Trial Outcomes & Findings for TAC/MTX vs. TAC/MMF/PTCY for Prevention of Graft-versus-Host Disease and Microbiome and Immune Reconstitution Study (BMT CTN 1703/1801) (NCT NCT03959241)
NCT ID: NCT03959241
Last Updated: 2024-04-04
Results Overview
The primary endpoint is GRFS as a time to event endpoint from randomization. All randomized patients will be followed for one year; however, the primary endpoint will be analyzed as a time to event endpoint. The primary analysis will be done using the randomized population. An event for this time to event outcome is defined as grade III-IV acute GVHD, chronic GVHD requiring systemic immune suppression, disease relapse or progression, or death by any cause, whichever comes first. Time to event analyses were conducted. An unadjusted Kaplan-Meier analysis was done. Additionally, a multivariate Cox regression model adjusting for the following pre-specified covariates: age group (\< 65 vs. 65+), disease risk index (low, intermediate, high/very high), planned RIC conditioning regimen (Fludarabine/Busulfan, Fludarabine/Melphalan, Other), donor type/HLA matching score (related 6/6, unrelated 7/8, unrelated 8/8), and planned use of post-transplant maintenance therapy (Yes vs. no).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
431 participants
Primary outcome timeframe
1 year post randomization
Results posted on
2024-04-04
Participant Flow
BMT CTN 1703's enrollment was between June 2019 and June 2021 with 431 participants enrolled from 37 centers. The study opened to accrual on June 25, 2019 with 39 centers activated for enrollment. The study closed to accrual on June 18, 2021 and study completed on September 19, 2022. BMT CTN 1801 is a companion study to BMT CTN 1703. The accrual goal was 300 participants. Enrollment to BMT CTN 1801 is performed solely through co-enrollment of BMT CTN 1703 participants.
Enrolled participants were randomized in a 1:1 ratio to the two treatment arms. This is an open-label study and not blinded in treatment assignment. The randomized participants were intended to undergo transplant. For various reasons, a small portion of participants did not receive a transplant.
Participant milestones
| Measure |
PTCY/Tacrolimus/MMF
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Overall Study
STARTED
|
214
|
217
|
|
Overall Study
COMPLETED
|
203
|
208
|
|
Overall Study
NOT COMPLETED
|
11
|
9
|
Reasons for withdrawal
| Measure |
PTCY/Tacrolimus/MMF
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
7
|
8
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Move to Hospice Care
|
1
|
0
|
|
Overall Study
Screen Failure
|
1
|
0
|
|
Overall Study
Disease Relapse
|
0
|
1
|
|
Overall Study
Off Study
|
1
|
0
|
Baseline Characteristics
TAC/MTX vs. TAC/MMF/PTCY for Prevention of Graft-versus-Host Disease and Microbiome and Immune Reconstitution Study (BMT CTN 1703/1801)
Baseline characteristics by cohort
| Measure |
PTCY/Tacrolimus/MMF
n=214 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=217 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
Total
n=431 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64.2 years
STANDARD_DEVIATION 8.5 • n=5 Participants
|
64.5 years
STANDARD_DEVIATION 8.9 • n=7 Participants
|
64.3 years
STANDARD_DEVIATION 8.7 • n=5 Participants
|
|
Age, Customized
18-64 years
|
94 Participants
n=5 Participants
|
92 Participants
n=7 Participants
|
186 Participants
n=5 Participants
|
|
Age, Customized
65 years or older
|
120 Participants
n=5 Participants
|
125 Participants
n=7 Participants
|
245 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
80 Participants
n=5 Participants
|
91 Participants
n=7 Participants
|
171 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
134 Participants
n=5 Participants
|
126 Participants
n=7 Participants
|
260 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
9 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
203 Participants
n=5 Participants
|
191 Participants
n=7 Participants
|
394 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
10 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
186 Participants
n=5 Participants
|
193 Participants
n=7 Participants
|
379 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
10 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Karnofsky / Lansky Performance Score
At least 90
|
106 Participants
n=5 Participants
|
108 Participants
n=7 Participants
|
214 Participants
n=5 Participants
|
|
Karnofsky / Lansky Performance Score
Less Than 90
|
108 Participants
n=5 Participants
|
109 Participants
n=7 Participants
|
217 Participants
n=5 Participants
|
|
Primary Disease
Acute lymphoblastic leukemia (ALL)
|
12 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Primary Disease
Acute myelogenous leukemia (AML)
|
107 Participants
n=5 Participants
|
100 Participants
n=7 Participants
|
207 Participants
n=5 Participants
|
|
Primary Disease
Chronic myelogenous leukemia (CML)
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Primary Disease
Myelodysplastic syndrome (MDS)
|
63 Participants
n=5 Participants
|
65 Participants
n=7 Participants
|
128 Participants
n=5 Participants
|
|
Primary Disease
Hodgkin lymphoma
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Primary Disease
Mantle cell lymphoma
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Primary Disease
Indolent NHL
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Primary Disease
T-cell NHL
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Primary Disease
Aggressive NHL
|
9 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Primary Disease
Burkitt lymphoma
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Primary Disease
Biphenotypic leukemia
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Time from Disease Diagnosis to Transplant
|
12.3 months
STANDARD_DEVIATION 17.0 • n=5 Participants
|
13.1 months
STANDARD_DEVIATION 21.5 • n=7 Participants
|
12.7 months
STANDARD_DEVIATION 19.4 • n=5 Participants
|
|
Disease Risk Index
Low
|
19 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Disease Risk Index
Intermediate
|
125 Participants
n=5 Participants
|
125 Participants
n=7 Participants
|
250 Participants
n=5 Participants
|
|
Disease Risk Index
High / Very High
|
70 Participants
n=5 Participants
|
71 Participants
n=7 Participants
|
141 Participants
n=5 Participants
|
|
Allogeneic Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) total score
0
|
49 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
102 Participants
n=5 Participants
|
|
Allogeneic Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) total score
1
|
31 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
65 Participants
n=5 Participants
|
|
Allogeneic Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) total score
2
|
