Trial Outcomes & Findings for Double Cord Versus Haploidentical (BMT CTN 1101) (NCT NCT01597778)
NCT ID: NCT01597778
Last Updated: 2021-12-01
Results Overview
The primary endpoint is PFS at 2 years post-randomization. Death or disease relapse/progression will be considered as events. The time to event is defined as the time interval from randomization to relapse/progression, to death or to last follow-up, whichever comes first. Relapse is defined by either morphological or cytogenetic evidence of acute leukemia consistent with pre-transplant features, or radiologic evidence of progressive lymphoma. Minimal residual disease will not be considered evidence of relapse, however, minimal residual disease that progresses will be considered as relapse and the date of relapse will be the date of detection of minimal residual disease that prompted an intervention by the treating physician. Finally, institution of any therapy to treat persistent, progressive or relapsed disease, including withdrawal of immunosuppressive therapy or DLI, will be considered evidence of relapse/progression regardless of whether the criteria described above are met.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
368 participants
Primary outcome timeframe
Year 2
Results posted on
2021-12-01
Participant Flow
Participant milestones
| Measure |
dUCB
Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen.
Double unrelated cord blood Transplant: The conditioning regimen consists of:
* Fludarabine 40 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide 50 mg/kg IV Day -6
* Total Body Irradiation (TBI): - 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the last 3 months or an autologous transplant within 24 months of enrollment; - 300 cGY Day -1 for patients who have not received cytotoxic chemotherapy within 3 months of enrollment or an autologous transplant within 24 months of enrollment
* Day 0 will be the day of the double UCB transplant
The GVHD prophylaxis regimen consists of:
* Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL. Tacrolimus (trough level of 5-15 ng/mL) may be substituted for cyclosporine if the patient is intolerant of cyclosporine or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day-3 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
Haplo-BM
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
* Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5
* Total body irradiation (TBI) 200cGy Day -1
* Day 0 will be the day of infusion of non-T-cell depleted bone marrow
The GVHD prophylaxis regimen consists of:
* Cy 50 mg/kg IV Days 3, 4
* Tacrolimus (IV or PO) beginning Day 5 with dose adjusted to maintain a trough level of 5-15 ng/mL. Cyclosporine (trough level of 200-400 ng/mL) may be substituted for tacrolimus if the patient is intolerant of tacrolimus or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
|---|---|---|
|
Overall Study
STARTED
|
186
|
182
|
|
Overall Study
COMPLETED
|
172
|
153
|
|
Overall Study
NOT COMPLETED
|
14
|
29
|
Reasons for withdrawal
| Measure |
dUCB
Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen.
Double unrelated cord blood Transplant: The conditioning regimen consists of:
* Fludarabine 40 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide 50 mg/kg IV Day -6
* Total Body Irradiation (TBI): - 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the last 3 months or an autologous transplant within 24 months of enrollment; - 300 cGY Day -1 for patients who have not received cytotoxic chemotherapy within 3 months of enrollment or an autologous transplant within 24 months of enrollment
* Day 0 will be the day of the double UCB transplant
The GVHD prophylaxis regimen consists of:
* Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL. Tacrolimus (trough level of 5-15 ng/mL) may be substituted for cyclosporine if the patient is intolerant of cyclosporine or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day-3 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
Haplo-BM
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
* Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5
* Total body irradiation (TBI) 200cGy Day -1
* Day 0 will be the day of infusion of non-T-cell depleted bone marrow
The GVHD prophylaxis regimen consists of:
* Cy 50 mg/kg IV Days 3, 4
* Tacrolimus (IV or PO) beginning Day 5 with dose adjusted to maintain a trough level of 5-15 ng/mL. Cyclosporine (trough level of 200-400 ng/mL) may be substituted for tacrolimus if the patient is intolerant of tacrolimus or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
|---|---|---|
|
Overall Study
Death
|
7
|
10
|
|
Overall Study
Withdrawal by Subject
|
3
|
4
|
|
Overall Study
Adverse Event
|
1
|
1
|
|
Overall Study
Protocol Violation
|
1
|
11
|
|
Overall Study
Transplanted off protocol
|
2
|
3
|
Baseline Characteristics
Disease risk is assessed in enrolled Leukemia patients.
Baseline characteristics by cohort
| Measure |
dUCB
n=186 Participants
Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen.
