
Liver function test increased
|
0.00%
0/132 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/132 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/132 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
1.5%
2/133 • Number of events 2 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Nervous system disorders
Posterior reversible encephalopathy syndrome
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Nervous system disorders
Syncope
|
1.5%
2/132 • Number of events 2 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Nervous system disorders
Vocal cord paralysis
|
0.00%
0/132 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Psychiatric disorders
Mental status changes
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/132 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea at rest
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
3.0%
4/132 • Number of events 4 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/132 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.5%
2/132 • Number of events 2 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome
|
0.00%
0/132 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Surgical and medical procedures
Cholecystectomy
|
1.5%
2/132 • Number of events 2 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Surgical and medical procedures
Finger amputation
|
0.00%
0/132 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Surgical and medical procedures
Prostatectomy
|
0.00%
0/132 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Vascular disorders
Embolism
|
0.76%
1/132 • Number of events 2 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Vascular disorders
Hypotension
|
0.00%
0/132 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
1.5%
2/133 • Number of events 2 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Vascular disorders
Venoocclusive disease
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
Other adverse events
| Measure |
Myeloablative Conditioning Regimen (MAC)
n=132 participants at risk
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.
Busulfan and Fludarabine: (Bu/Flu)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m\^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -5 to -2
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2: Flu (total dose of 120 mg/m\^2)
Busulfan and Cyclophosphamide: (Bu/Cy)
* Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m\^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m\^2, respectively) on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
* TBI: 1200-1420 cGy on Days -7 to -4
* Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)
|
Reduced Intensity Conditioning (RIC)
n=133 participants at risk
One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.
Fludarabine and Busulfan: (Flu/Bu)
* Fludarabine: 30 mg/m\^2/day on Days -6 to -2 (total dose of 150 mg/m\^2)
* Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4
Fludarabine and Melphalan: (Flu/Mel)
* Fludarabine: 30 mg/m\^2/day on Days -5 to -2 (total dose of 120 mg/m\^2)
* Melphalan: 140 mg/m\^2 on Day -2
|
|---|---|---|
|
General disorders
Chest pain
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Investigations
Weight decreased
|
1.5%
2/132 • Number of events 2 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Large granular lymphocytosis
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Nervous system disorders
Syncope
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Psychiatric disorders
Mania
|
0.00%
0/132 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.76%
1/132 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.00%
0/133 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
|
Surgical and medical procedures
Hernia repair
|
0.00%
0/132 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
0.75%
1/133 • Number of events 1 • 18 months post-randomization
Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place