60 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
94 Participants
n=5 Participants
|
|
Allogeneic Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) total score
3
|
24 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
57 Participants
n=5 Participants
|
|
Allogeneic Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) total score
4+
|
40 Participants
n=5 Participants
|
55 Participants
n=7 Participants
|
95 Participants
n=5 Participants
|
|
Allogeneic Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) total score
Missing/Unknown
|
10 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Donor Type and HLA Matching
Related donor 6/6
|
60 Participants
n=5 Participants
|
68 Participants
n=7 Participants
|
128 Participants
n=5 Participants
|
|
Donor Type and HLA Matching
Unrelated donor 7/8
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Donor Type and HLA Matching
Unrelated donor 8/8
|
147 Participants
n=5 Participants
|
141 Participants
n=7 Participants
|
288 Participants
n=5 Participants
|
|
Donor/Recipient CMV Status
Pos/Pos
|
61 Participants
n=5 Participants
|
71 Participants
n=7 Participants
|
132 Participants
n=5 Participants
|
|
Donor/Recipient CMV Status
Pos/Neg
|
20 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Donor/Recipient CMV Status
Neg/Pos
|
67 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
107 Participants
n=5 Participants
|
|
Donor/Recipient CMV Status
Neg/Neg
|
59 Participants
n=5 Participants
|
70 Participants
n=7 Participants
|
129 Participants
n=5 Participants
|
|
Donor/Recipient CMV Status
Missing/Unknown
|
7 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Donor/Recipient Sex Match
M-M
|
85 Participants
n=5 Participants
|
75 Participants
n=7 Participants
|
160 Participants
n=5 Participants
|
|
Donor/Recipient Sex Match
M-F
|
41 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
95 Participants
n=5 Participants
|
|
Donor/Recipient Sex Match
F-M
|
47 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
96 Participants
n=5 Participants
|
|
Donor/Recipient Sex Match
F-F
|
36 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
71 Participants
n=5 Participants
|
|
Donor/Recipient Sex Match
Missing/Unknown
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Donor/Recipient ABO Match
Match
|
122 Participants
n=5 Participants
|
111 Participants
n=7 Participants
|
233 Participants
n=5 Participants
|
|
Donor/Recipient ABO Match
Minor Mismatch
|
6 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Donor/Recipient ABO Match
Major Mismatch
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Donor/Recipient ABO Match
Bidirectional Mismatch
|
66 Participants
n=5 Participants
|
83 Participants
n=7 Participants
|
149 Participants
n=5 Participants
|
|
Donor/Recipient ABO Match
Missing/Unknown
|
18 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Received reduced intensity conditioning regimen
Fludarabine/Busulfan
|
56 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
117 Participants
n=5 Participants
|
|
Received reduced intensity conditioning regimen
Fludarabine/Melphalan
|
122 Participants
n=5 Participants
|
123 Participants
n=7 Participants
|
245 Participants
n=5 Participants
|
|
Received reduced intensity conditioning regimen
Fludarabine/Cyclophosphamide
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Received reduced intensity conditioning regimen
Fludarabine/TBI
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Received reduced intensity conditioning regimen
Fludarabine/Cyclophosphamide/TBI
|
24 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
|
Received reduced intensity conditioning regimen
Missing/Unknown
|
6 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Planned Reduced Intensity Conditioning Regimen
Fludarabine/Busulfan
|
58 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
119 Participants
n=5 Participants
|
|
Planned Reduced Intensity Conditioning Regimen
Fludarabine/Melphalan
|
125 Participants
n=5 Participants
|
127 Participants
n=7 Participants
|
252 Participants
n=5 Participants
|
|
Planned Reduced Intensity Conditioning Regimen
Fludarabine/Cyclophosphamide
|
6 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Planned Reduced Intensity Conditioning Regimen
Fludarabine/TBI
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Planned Reduced Intensity Conditioning Regimen
Fludarabine/Cyclophosphamide/TBI
|
24 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
|
Planned Post-Transplant Maintenance Therapy
No Planned Post-Transplant Maintenance Therapy
|
159 Participants
n=5 Participants
|
170 Participants
n=7 Participants
|
329 Participants
n=5 Participants
|
|
Planned Post-Transplant Maintenance Therapy
Tyrosine Kinase Inhibitor
|
12 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Planned Post-Transplant Maintenance Therapy
FLT3 Inhibitor
|
10 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Planned Post-Transplant Maintenance Therapy
Monoclonal Antibody
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Planned Post-Transplant Maintenance Therapy
Clinical Trial
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Planned Post-Transplant Maintenance Therapy
Other
|
31 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 year post randomizationPopulation: Analysis Population includes all randomized participants
The primary endpoint is GRFS as a time to event endpoint from randomization. All randomized patients will be followed for one year; however, the primary endpoint will be analyzed as a time to event endpoint. The primary analysis will be done using the randomized population. An event for this time to event outcome is defined as grade III-IV acute GVHD, chronic GVHD requiring systemic immune suppression, disease relapse or progression, or death by any cause, whichever comes first. Time to event analyses were conducted. An unadjusted Kaplan-Meier analysis was done. Additionally, a multivariate Cox regression model adjusting for the following pre-specified covariates: age group (\< 65 vs. 65+), disease risk index (low, intermediate, high/very high), planned RIC conditioning regimen (Fludarabine/Busulfan, Fludarabine/Melphalan, Other), donor type/HLA matching score (related 6/6, unrelated 7/8, unrelated 8/8), and planned use of post-transplant maintenance therapy (Yes vs. no).
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=214 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=217 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Percentage of Participants With GVHD/Relapse or Progression-free Survival (GRFS) at One Year
|
52.3 percentage of participants
Interval 45.2 to 58.8
|
35.5 percentage of participants
Interval 29.1 to 42.0
|
SECONDARY outcome
Timeframe: Days 100 post-transplantPopulation: Analysis Population includes transplanted participants.