Double unrelated cord blood Transplant: The conditioning regimen consists of:
* Fludarabine 40 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide 50 mg/kg IV Day -6
* Total Body Irradiation (TBI): - 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the last 3 months or an autologous transplant within 24 months of enrollment; - 300 cGY Day -1 for patients who have not received cytotoxic chemotherapy within 3 months of enrollment or an autologous transplant within 24 months of enrollment
* Day 0 will be the day of the double UCB transplant
The GVHD prophylaxis regimen consists of:
* Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL. Tacrolimus (trough level of 5-15 ng/mL) may be substituted for cyclosporine if the patient is intolerant of cyclosporine or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day-3 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
Haplo-BM
n=182 Participants
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
* Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5
* Total body irradiation (TBI) 200cGy Day -1
* Day 0 will be the day of infusion of non-T-cell depleted bone marrow
The GVHD prophylaxis regimen consists of:
* Cy 50 mg/kg IV Days 3, 4
* Tacrolimus (IV or PO) beginning Day 5 with dose adjusted to maintain a trough level of 5-15 ng/mL. Cyclosporine (trough level of 200-400 ng/mL) may be substituted for tacrolimus if the patient is intolerant of tacrolimus or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
Total
n=368 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
Median (Range)
|
58.2 years
n=186 Participants
|
59.9 years
n=182 Participants
|
58.8 years
n=368 Participants
|
|
Sex: Female, Male
Female
|
89 Participants
n=186 Participants
|
76 Participants
n=182 Participants
|
165 Participants
n=368 Participants
|
|
Sex: Female, Male
Male
|
97 Participants
n=186 Participants
|
106 Participants
n=182 Participants
|
203 Participants
n=368 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
22 Participants
n=186 Participants
|
21 Participants
n=182 Participants
|
43 Participants
n=368 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
164 Participants
n=186 Participants
|
159 Participants
n=182 Participants
|
323 Participants
n=368 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=186 Participants
|
2 Participants
n=182 Participants
|
2 Participants
n=368 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
3 Participants
n=186 Participants
|
1 Participants
n=182 Participants
|
4 Participants
n=368 Participants
|
|
Race (NIH/OMB)
Asian
|
9 Participants
n=186 Participants
|
15 Participants
n=182 Participants
|
24 Participants
n=368 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=186 Participants
|
1 Participants
n=182 Participants
|
1 Participants
n=368 Participants
|
|
Race (NIH/OMB)
Black or African American
|
27 Participants
n=186 Participants
|
34 Participants
n=182 Participants
|
61 Participants
n=368 Participants
|
|
Race (NIH/OMB)
White
|
145 Participants
n=186 Participants
|
126 Participants
n=182 Participants
|
271 Participants
n=368 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=186 Participants
|
0 Participants
n=182 Participants
|
0 Participants
n=368 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=186 Participants
|
5 Participants
n=182 Participants
|
7 Participants
n=368 Participants
|
|
Karnofsky Performance Score
>=90
|
126 Participants
n=186 Participants
|
111 Participants
n=182 Participants
|
237 Participants
n=368 Participants
|
|
Karnofsky Performance Score
<90
|
59 Participants
n=186 Participants
|
71 Participants
n=182 Participants
|
130 Participants
n=368 Participants
|
|
Karnofsky Performance Score
Missing
|
1 Participants
n=186 Participants
|
0 Participants
n=182 Participants
|
1 Participants
n=368 Participants
|
|
Primary Diagnosis
Acute Lymphoblastic Leukemia
|
31 Participants
n=186 Participants
|
32 Participants
n=182 Participants
|
63 Participants
n=368 Participants
|
|
Primary Diagnosis
Acute Myelogeneous Leukemia
|
98 Participants
n=186 Participants
|
98 Participants
n=182 Participants
|
196 Participants
n=368 Participants
|
|
Primary Diagnosis
Biphenotypic/Undifferentiated/Prolymphocytic Leukemia
|
1 Participants
n=186 Participants
|
5 Participants
n=182 Participants
|
6 Participants
n=368 Participants
|
|
Primary Diagnosis
Hodgkin's Lymphoma
|
10 Participants
n=186 Participants
|
8 Participants
n=182 Participants
|
18 Participants
n=368 Participants
|
|
Primary Diagnosis
Large Cell Lymphoma
|
21 Participants
n=186 Participants
|
19 Participants
n=182 Participants
|
40 Participants
n=368 Participants
|
|
Primary Diagnosis
Follicular Non-Hodgkin's Lymphoma
|
7 Participants
n=186 Participants
|
5 Participants
n=182 Participants
|
12 Participants
n=368 Participants
|
|
Primary Diagnosis
T-cell Leukemia/Lymphoma
|
4 Participants
n=186 Participants
|
3 Participants
n=182 Participants
|
7 Participants
n=368 Participants
|
|
Primary Diagnosis
Mantle Cell Lymphoma
|
6 Participants
n=186 Participants
|
5 Participants
n=182 Participants
|
11 Participants
n=368 Participants
|
|
Primary Diagnosis
Other Lymphoma
|
8 Participants
n=186 Participants
|
7 Participants
n=182 Participants
|
15 Participants
n=368 Participants
|
|
Disease Risk for Leukemia Patients (N=272)
First Complete Remission
|
99 Participants
n=134 Participants • Disease risk is assessed in enrolled Leukemia patients.
|
117 Participants
n=138 Participants • Disease risk is assessed in enrolled Leukemia patients.
|
216 Participants
n=272 Participants • Disease risk is assessed in enrolled Leukemia patients.
|
|
Disease Risk for Leukemia Patients (N=272)
Second Complete Remission
|
35 Participants
n=134 Participants • Disease risk is assessed in enrolled Leukemia patients.
|
20 Participants
n=138 Participants • Disease risk is assessed in enrolled Leukemia patients.
|
55 Participants
n=272 Participants • Disease risk is assessed in enrolled Leukemia patients.
|
|
Disease Risk for Leukemia Patients (N=272)
Third or More
|
0 Participants
n=134 Participants • Disease risk is assessed in enrolled Leukemia patients.
|
1 Participants
n=138 Participants • Disease risk is assessed in enrolled Leukemia patients.
|
1 Participants
n=272 Participants • Disease risk is assessed in enrolled Leukemia patients.
|
|
Disease Risk for Lymphoma Patients (N=96)
Complete Response
|
20 Participants
n=52 Participants • Disease risk is assessed in enrolled Lymphoma patients.
|
14 Participants
n=44 Participants • Disease risk is assessed in enrolled Lymphoma patients.
|
34 Participants
n=96 Participants • Disease risk is assessed in enrolled Lymphoma patients.
|
|
Disease Risk for Lymphoma Patients (N=96)
Partial Response
|
25 Participants
n=52 Participants • Disease risk is assessed in enrolled Lymphoma patients.
|
25 Participants
n=44 Participants • Disease risk is assessed in enrolled Lymphoma patients.
|
50 Participants
n=96 Participants • Disease risk is assessed in enrolled Lymphoma patients.
|
|
Disease Risk for Lymphoma Patients (N=96)
Follicular or Non-Hodgkin's
|
7 Participants
n=52 Participants • Disease risk is assessed in enrolled Lymphoma patients.
|
5 Participants
n=44 Participants • Disease risk is assessed in enrolled Lymphoma patients.
|
12 Participants
n=96 Participants • Disease risk is assessed in enrolled Lymphoma patients.
|
|
Cytogenetics for Leukemia
Favorable
|
17 Participants
n=134 Participants • Cytogenetics data on leukemia participants were retrieved from CIBMTR. Data is only measured in enrolled Leukemia patients.
|
20 Participants
n=138 Participants • Cytogenetics data on leukemia participants were retrieved from CIBMTR. Data is only measured in enrolled Leukemia patients.
|
37 Participants
n=272 Participants • Cytogenetics data on leukemia participants were retrieved from CIBMTR. Data is only measured in enrolled Leukemia patients.
|
|
Cytogenetics for Leukemia
Intermediate
|
61 Participants
n=134 Participants • Cytogenetics data on leukemia participants were retrieved from CIBMTR. Data is only measured in enrolled Leukemia patients.
|
56 Participants
n=138 Participants • Cytogenetics data on leukemia participants were retrieved from CIBMTR. Data is only measured in enrolled Leukemia patients.
|
117 Participants
n=272 Participants • Cytogenetics data on leukemia participants were retrieved from CIBMTR. Data is only measured in enrolled Leukemia patients.
|
|
Cytogenetics for Leukemia
Poor
|
43 Participants
n=134 Participants • Cytogenetics data on leukemia participants were retrieved from CIBMTR. Data is only measured in enrolled Leukemia patients.
|
45 Participants
n=138 Participants • Cytogenetics data on leukemia participants were retrieved from CIBMTR. Data is only measured in enrolled Leukemia patients.
|
88 Participants
n=272 Participants • Cytogenetics data on leukemia participants were retrieved from CIBMTR. Data is only measured in enrolled Leukemia patients.
|
|
Cytogenetics for Leukemia
Not Available
|
13 Participants
n=134 Participants • Cytogenetics data on leukemia participants were retrieved from CIBMTR. Data is only measured in enrolled Leukemia patients.
|
17 Participants
n=138 Participants • Cytogenetics data on leukemia participants were retrieved from CIBMTR. Data is only measured in enrolled Leukemia patients.