Acute GVHD was graded according to Mount Sinai aGVHD International Consortium (MAGIC) Criteria (Harris et al. 2016) with higher grade indicating worse outcomes. Grade I aGVHD is defined as Skin stage 1-2 and stage 0 for both GI and liver. Grade II is stage 3 skin, stage 1 GI, or stage 1 liver. Grade III is stage 2-3 GI or stage 2-3 liver. Grade IV is stage 4 skin or stage 4 liver. The cumulative incidence of acute GVHD grade II-IV and III-IV at Day 100 was estimated using the Aalen-Johansen estimator with 95% confidence intervals, treating death prior to aGVHD as a competing event. The cumulative incidences of Minnesota standard and high risk aGVHD at Day 100 were determined with 95% confidence intervals. Time to aGVHD is defined as time from transplant until onset of grades II-IV and III-IV aGVHD, respectively. A multivariate Cox regression model was used to compare the treatment groups, with adjustment for same baseline characteristics as for the primary endpoint.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Percentage of Participants With Grades II-IV and III-IV Acute GVHD at Day 100 Post-transplant
MAGIC aGVHD Grade II-IV
|
53.8 percentage of participants
Interval 46.7 to 60.4
|
51.9 percentage of participants
Interval 44.9 to 58.4
|
|
Percentage of Participants With Grades II-IV and III-IV Acute GVHD at Day 100 Post-transplant
MAGIC aGVHD Grade III-IV
|
6.3 percentage of participants
Interval 3.5 to 10.2
|
14.7 percentage of participants
Interval 10.3 to 19.8
|
|
Percentage of Participants With Grades II-IV and III-IV Acute GVHD at Day 100 Post-transplant
Standard risk aGVHD
|
64.1 percentage of participants
Interval 57.1 to 70.3
|
64.3 percentage of participants
Interval 57.4 to 70.4
|
|
Percentage of Participants With Grades II-IV and III-IV Acute GVHD at Day 100 Post-transplant
High risk aGVHD
|
13.1 percentage of participants
Interval 8.9 to 18.1
|
18.5 percentage of participants
Interval 13.6 to 24.0
|
SECONDARY outcome
Timeframe: One year post-transplantPopulation: Analysis Population includes transplanted participants
Acute GVHD were graded according to Mount Sinai Acute GVHD International Consortium (MAGIC) Criteria (Harris et al. Biology of Blood and Marrow Transplantation 2016; 22:4-10). The higher acute GVHD grade indicates worse outcomes. Grade 0 is no acute GVHD of any organ. Grade I acute GVHD is defined as Skin stage of 1-2 and stage 0 for both GI and liver organs. Grade II is stage 3 of skin, or stage 1 of GI, or stage 1 of liver. Grade III is stage 2-3 for GI, or stage 2-3 of liver. Grade IV is stage 4 of skin, or stage 4 of liver. Max acute GVHD by one-year post-transplant was computed.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Participants With Maximum Acute GVHD at One Year Post-transplant
Grade 0
|
66 Participants
|
60 Participants
|
|
Participants With Maximum Acute GVHD at One Year Post-transplant
Grade I
|
27 Participants
|
32 Participants
|
|
Participants With Maximum Acute GVHD at One Year Post-transplant
Grade II
|
99 Participants
|
81 Participants
|
|
Participants With Maximum Acute GVHD at One Year Post-transplant
Grade III
|
11 Participants
|
25 Participants
|
|
Participants With Maximum Acute GVHD at One Year Post-transplant
Grade IV
|
5 Participants
|
14 Participants
|
SECONDARY outcome
Timeframe: Day 100 post-transplantPopulation: Analysis Population includes transplanted participants
Organ stages were graded according to Mount Sinai Acute GVHD International Consortium (MAGIC) Criteria (Harris et al. 2016). Higher stage in any organ indicates worse outcomes. For skin, stage 0-no GVHD rash; 1-Maculopapular Rash \<25% BSA; 2-Maculopapular Rash 25-50% BSA; 3-Maculopapular Rash \>50% BSA; 4-Generalized Erythroderma Plus Bullous Formation and Desquamation \>5% BSA. For Lower GI, 0-No Diarrhea or Diarrhea-Adult: \<500 mL/day, \<3 Episodes/day; Child: \<10 mL/kg/day, \<4 Episodes/day; 1-Diarrhea-Adult: 500-999 mL/day, 3-4 Episodes/day; Child: 10-19.9 mL/kg/day, 4-6 Episodes/day; 2-Diarrhea-Adult: 1000-1500 mL/day, 5-7 Episodes/day; Child: 20-30 mL/kg/day, 7-10 Episodes/day; 3-Diarrhea-Adult: \>1500 mL/day, \>7 Episodes/day; Child: \>30 mL/kg/day, \>10 Episodes/day; 4-Severe Abdominal Pain With or Without Ileus or Grossly Bloody Stool. For liver, 0-Bilirubin \<2.0 mg/dL; 1-Bilirubin 2.0-3.0 mg/dL; 2-Bilirubin 3.1-6.0 mg/dL; 3-Bilirubin 6.1-15.0 mg/dL; 4-Bilirubin \>15.0 mg/dL
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Participants With Maximum Stage of Skin, Lower GI, and Liver at Day 100 Post-transplant
Skin · 0
|
121 Participants
|
125 Participants
|
|
Participants With Maximum Stage of Skin, Lower GI, and Liver at Day 100 Post-transplant
Skin · 1
|
54 Participants
|
40 Participants
|
|
Participants With Maximum Stage of Skin, Lower GI, and Liver at Day 100 Post-transplant
Skin · 2
|
16 Participants
|
18 Participants
|
|
Participants With Maximum Stage of Skin, Lower GI, and Liver at Day 100 Post-transplant
Skin · 3
|
14 Participants
|
21 Participants
|
|
Participants With Maximum Stage of Skin, Lower GI, and Liver at Day 100 Post-transplant
Skin · 4
|
3 Participants
|
8 Participants
|
|
Participants With Maximum Stage of Skin, Lower GI, and Liver at Day 100 Post-transplant
Lower GI · 0
|
155 Participants
|
159 Participants
|
|
Participants With Maximum Stage of Skin, Lower GI, and Liver at Day 100 Post-transplant
Lower GI · 1
|
33 Participants
|
27 Participants
|
|
Participants With Maximum Stage of Skin, Lower GI, and Liver at Day 100 Post-transplant
Lower GI · 2
|
9 Participants
|
11 Participants
|
|
Participants With Maximum Stage of Skin, Lower GI, and Liver at Day 100 Post-transplant
Lower GI · 3
|
10 Participants
|
11 Participants
|
|
Participants With Maximum Stage of Skin, Lower GI, and Liver at Day 100 Post-transplant
Lower GI · 4
|
1 Participants
|
4 Participants
|
|