|
30 Participants
n=272 Participants • Cytogenetics data on leukemia participants were retrieved from CIBMTR. Data is only measured in enrolled Leukemia patients.
|
|
HLA Matching Score for Haploidentical Donor at Randomization
3/6
|
46 Participants
n=186 Participants
|
39 Participants
n=182 Participants
|
85 Participants
n=368 Participants
|
|
HLA Matching Score for Haploidentical Donor at Randomization
4/6
|
22 Participants
n=186 Participants
|
16 Participants
n=182 Participants
|
38 Participants
n=368 Participants
|
|
HLA Matching Score for Haploidentical Donor at Randomization
4/8
|
0 Participants
n=186 Participants
|
1 Participants
n=182 Participants
|
1 Participants
n=368 Participants
|
|
HLA Matching Score for Haploidentical Donor at Randomization
5/8
|
1 Participants
n=186 Participants
|
0 Participants
n=182 Participants
|
1 Participants
n=368 Participants
|
|
HLA Matching Score for Haploidentical Donor at Randomization
6/8
|
1 Participants
n=186 Participants
|
1 Participants
n=182 Participants
|
2 Participants
n=368 Participants
|
|
HLA Matching Score for Haploidentical Donor at Randomization
Not Required*
|
116 Participants
n=186 Participants
|
125 Participants
n=182 Participants
|
241 Participants
n=368 Participants
|
|
HLA Matching Score for Cord Blood Unit 1 at Enrollment
4/6
|
83 Participants
n=186 Participants
|
82 Participants
n=182 Participants
|
165 Participants
n=368 Participants
|
|
HLA Matching Score for Cord Blood Unit 1 at Enrollment
5/6
|
73 Participants
n=186 Participants
|
75 Participants
n=182 Participants
|
148 Participants
n=368 Participants
|
|
HLA Matching Score for Cord Blood Unit 1 at Enrollment
6/6
|
30 Participants
n=186 Participants
|
25 Participants
n=182 Participants
|
55 Participants
n=368 Participants
|
|
HLA Matching Score for Cord Blood Unit 2 at Enrollment
4/6
|
99 Participants
n=186 Participants
|
99 Participants
n=182 Participants
|
198 Participants
n=368 Participants
|
|
HLA Matching Score for Cord Blood Unit 2 at Enrollment
5/6
|
66 Participants
n=186 Participants
|
64 Participants
n=182 Participants
|
130 Participants
n=368 Participants
|
|
HLA Matching Score for Cord Blood Unit 2 at Enrollment
6/6
|
21 Participants
n=186 Participants
|
19 Participants
n=182 Participants
|
40 Participants
n=368 Participants
|
|
Pre-cryopreservation total nucleated cell count
|
5.13 cells x 10^7/kg
n=166 Participants • Statistics is summarized on available data.
|
5.59 cells x 10^7/kg
n=11 Participants • Statistics is summarized on available data.
|
5.15 cells x 10^7/kg
n=177 Participants • Statistics is summarized on available data.
|
|
Post-thaw total nucleated cell count
|
4.32 cells x 10^7/kg
n=72 Participants • Statistics is summarized on available data.
|
3.12 cells x 10^7/kg
n=5 Participants • Statistics is summarized on available data.
|
4.32 cells x 10^7/kg
n=77 Participants • Statistics is summarized on available data.
|
|
Total nucleated cell count at infusion
|
2.95 cells x 10^7/kg
n=167 Participants • Statistics is summarized on available data.
|
26.82 cells x 10^7/kg
n=121 Participants • Statistics is summarized on available data.
|
4.46 cells x 10^7/kg
n=288 Participants • Statistics is summarized on available data.
|
|
Pre-cryopreservation CD34+ cell count
|
0.23 cells x 10^6/kg
n=157 Participants • Statistics is summarized on available data.
|
0.21 cells x 10^6/kg
n=11 Participants • Statistics is summarized on available data.
|
0.22 cells x 10^6/kg
n=168 Participants • Statistics is summarized on available data.
|
|
Post-thaw CD34+ cell count
|
0.20 cells x 10^6/kg
n=66 Participants • Statistics is summarized on available data.
|
0.17 cells x 10^6/kg
n=5 Participants • Statistics is summarized on available data.
|
0.20 cells x 10^6/kg
n=71 Participants • Statistics is summarized on available data.
|
|
CD34+ cell count at infusion
|
0.13 cells x 10^6/kg
n=155 Participants • Statistics is summarized on available data.
|
2.87 cells x 10^6/kg
n=73 Participants • Statistics is summarized on available data.
|
0.20 cells x 10^6/kg
n=228 Participants • Statistics is summarized on available data.
|
|
Pre-cryopreservation CD3+ cell count
|
7.79 cells x 10^6/kg
n=7 Participants • Statistics is summarized on available data.
|
0.00 cells x 10^6/kg
n=1 Participants • Statistics is summarized on available data.
|
7.38 cells x 10^6/kg
n=8 Participants • Statistics is summarized on available data.
|
|
Post-thaw CD3+ cell count
|
6.97 cells x 10^6/kg
n=49 Participants • Statistics is summarized on available data.
|
7.47 cells x 10^6/kg
n=2 Participants • Statistics is summarized on available data.
|
6.97 cells x 10^6/kg
n=51 Participants • Statistics is summarized on available data.
|
|
CD3+ cell count at infusion
|
5.50 cells x 10^6/kg
n=111 Participants • Statistics is summarized on available data.
|
29.66 cells x 10^6/kg
n=71 Participants • Statistics is summarized on available data.
|
8.05 cells x 10^6/kg
n=182 Participants • Statistics is summarized on available data.
|
|
HCT-comorbidity index (CI)
>=3
|
71 Participants
n=175 Participants • HCT-CI was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
68 Participants
n=167 Participants • HCT-CI was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
139 Participants
n=342 Participants • HCT-CI was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
|
HCT-comorbidity index (CI)
2
|
26 Participants
n=175 Participants • HCT-CI was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
23 Participants
n=167 Participants • HCT-CI was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
49 Participants
n=342 Participants • HCT-CI was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
|
HCT-comorbidity index (CI)
1
|
26 Participants
n=175 Participants • HCT-CI was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
23 Participants
n=167 Participants • HCT-CI was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
49 Participants
n=342 Participants • HCT-CI was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
|
HCT-comorbidity index (CI)
0
|
52 Participants
n=175 Participants • HCT-CI was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
53 Participants
n=167 Participants • HCT-CI was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
105 Participants
n=342 Participants • HCT-CI was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
|
CMV Status at Transplant
Positive
|
98 Participants
n=175 Participants • CMV status was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
99 Participants
n=167 Participants • CMV status was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
197 Participants
n=342 Participants • CMV status was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
|
CMV Status at Transplant
Negative
|
76 Participants
n=175 Participants • CMV status was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
68 Participants
n=167 Participants • CMV status was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
144 Participants
n=342 Participants • CMV status was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
|
CMV Status at Transplant
Missing
|
1 Participants
n=175 Participants • CMV status was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
0 Participants
n=167 Participants • CMV status was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
1 Participants
n=342 Participants • CMV status was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
|
Time from Diagnosis to Transplant
|
283 day
n=175 Participants • Time to transplant was only calculated in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
219 day
n=167 Participants • Time to transplant was only calculated in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
233 day
n=342 Participants • Time to transplant was only calculated in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
|
Prior Autologous Transplant
Prior Autologous Transplant
|
16 Participants
n=186 Participants
|
16 Participants
n=182 Participants
|
32 Participants
n=368 Participants
|
|
Prior Autologous Transplant
No Prior Autologous Transplant
|
170 Participants
n=186 Participants
|
166 Participants
n=182 Participants
|
336 Participants
n=368 Participants
|
|
Number of Regimens Prior to Transplant
5
|
4 Participants
n=175 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
7 Participants
n=167 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
11 Participants
n=342 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
|
Number of Regimens Prior to Transplant
4
|
6 Participants
n=175 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
6 Participants
n=167 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
12 Participants
n=342 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
|
Number of Regimens Prior to Transplant
3
|
14 Participants
n=175 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
8 Participants
n=167 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
22 Participants
n=342 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
|
Number of Regimens Prior to Transplant
2
|
8 Participants
n=175 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
10 Participants
n=167 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
18 Participants
n=342 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
|
Number of Regimens Prior to Transplant
1
|
17 Participants
n=175 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
10 Participants
n=167 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
27 Participants
n=342 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
|
Number of Regimens Prior to Transplant
0
|
2 Participants
n=175 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
0 Participants
n=167 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
2 Participants
n=342 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
|
Number of Regimens Prior to Transplant
Unknown
|
124 Participants
n=175 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
126 Participants
n=167 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
250 Participants
n=342 Participants • Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted.
|
|
Disease Risk Index
Low
|
23 Participants
n=186 Participants
|
14 Participants
n=182 Participants
|
37 Participants
n=368 Participants
|
|
Disease Risk Index
Intermediate
|
119 Participants
n=186 Participants
|
120 Participants
n=182 Participants
|
239 Participants
n=368 Participants
|
|
Disease Risk Index
High
|
35 Participants
n=186 Participants
|
37 Participants
n=182 Participants
|
72 Participants
n=368 Participants
|
|
Disease Risk Index
Not Available
|
9 Participants
n=186 Participants
|
11 Participants
n=182 Participants
|
20 Participants
n=368 Participants
|
PRIMARY outcome
Timeframe: Year 2Population: The primary endpoint analysis is performed using the intent-to-treat principle so that all randomized patients are included in the analysis.