Participants With Maximum Stage of Skin, Lower GI, and Liver at Day 100 Post-transplant
Liver · 0
|
198 Participants
|
192 Participants
|
|
Participants With Maximum Stage of Skin, Lower GI, and Liver at Day 100 Post-transplant
Liver · 1
|
9 Participants
|
7 Participants
|
|
Participants With Maximum Stage of Skin, Lower GI, and Liver at Day 100 Post-transplant
Liver · 2
|
0 Participants
|
8 Participants
|
|
Participants With Maximum Stage of Skin, Lower GI, and Liver at Day 100 Post-transplant
Liver · 3
|
1 Participants
|
5 Participants
|
|
Participants With Maximum Stage of Skin, Lower GI, and Liver at Day 100 Post-transplant
Liver · 4
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 100 post-transplantPopulation: Analysis Population includes transplanted participants
Organ stages were graded according to Mount Sinai Acute GVHD International Consortium (MAGIC) Criteria (Harris et al. 2016). Higher stage in any organ indicates worse outcomes. For upper GI, stage 0 is no or intermittent nausea, vomiting, or anorexia; stage 1 is persistent nausea, vomiting, or anorexia. The maximum stages of Upper GI at patient level were summarized at Day 100.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Participants With Maximum Stage of Upper GI at Day 100 Post-transplant
0
|
136 Participants
|
137 Participants
|
|
Participants With Maximum Stage of Upper GI at Day 100 Post-transplant
1
|
72 Participants
|
75 Participants
|
SECONDARY outcome
Timeframe: 6, 12 months post-transplantPopulation: Analysis Population includes transplanted participants
Percentage of participants with chronic GVHD (cGVHD) at one-year will be estimated with 95% confidence intervals for each treatment group using the cumulative incidence estimate with the complementary log-log transformation, treating death prior to cGVHD as a competing event. Chronic GVHD is based on NIH Consensus Criteria (2014 NIH Consensus Criteria) and includes mild, moderate and severe chronic GVHD. Eight organs were scored on a 0-3 scale to reflect degree of cGVHD involvement. Liver and pulmonary function test results and use of systemic therapy for treatment of cGVHD were also recorded. Assessment of cGVHD occurred up to one-year post-transplant. This endpoint considers any cGVHD onset. A multivariate Cox regression model for the cause-specific hazard of cGVHD was used to compare the treatment groups, after adjustment for baseline characteristics as described for the primary endpoint.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Percentage of Participants With Chronic GVHD Post-transplant
6 months post transplant
|
11.3 percentage of participants
Interval 7.4 to 16.1
|
13.9 percentage of participants
Interval 9.6 to 19.0
|
|
Percentage of Participants With Chronic GVHD Post-transplant
12 months post transplant
|
21.9 percentage of participants
Interval 16.4 to 27.9
|
35.1 percentage of participants
Interval 28.7 to 41.6
|
SECONDARY outcome
Timeframe: 12 months post-transplantPopulation: Analysis Population includes transplanted participants
Chronic GVHD data were collected directly from providers and chart review as defined by the NIH Consensus Conference Criteria. Eight organs were scored on a 0-3 scale to reflect degree of chronic GVHD involvement per the NIH global severity scores of mild, moderate and severe chronic GVHD. The maximum severity of chronic GVHD through 12 months post-transplant will be tabulated by treatment arm.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Number of Participants Experiencing Chronic GVHD With Maximum Severity at 12 Months Post-transplant
None
|
164 Participants
|
139 Participants
|
|
Number of Participants Experiencing Chronic GVHD With Maximum Severity at 12 Months Post-transplant
Mild
|
29 Participants
|
36 Participants
|
|
Number of Participants Experiencing Chronic GVHD With Maximum Severity at 12 Months Post-transplant
Moderate
|
11 Participants
|
24 Participants
|
|
Number of Participants Experiencing Chronic GVHD With Maximum Severity at 12 Months Post-transplant
Severe
|
3 Participants
|
11 Participants
|
|
Number of Participants Experiencing Chronic GVHD With Maximum Severity at 12 Months Post-transplant
Unknown
|
1 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: 1 year post-transplantPopulation: Analysis Population includes transplanted and evaluable participants for ISFS
Participants who are alive, relapse-free, and do not need ongoing immune suppression (IS) to control GVHD at one year post-transplant are considered successes for the endpoint immunosuppression-free survival (ISFS). Immune suppression is defined as any systemic agents used to control or suppress GVHD. Corticosteroid doses greater than 10 mg were considered active systemic immune suppression treatment. Participants who discontinued immune suppression within 15 days or less prior to the 1-year time point was considered to be on immune suppression for this endpoint.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=198 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=204 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Number of Participants With Immunosuppression-Free Survival (ISFS) at 1 Year Post-transplant
Alive & Relapse
|
21 Participants
|
22 Participants
|
|
Number of Participants With Immunosuppression-Free Survival (ISFS) at 1 Year Post-transplant
Immunosuppression-Free Survival
|
99 Participants
|
81 Participants
|
|
Number of Participants With Immunosuppression-Free Survival (ISFS) at 1 Year Post-transplant
Death
|
46 Participants
|
56 Participants
|
|
Number of Participants With Immunosuppression-Free Survival (ISFS) at 1 Year Post-transplant
Alive, no relapse, and still on IS
|
32 Participants
|
45 Participants
|
SECONDARY outcome
Timeframe: 1 year post-transplantPopulation: Analysis Population includes transplanted and evaluable participants for ISFS.
Participants who are alive, relapse-free, and do not need ongoing immune suppression to control GVHD at one year post-transplant are considered successes for the endpoint immunosuppression-free survival (ISFS). Percentage of participants alive, relapse free, and off immune suppression at 1 year post-transplant were described for each treatment group, along with 95% Clopper-Pearson confidence intervals.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Percentage of Participants With Immunosuppression-Free Survival (ISFS) at 1 Year Post-transplant
|
50 percentage of participants
Interval 42.8 to 57.2
|
39.7 percentage of participants
Interval 32.9 to 42.8
|
SECONDARY outcome
Timeframe: Days 28 and day 100 post-transplantPopulation: Analysis Population includes transplanted participants
Neutrophil recovery is defined as achieving an absolute neutrophil count (ANC) greater than or equal to 500/mm\^3 for three consecutive measurements on three different days. The first of the three days will be designated the day of neutrophil recovery. The competing event is death without neutrophil recovery. For participants who never drop ANC below 500/mm\^3, the date of neutrophil recovery will be Day +1 post-transplant. The cumulative incidence of neutrophil recovery by Day 28 and Day 100 was described for each treatment group with point estimates and 95% confidence intervals using the complementary log-log transformation and treating death as a competing event.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Percentage of Participants With Neutrophil Recovery Post-transplant
Day 28 post-transplant
|
90.3 percentage of participants
Interval 85.3 to 93.6
|
93.4 percentage of participants
Interval 89.0 to 96.1
|
|
Percentage of Participants With Neutrophil Recovery Post-transplant
Day 100 post-transplant
|
92.7 percentage of participants
Interval 88.1 to 95.6
|
97.2 percentage of participants
Interval 93.6 to 98.8
|
SECONDARY outcome
Timeframe: Day 60 and Day 100 post-transplantPopulation: Analysis Population includes transplanted participants with platelet recovery data provided
Platelet recovery is defined by two different metrics: the first day of a sustained platelet count greater than or equal to 20,000/mm\^3 or greater than or equal to 50,000/mm\^3 with no platelet transfusions in the preceding seven days. The first day of sustained platelet count above these thresholds will be designated the day of platelet engraftment. For participants who never drop their platelet count below 20,000/mm\^3 or 50,000/mm\^3, the date of platelet recovery will be Day +1 post HCT. The competing event is death without platelet recovery. The cumulative incidence estimate of platelet recovery by Day 60 and Day 100 were described by treatment group with 95% confidence intervals (complementary log-log transformation), treating death as a competing event.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Percentage of Participants With Platelet Recovery Post-transplant
Day 60 post-transplant of Platelet Recovery to >20k
|
88.3 percentage of participants
Interval 83.0 to 92.0
|
91.8 percentage of participants
Interval 87.1 to 94.8
|
|
Percentage of Participants With Platelet Recovery Post-transplant
Day 100 post-transplant of Platelet Recovery to >20k
|
90.3 percentage of participants
Interval 85.3 to 93.7
|
92.8 percentage of participants
Interval 88.2 to 95.6
|
|
Percentage of Participants With Platelet Recovery Post-transplant
Day 60 post-transplant of Platelet Recovery to >50k
|
77.6 percentage of participants
Interval 71.2 to 82.7
|
82.7 percentage of participants
Interval 76.8 to 87.2
|
|
Percentage of Participants With Platelet Recovery Post-transplant
Day 100 post-transplant of Platelet Recovery to >50k
|
79.5 percentage of participants
Interval 73.3 to 84.4
|
83.7 percentage of participants
Interval 77.9 to 88.1
|
SECONDARY outcome
Timeframe: Day 60, Day 100, 6 Months, and 1 year post-transplantPopulation: Analysis Population includes transplanted participants with lymphocyte recovery data provided.
Lymphocyte recovery is defined as the first day of sustained absolute lymphocyte count greater than or equal to 1000/mm\^3. The competing event is death without lymphocyte recovery. The cumulative incidence estimate of Lymphocyte recovery were described by treatment group with 95% confidence intervals (complementary log-log transformation), treating death as a competing event.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Percentage of Participants With Lymphocyte Recovery Post-transplant
Day 60 post-transplant
|
29.6 percentage of participants
Interval 23.5 to 35.9
|
48.2 percentage of participants
Interval 41.3 to 54.8
|
|
Percentage of Participants With Lymphocyte Recovery Post-transplant
Day 100 post-transplant
|
32.5 percentage of participants
Interval 26.2 to 39.0
|
52.5 percentage of participants
Interval 45.5 to 59.0
|
|
Percentage of Participants With Lymphocyte Recovery Post-transplant
6 Months post-transplant
|
41.5 percentage of participants
Interval 34.7 to 48.2
|
58.3 percentage of participants
Interval 51.3 to 64.6
|
|
Percentage of Participants With Lymphocyte Recovery Post-transplant
1 Year post-transplant
|
47.1 percentage of participants
Interval 40.1 to 53.8
|
63.2 percentage of participants
Interval 56.2 to 69.4
|
SECONDARY outcome
Timeframe: Day 28 and Day 100 post-transplantPopulation: Analysis Population includes transplanted participants.
Donor cell engraftment were assessed with donor/recipient chimerism studies. Mixed chimerism is defined as the presence of donor cells, as a proportion of total cells to be less than 95% but at least 5% in the bone marrow or peripheral blood. Full donor chimerism is defined as greater than or equal to 95% of donor cells. Mixed and full chimerism will be evidence of donor cell engraftment. Donor cells of less than 5% will be considered as graft rejection. The number of participants with each level of chimerism described above is described as part of this outcome.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Number of Participants With Each Level of Donor Cell Engraftment Post-transplant
Day 28 post-transplant · Full (>95% Donor Cells)
|
126 Participants
|
129 Participants
|
|
Number of Participants With Each Level of Donor Cell Engraftment Post-transplant
Day 28 post-transplant · Mixed (5-95% Donor Cells)
|
39 Participants
|
45 Participants
|
|
Number of Participants With Each Level of Donor Cell Engraftment Post-transplant
Day 28 post-transplant · Graft Rejection (<5% Donor Cells)
|
4 Participants
|
4 Participants
|
|
Number of Participants With Each Level of Donor Cell Engraftment Post-transplant
Day 28 post-transplant · Data missing
|
39 Participants
|
34 Participants
|
|
Number of Participants With Each Level of Donor Cell Engraftment Post-transplant
Day 100 post-transplant · Full (>95% Donor Cells)
|
116 Participants
|
124 Participants
|
|
Number of Participants With Each Level of Donor Cell Engraftment Post-transplant
Day 100 post-transplant · Mixed (5-95% Donor Cells)
|
48 Participants
|
58 Participants
|
|
Number of Participants With Each Level of Donor Cell Engraftment Post-transplant
Day 100 post-transplant · Graft Rejection (<5% Donor Cells)
|
5 Participants
|
1 Participants
|
|
Number of Participants With Each Level of Donor Cell Engraftment Post-transplant
Day 100 post-transplant · Data missing
|
39 Participants
|
29 Participants
|
SECONDARY outcome
Timeframe: Day 28 and Day 100 post-transplantPopulation: Analysis Population includes transplanted participants who submitted post-transplant assessments.