The primary endpoint is PFS at 2 years post-randomization. Death or disease relapse/progression will be considered as events. The time to event is defined as the time interval from randomization to relapse/progression, to death or to last follow-up, whichever comes first. Relapse is defined by either morphological or cytogenetic evidence of acute leukemia consistent with pre-transplant features, or radiologic evidence of progressive lymphoma. Minimal residual disease will not be considered evidence of relapse, however, minimal residual disease that progresses will be considered as relapse and the date of relapse will be the date of detection of minimal residual disease that prompted an intervention by the treating physician. Finally, institution of any therapy to treat persistent, progressive or relapsed disease, including withdrawal of immunosuppressive therapy or DLI, will be considered evidence of relapse/progression regardless of whether the criteria described above are met.
Outcome measures
| Measure |
dUCB
n=186 Participants
Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen.
Double unrelated cord blood Transplant: The conditioning regimen consists of:
* Fludarabine 40 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide 50 mg/kg IV Day -6
* Total Body Irradiation (TBI): - 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the last 3 months or an autologous transplant within 24 months of enrollment; - 300 cGY Day -1 for patients who have not received cytotoxic chemotherapy within 3 months of enrollment or an autologous transplant within 24 months of enrollment
* Day 0 will be the day of the double UCB transplant
The GVHD prophylaxis regimen consists of:
* Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL. Tacrolimus (trough level of 5-15 ng/mL) may be substituted for cyclosporine if the patient is intolerant of cyclosporine or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day-3 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
Haplo-BM
n=182 Participants
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
* Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5
* Total body irradiation (TBI) 200cGy Day -1
* Day 0 will be the day of infusion of non-T-cell depleted bone marrow
The GVHD prophylaxis regimen consists of:
* Cy 50 mg/kg IV Days 3, 4
* Tacrolimus (IV or PO) beginning Day 5 with dose adjusted to maintain a trough level of 5-15 ng/mL. Cyclosporine (trough level of 200-400 ng/mL) may be substituted for tacrolimus if the patient is intolerant of tacrolimus or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
|---|---|---|
|
Percentage of Participants With Progression Free Survival (PFS)
|
35.0 percentage of participants
Interval 28.0 to 42.1
|
41.1 percentage of participants
Interval 33.6 to 48.4
|
SECONDARY outcome
Timeframe: Year 2Population: The randomized participants are included in the analysis.
Participants' primary diagnosis was categorized into two large groups: leukemia versus lymphoma. Age was dichotomized into two large groups: age \<= 59 versus age \> 59. The Kaplan-Meier estimate for PFS at 2 years post-randomization are provided for each subgroup.
Outcome measures
| Measure |
dUCB
n=186 Participants
Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen.
Double unrelated cord blood Transplant: The conditioning regimen consists of:
* Fludarabine 40 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide 50 mg/kg IV Day -6
* Total Body Irradiation (TBI): - 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the last 3 months or an autologous transplant within 24 months of enrollment; - 300 cGY Day -1 for patients who have not received cytotoxic chemotherapy within 3 months of enrollment or an autologous transplant within 24 months of enrollment
* Day 0 will be the day of the double UCB transplant
The GVHD prophylaxis regimen consists of:
* Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL. Tacrolimus (trough level of 5-15 ng/mL) may be substituted for cyclosporine if the patient is intolerant of cyclosporine or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day-3 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
Haplo-BM
n=182 Participants
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
* Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5
* Total body irradiation (TBI) 200cGy Day -1
* Day 0 will be the day of infusion of non-T-cell depleted bone marrow
The GVHD prophylaxis regimen consists of:
* Cy 50 mg/kg IV Days 3, 4
* Tacrolimus (IV or PO) beginning Day 5 with dose adjusted to maintain a trough level of 5-15 ng/mL. Cyclosporine (trough level of 200-400 ng/mL) may be substituted for tacrolimus if the patient is intolerant of tacrolimus or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
|---|---|---|
|
Percentage of Participants With PFS by Treatment Arms in Subgroups
By Primary Disease of Leukemia
|
34.8 percentage of participants
Interval 26.6 to 43.1
|
41.7 percentage of participants
Interval 33.0 to 50.1
|
|
Percentage of Participants With PFS by Treatment Arms in Subgroups
By Primary Disease of Lymphoma
|
35.6 percentage of participants
Interval 22.7 to 48.6
|
39.3 percentage of participants
Interval 24.7 to 53.5
|
|
Percentage of Participants With PFS by Treatment Arms in Subgroups
By Age Group <= 59 years
|
37.9 percentage of participants
Interval 28.2 to 47.5
|
39.6 percentage of participants
Interval 28.8 to 50.2
|
|
Percentage of Participants With PFS by Treatment Arms in Subgroups
By Age Group > 59 years
|
31.6 percentage of participants
Interval 21.8 to 41.9
|
42.4 percentage of participants
Interval 32.1 to 52.3
|
SECONDARY outcome
Timeframe: Day 56Population: The transplanted participants are included in the analysis. A total of 26 patients (11 on the dUCB arm and 15 on the Haplo-BM arm) who did not proceed to the study transplant are excluded.