Donor cell engraftment were assessed with donor/recipient chimerism studies. Mixed chimerism is defined as the presence of donor cells, as a percentage of total cells to be less than 95% but at least 5% in the bone marrow or peripheral blood. Full donor chimerism is defined as greater than or equal to 95% of donor cells. Mixed and full chimerism will be evidence of donor cell engraftment. Donor cells of less than 5% will be considered as graft rejection. Donor chimerism at Day 28 and Day 100 after transplant in each of the randomized treatment arms will be described numerically as median and range for those evaluable.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Summary Statistics for Donor Chimerism
Day 28 post-transplant
|
100 percentage of donor cells
Interval 0.0 to 100.0
|
100 percentage of donor cells
Interval 0.0 to 100.0
|
|
Summary Statistics for Donor Chimerism
Day 100 post-transplant
|
99 percentage of donor cells
Interval 0.0 to 100.0
|
99 percentage of donor cells
Interval 4.0 to 100.0
|
SECONDARY outcome
Timeframe: 1 year post-transplantPopulation: Analysis Population includes transplanted participants
Disease relapse/progression is defined as being alive and free of relapse/progression of the primary disease. The time from transplant until relapse/progression of the primary disease, or cumulative incidence, was estimated at one-year post-transplant along with 95% CIs computed using the complementary log-log transformation, treating death prior to disease relapse as a competing event. A multivariate Cox regression model for the cause-specific hazard of relapse or progression will be used to compare the treatment groups, after adjustment for baseline characteristics as described for the primary endpoint.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Percentage of Participants With Disease Relapse at 1 Year Post-transplant
|
20.8 percentage of participants
Interval 15.5 to 26.7
|
20.2 percentage of participants
Interval 15.0 to 25.9
|
SECONDARY outcome
Timeframe: Days 100, 180 and 1 year post-transplantPopulation: Analysis Population includes transplanted participants
An event for this endpoint TRM is death without evidence of disease progression or recurrence. Disease progression or recurrence will be considered a competing event. The time from transplant until TRM, or cumulative incidence, estimated at specific time points along with 95% CIs computed using the complementary log-log transformation, treating relapse/progression of the primary disease as a competing risk. A multivariate Cox regression model for the cause-specific hazard of TRM was used to compare the treatment groups, after adjustment for baseline characteristics as described for the primary endpoint.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Percentage of Participants With Treatment-related Mortality (TRM) Post-transplant
Day 100 post-transplant
|
6.8 percentage of participants
Interval 3.9 to 10.8
|
7.6 percentage of participants
Interval 4.5 to 11.7
|
|
Percentage of Participants With Treatment-related Mortality (TRM) Post-transplant
Day 180 post-transplant
|
8.8 percentage of participants
Interval 5.4 to 13.2
|
13.3 percentage of participants
Interval 9.1 to 18.3
|
|
Percentage of Participants With Treatment-related Mortality (TRM) Post-transplant
12 Months post-transplant
|
12.3 percentage of participants
Interval 8.2 to 17.2
|
17.2 percentage of participants
Interval 12.4 to 22.6
|
SECONDARY outcome
Timeframe: 1 year post-transplantPopulation: Analysis Population includes transplanted participants
All Grade 3-5 toxicities will be tabulated by grade for each randomized treatment arm, by type of toxicity as well as the peak grade overall. Toxicities were evaluated using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Grades 3-5 General Disorders
|
51 Participants
|
48 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Grades 3-5 Immune System Disorders
|
5 Participants
|
6 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Grades 3-5 GI Disorders
|
57 Participants
|
77 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Grades 3-5 Renal Disorders
|
33 Participants
|
30 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Grades 3-5 Hemorrhagic Disorders
|
12 Participants
|
11 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Grades 3-5 Cardiac Disorders
|
71 Participants
|
72 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Grades 3-5 Nervous System Disorders
|
12 Participants
|
20 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Grades 3-5 Blood and Lymphatic Disorders
|
3 Participants
|
3 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Grades 3-5 Vascular Disorders
|
6 Participants
|
12 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Grades 3-5 Musculoskeletal and Connective Tissue Disorders
|
17 Participants
|
12 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Grades 3-5 Respiratory, Thoracic and Mediastinal Disorders
|
41 Participants
|
42 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Grades 3-5 Metabolism and Nutrition Disorders
|
24 Participants
|
33 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Grades 3-5 Hepatic Disorders
|
24 Participants
|
44 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Received Dialysis
|
11 Participants
|
8 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Hepatitis
|
6 Participants
|
4 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Liver failure
|
2 Participants
|
4 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Abnormal liver function
|
14 Participants
|
15 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Overall Grade 3
|
141 Participants
|
146 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Overall Grade 4
|
23 Participants
|
27 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Overall Grade 5
|
12 Participants
|
11 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Maximum Toxicity Grade 3
|
113 Participants
|
116 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Maximum Toxicity Grade 4
|
17 Participants
|
22 Participants
|
|
Number of Participants Reporting Grade 3-5 Toxicities by 1 Year Post-transplant
Maximum Toxicity Grade 5
|
12 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: 1 year post-transplantPopulation: Analysis Population includes transplanted participants
All Grade 2 and 3 infections were reported according to the BMT CTN Technical Manual of Procedures (MOP) up to 1 year post-transplant. The frequency of Grade 2-3 infections and the number of participants experiencing infections occurring within 1 year post-transplant, are tabulated by treatment arm, organism, time period of infection onset, and severity, with Grade defined per the BMT CTN Technical MOP.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Frequencies of Infections Categorized by Infection Type
Bacterial
|
128 infections
|
118 infections
|
|
Frequencies of Infections Categorized by Infection Type
Viral
|
70 infections
|
61 infections
|
|
Frequencies of Infections Categorized by Infection Type
Fungal
|
18 infections
|
14 infections
|
|
Frequencies of Infections Categorized by Infection Type
Protozoal/Parasite
|
0 infections
|
0 infections
|
|
Frequencies of Infections Categorized by Infection Type
Other
|
34 infections
|
46 infections
|
SECONDARY outcome
Timeframe: 1 year post-transplantPopulation: Analysis Population includes transplanted participants
All Grade 2 and 3 infections were reported according to the BMT CTN Technical Manual of Procedures (MOP) up to 1 year post-transplant. The frequency of Grade 2-3 infections and the number of participants experiencing infections occurring within 1 year post-transplant, are tabulated by treatment arm, organism, time period of infection onset, and severity, with Grade defined per the BMT CTN Technical MOP.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Number of Participants With Grade 2 and 3 Infections
Patients with Infections
|
109 Participants
|
100 Participants
|
|
Number of Participants With Grade 2 and 3 Infections
Patients with 1 Infection
|
46 Participants
|
46 Participants
|
|
Number of Participants With Grade 2 and 3 Infections
Patients with 2 Infections
|
32 Participants
|
24 Participants
|
|
Number of Participants With Grade 2 and 3 Infections
Patients with 3 Infections
|
14 Participants
|
10 Participants
|
|
Number of Participants With Grade 2 and 3 Infections
Patients with 4 Infections
|
8 Participants
|
7 Participants
|
|
Number of Participants With Grade 2 and 3 Infections
Patients with 5 Infections
|
4 Participants
|
5 Participants
|
|
Number of Participants With Grade 2 and 3 Infections
Patients with >= 6 Infections
|
5 Participants
|
8 Participants
|
|
Number of Participants With Grade 2 and 3 Infections
Maximum Severity of None
|
99 Participants
|
112 Participants
|
|
Number of Participants With Grade 2 and 3 Infections
Maximum Severity of Grade 1
|
21 Participants
|
19 Participants
|
|
Number of Participants With Grade 2 and 3 Infections
Maximum Severity of Grade 2
|
57 Participants
|
36 Participants
|
|
Number of Participants With Grade 2 and 3 Infections
Maximum Severity of Grade 3
|
25 Participants
|
28 Participants
|
|
Number of Participants With Grade 2 and 3 Infections
CMV Reactivation by Day 100
|
15 Participants
|
16 Participants
|
|
Number of Participants With Grade 2 and 3 Infections
Non-Microbial Infections
|
9 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: 6 months and 1 year post-transplantPopulation: Analysis Population includes transplanted participants
Grade 2 and 3 infections, as defined by the BMT CTN Technical Manual of Procedures (MOP), are reported on the study. The cumulative incidence of infections post transplantation, treating death as a competing risk, were compared between the treatment groups using the Gray's test.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Percentage of Participants With Grade 2 and 3 Infections
6 months post-transplant
|
36.4 percentage of participants
Interval 29.8 to 43.0
|
24.1 percentage of participants
Interval 18.6 to 30.1
|
|
Percentage of Participants With Grade 2 and 3 Infections
1 year post-transplant
|
40.0 percentage of participants
Interval 33.2 to 46.7
|
30.4 percentage of participants
Interval 24.3 to 36.7
|
SECONDARY outcome
Timeframe: Day 100 post-transplantPopulation: Analysis Population includes transplanted participants
The cumulative incidence of initiation of systemic treatment for CMV was compared between the treatment groups using the Gray's test, with death treated as a competing risk. Estimates of the cumulative incidence of CMV reactivation are provided at Day 100 post-transplant.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Percentage of Participants With CMV at Day 100 Post-transplant
|
7.3 percentage of participants
Interval 4.3 to 11.4
|
7.1 percentage of participants
Interval 4.1 to 11.1
|
SECONDARY outcome
Timeframe: 1 year post-transplantPopulation: Analysis Population includes transplanted participants
DFS is defined as being alive and free of relapse/progression of the primary disease. The time from transplant until death or relapse/progression (DFS failure) was described for each treatment arm using the Kaplan-Meier estimator, with numbers of subjects at risk at specific time points presented for each treatment group. A multivariate Cox regression model for the hazard of death will be used to compare the treatment groups, after adjustment for baseline characteristics as described for the primary endpoint.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Percentage of Participants With Disease-Free Survival (DFS) at 1 Year Post-transplant
|
67.0 percentage of participants
Interval 60.0 to 73.0
|
62.6 percentage of participants
Interval 55.7 to 68.8
|
SECONDARY outcome
Timeframe: 1 year post-transplantPopulation: Analysis Population includes transplanted participants
The event for this endpoint OS is death from any cause post-transplant. Time to overall survival is defined as the time interval between date of transplant and date of death from any cause. Surviving participants will be censored at last follow-up or 1 year post-transplant, whichever comes first. The time from transplant until death from any cause was described graphically for each treatment arm using the Kaplan-Meier estimator, with numbers of subjects at risk at specific time points presented for each treatment group. A multivariate Cox regression model for the hazard of death will be used to compare the treatment groups, after adjustment for baseline characteristics as described for the primary endpoint.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Percentage of Participants With Overall Survival (OS) at 1 Year Post-transplant
|
76.8 percentage of participants
Interval 70.3 to 82.0
|
72.6 percentage of participants
Interval 66.0 to 78.2
|
SECONDARY outcome
Timeframe: 1 year Post-TransplantPopulation: Analysis Population includes transplanted participants
The cumulative incidence of lymphoproliferative disease at 1-year post-transplant is described with 95% confidence intervals for each treatment group using the Aalen-Johansen estimator, treating death as a competing event.
Outcome measures
| Measure |
PTCY/Tacrolimus/MMF
n=208 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 Participants
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Percentage of Participants With Lymphoproliferative Disease (PTLD) at 1 Year Post-Transplant
|
0.5 percentage of participants
Interval 0.0 to 2.6
|
0 percentage of participants
Interval 0.0 to 0.0
|
Adverse Events
PTCY/Tacrolimus/MMF
Serious events: 7 serious events
Other events: 142 other events
Deaths: 58 deaths
Tacrolimus/Methotrexate
Serious events: 14 serious events
Other events: 149 other events
Deaths: 70 deaths
Serious adverse events
| Measure |
PTCY/Tacrolimus/MMF
n=208 participants at risk
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 participants at risk
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
Blood and lymphatic system disorders
Haemolysis
|
0.00%
0/208 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
0.47%
1/212 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Cardiac disorders
Acute myocardial infarction
|
0.48%
1/208 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
0.00%
0/212 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/208 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
0.47%
1/212 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/208 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
0.47%
1/212 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/208 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
0.47%
1/212 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Gastrointestinal disorders
Diverticulum
|
0.00%
0/208 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
0.47%
1/212 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/208 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
0.47%
1/212 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
General disorders
Chest discomfort
|
0.00%
0/208 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
0.47%
1/212 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
General disorders
Mucosal inflammation
|
0.00%
0/208 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
0.47%
1/212 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/208 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
0.47%
1/212 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Infections and infestations
Sialoadenitis
|
0.00%
0/208 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
0.47%
1/212 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Injury, poisoning and procedural complications
Fall
|
0.48%
1/208 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
1.4%
3/212 • Number of events 3 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.48%
1/208 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
0.00%
0/212 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/208 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
0.47%
1/212 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Nervous system disorders
Embolic stroke
|
0.48%
1/208 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
0.00%
0/212 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.48%
1/208 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
0.00%
0/212 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Renal and urinary disorders
Acute kidney injury
|
0.48%
1/208 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
0.00%
0/212 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/208 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
0.47%
1/212 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Social circumstances
Homicide
|
0.48%
1/208 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
0.00%
0/212 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Vascular disorders
Deep vein thrombosis
|
0.48%
1/208 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
0.00%
0/212 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Vascular disorders
Embolism venous
|
0.00%
0/208 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
0.47%
1/212 • Number of events 1 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
Other adverse events
| Measure |
PTCY/Tacrolimus/MMF
n=208 participants at risk
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Mycophenolate Mofetil/Post-Transplant Cyclophosphamide: Mobilized PBSC grafts will be administered on Day 0 to all patients. Stem cells are administered through an indwelling central venous catheter.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting Day +5. Serum levels of tacrolimus will be measured at Day +7 and then should be checked weekly thereafter, the dose adjusted accordingly to maintain a suggested level of 5-15 ng/mL. Tacrolimus taper can be initiated at 90 days post HCT if there is no evidence of active GVHD. The tapering rate will be based on institutional practices, patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Mycophenolate Mofetil: MMF will be given at a dose of 15 mg/kg/dose ter in die (TID) with the maximum total daily dose not to exceed 3 grams (1g TID, IV or PO). MMF prophylaxis will start Day +5 and discontinue after the last dose on Day +35, or may be continued if active GVHD is present.