Neutrophil recovery is defined as achieving an absolute neutrophil count 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.
Outcome measures
| Measure |
dUCB
n=175 Participants
Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen.
Double unrelated cord blood Transplant: The conditioning regimen consists of:
* Fludarabine 40 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide 50 mg/kg IV Day -6
* Total Body Irradiation (TBI): - 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the last 3 months or an autologous transplant within 24 months of enrollment; - 300 cGY Day -1 for patients who have not received cytotoxic chemotherapy within 3 months of enrollment or an autologous transplant within 24 months of enrollment
* Day 0 will be the day of the double UCB transplant
The GVHD prophylaxis regimen consists of:
* Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL. Tacrolimus (trough level of 5-15 ng/mL) may be substituted for cyclosporine if the patient is intolerant of cyclosporine or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day-3 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
Haplo-BM
n=167 Participants
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
* Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5
* Total body irradiation (TBI) 200cGy Day -1
* Day 0 will be the day of infusion of non-T-cell depleted bone marrow
The GVHD prophylaxis regimen consists of:
* Cy 50 mg/kg IV Days 3, 4
* Tacrolimus (IV or PO) beginning Day 5 with dose adjusted to maintain a trough level of 5-15 ng/mL. Cyclosporine (trough level of 200-400 ng/mL) may be substituted for tacrolimus if the patient is intolerant of tacrolimus or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
|---|---|---|
|
Percentage of Participants With Neutrophil Recovery
|
94.9 percentage of participants
Interval 90.2 to 97.4
|
98.8 percentage of participants
Interval 94.3 to 99.8
|
SECONDARY outcome
Timeframe: Day 100Population: The transplanted participants are included in the analysis. A total of 26 patients (11 on the dUCB arm and 15 on the Haplo-BM arm) who did not proceed to the study transplant are excluded.
Platelet recovery is defined by two different metrics as the first day of a sustained platelet count greater than 20,000/mm\^3 or greater than 50,000/mm\^3 with no platelet transfusions in the preceding seven days. The first day of the sustained platelet count will be designated the day of platelet engraftment.
Outcome measures
| Measure |
dUCB
n=175 Participants
Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen.
Double unrelated cord blood Transplant: The conditioning regimen consists of:
* Fludarabine 40 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide 50 mg/kg IV Day -6
* Total Body Irradiation (TBI): - 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the last 3 months or an autologous transplant within 24 months of enrollment; - 300 cGY Day -1 for patients who have not received cytotoxic chemotherapy within 3 months of enrollment or an autologous transplant within 24 months of enrollment
* Day 0 will be the day of the double UCB transplant
The GVHD prophylaxis regimen consists of:
* Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL. Tacrolimus (trough level of 5-15 ng/mL) may be substituted for cyclosporine if the patient is intolerant of cyclosporine or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day-3 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
Haplo-BM
n=167 Participants
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
* Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5
* Total body irradiation (TBI) 200cGy Day -1
* Day 0 will be the day of infusion of non-T-cell depleted bone marrow
The GVHD prophylaxis regimen consists of:
* Cy 50 mg/kg IV Days 3, 4
* Tacrolimus (IV or PO) beginning Day 5 with dose adjusted to maintain a trough level of 5-15 ng/mL. Cyclosporine (trough level of 200-400 ng/mL) may be substituted for tacrolimus if the patient is intolerant of tacrolimus or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
|---|---|---|
|
Percentage of Participants With Platelet Recovery
Platelet recovery to 20K
|
86.9 percentage of participants
Interval 80.8 to 91.2
|
91.6 percentage of participants
Interval 86.1 to 95.0
|
|
Percentage of Participants With Platelet Recovery
Platelet recovery to 50K
|
78.3 percentage of participants
Interval 71.4 to 83.7
|
84.4 percentage of participants
Interval 77.9 to 89.1
|
SECONDARY outcome
Timeframe: Day 56Population: The transplanted participants are included in the analysis. A total of 26 patients (11 on the dUCB arm and 15 on the Haplo-BM arm) who did not proceed to the study transplant are excluded.