Cyclophosphamide: Cyclophosphamide \[50 mg/kg ideal body weight (IBW); if actual body weight (ABW) \< IBW, use ABW\] will be given on Day +3 (between 60 and 72 hours after the start of the PBSC infusion) and on Day +4 post-transplant (approximately 24 hours after Day +3 cyclophosphamide). Cyclophosphamide will be given as an IV infusion over 1-2 hours.
|
Tacrolimus/Methotrexate
n=212 participants at risk
Mobilized Peripheral Blood Stem Cell graft with Tacrolimus/Methotrexate: Mobilized PBSC grafts will be administered on Day 0 to all patients according to individual institutional guidelines after appropriate processing and quantification has been performed by the local laboratory. Stem cells are administered through an indwelling central venous catheter. If infusion occurs over two days, Day 0 is the first day the infusion is initiated.
Tacrolimus: Tacrolimus will be given per institutional practices, orally at a dose of 0.05-0.06 mg/kg/day or intravenously at a dose of 0.02-0.03 mg/kg/day starting on Day -3. Subsequent dosing will be based on blood levels per institutional guidelines with a suggested range of 5-15. If patients are on medications which alter the metabolism of tacrolimus, the initial starting dose and subsequent doses should be altered as per institutional practices. Tacrolimus taper can be initiated at a minimum of 90 days post HCT if there is no evidence of active GVHD. The rate of tapering will be done according institutional practices and patients should be off tacrolimus by Day 180 post HCT if there is no evidence of active GVHD.
Methotrexate: Methotrexate will be administered at the doses of 15 mg/m2 IV bolus on Day +1, and 10 mg/m2 IV bolus on Days +3, +6 and +11 after hematopoietic stem cell infusion. Methotrexate should be dose reduced, given with leucovorin rescue, or held for complications such as severe mucositis per institutional guidelines.
|
|---|---|---|
|
General disorders
Grades 3-5 General Disorders
|
24.5%
51/208 • Number of events 68 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
22.6%
48/212 • Number of events 61 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Immune system disorders
Grades 3-5 Immune System Disorders
|
2.4%
5/208 • Number of events 5 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
2.8%
6/212 • Number of events 6 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Gastrointestinal disorders
Grades 3-5 GI Disorders
|
27.4%
57/208 • Number of events 73 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
36.3%
77/212 • Number of events 116 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Renal and urinary disorders
Grades 3-5 Renal Disorders
|
15.9%
33/208 • Number of events 46 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
14.2%
30/212 • Number of events 42 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Vascular disorders
Grades 3-5 Hemorrhagic Disorders
|
5.8%
12/208 • Number of events 13 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
5.2%
11/212 • Number of events 11 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Cardiac disorders
Grades 3-5 Cardiac Disorders
|
34.1%
71/208 • Number of events 117 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
34.0%
72/212 • Number of events 125 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Nervous system disorders
Grades 3-5 Nervous System Disorders
|
5.8%
12/208 • Number of events 13 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
9.4%
20/212 • Number of events 25 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Blood and lymphatic system disorders
Grades 3-5 Blood and Lymphatic Disorders
|
1.4%
3/208 • Number of events 4 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
1.4%
3/212 • Number of events 4 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Vascular disorders
Grades 3-5 Vascular Disorders
|
2.9%
6/208 • Number of events 7 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
5.7%
12/212 • Number of events 13 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Musculoskeletal and connective tissue disorders
Grades 3-5 Musculoskeletal and Connective Tissue Disorders
|
8.2%
17/208 • Number of events 18 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
5.7%
12/212 • Number of events 15 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Respiratory, thoracic and mediastinal disorders
Grades 3-5 Respiratory, Thoracic and Mediastinal Disorders
|
19.7%
41/208 • Number of events 58 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
19.8%
42/212 • Number of events 52 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Metabolism and nutrition disorders
Grades 3-5 Metabolism and Nutrition Disorders
|
11.5%
24/208 • Number of events 31 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
15.6%
33/212 • Number of events 51 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Hepatobiliary disorders
Grades 3-5 Hepatic Disorders
|
11.5%
24/208 • Number of events 30 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
20.8%
44/212 • Number of events 54 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Renal and urinary disorders
Received Dialysis
|
5.3%
11/208 • Number of events 17 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
3.8%
8/212 • Number of events 11 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Hepatobiliary disorders
Hepatitis
|
2.9%
6/208 • Number of events 8 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
1.9%
4/212 • Number of events 9 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Hepatobiliary disorders
Liver failure
|
0.96%
2/208 • Number of events 2 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
1.9%
4/212 • Number of events 4 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
|
Hepatobiliary disorders
Abnormal liver function
|
6.7%
14/208 • Number of events 19 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
7.1%
15/212 • Number of events 19 • Deaths were assessed for all randomized participants. Adverse Events were assessed only for participants who underwent transplant throughout the study, an average of 1 year. More deaths are reported in the AE module than that in the secondary outcome section because deaths reported in the AE module were counted starting at randomization and throughout the study, whereas deaths reported in survival analysis were counted starting at transplant and throughout one-year post-transplant.
AE reporting was conducted according to the BMT CTN's Manual of Operating Procedures. Unexpected, serious AEs (SAEs) were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 at regular intervals. Any expected life-threatening SAE not collected as toxicities were reported through the expedited AE reporting system.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place