Primary graft failure is defined as less than 5% donor chimerism on all measurements up to and including Day 56.
Outcome measures
| Measure |
dUCB
n=175 Participants
Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen.
Double unrelated cord blood Transplant: The conditioning regimen consists of:
* Fludarabine 40 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide 50 mg/kg IV Day -6
* Total Body Irradiation (TBI): - 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the last 3 months or an autologous transplant within 24 months of enrollment; - 300 cGY Day -1 for patients who have not received cytotoxic chemotherapy within 3 months of enrollment or an autologous transplant within 24 months of enrollment
* Day 0 will be the day of the double UCB transplant
The GVHD prophylaxis regimen consists of:
* Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL. Tacrolimus (trough level of 5-15 ng/mL) may be substituted for cyclosporine if the patient is intolerant of cyclosporine or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day-3 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
Haplo-BM
n=167 Participants
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
* Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5
* Total body irradiation (TBI) 200cGy Day -1
* Day 0 will be the day of infusion of non-T-cell depleted bone marrow
The GVHD prophylaxis regimen consists of:
* Cy 50 mg/kg IV Days 3, 4
* Tacrolimus (IV or PO) beginning Day 5 with dose adjusted to maintain a trough level of 5-15 ng/mL. Cyclosporine (trough level of 200-400 ng/mL) may be substituted for tacrolimus if the patient is intolerant of tacrolimus or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
|---|---|---|
|
Participants With Primary Graft Failure
|
13 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: Year 2Population: The transplanted participants are included in the analysis. A total of 26 patients (11 on the dUCB arm and 15 on the Haplo-BM arm) who did not proceed to the study transplant are excluded.
Secondary graft failure is defined as initial donor chimerism ≥ 5% declining to \< 5% on subsequent measurements with time to secondary graft failure beginning at the first day of primary engraftment.
Outcome measures
| Measure |
dUCB
n=175 Participants
Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen.
Double unrelated cord blood Transplant: The conditioning regimen consists of:
* Fludarabine 40 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide 50 mg/kg IV Day -6
* Total Body Irradiation (TBI): - 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the last 3 months or an autologous transplant within 24 months of enrollment; - 300 cGY Day -1 for patients who have not received cytotoxic chemotherapy within 3 months of enrollment or an autologous transplant within 24 months of enrollment
* Day 0 will be the day of the double UCB transplant
The GVHD prophylaxis regimen consists of:
* Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL. Tacrolimus (trough level of 5-15 ng/mL) may be substituted for cyclosporine if the patient is intolerant of cyclosporine or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day-3 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
Haplo-BM
n=167 Participants
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
* Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5
* Total body irradiation (TBI) 200cGy Day -1
* Day 0 will be the day of infusion of non-T-cell depleted bone marrow
The GVHD prophylaxis regimen consists of:
* Cy 50 mg/kg IV Days 3, 4
* Tacrolimus (IV or PO) beginning Day 5 with dose adjusted to maintain a trough level of 5-15 ng/mL. Cyclosporine (trough level of 200-400 ng/mL) may be substituted for tacrolimus if the patient is intolerant of tacrolimus or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
|---|---|---|
|
Percentage of Participants With Secondary Graft Failure
|
2.6 percentage of participants
Interval 0.9 to 6.1
|
3.4 percentage of participants
Interval 1.3 to 7.2
|
SECONDARY outcome
Timeframe: Day 180Population: The transplanted participants are included in the analysis. A total of 26 patients (11 on the dUCB arm and 15 on the Haplo-BM arm) who did not proceed to the study transplant are excluded.
The cumulative incidences of grade II - IV and III - IV acute aGVHD will be determined.
Outcome measures
| Measure |
dUCB
n=175 Participants
Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen.
Double unrelated cord blood Transplant: The conditioning regimen consists of:
* Fludarabine 40 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide 50 mg/kg IV Day -6
* Total Body Irradiation (TBI): - 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the last 3 months or an autologous transplant within 24 months of enrollment; - 300 cGY Day -1 for patients who have not received cytotoxic chemotherapy within 3 months of enrollment or an autologous transplant within 24 months of enrollment
* Day 0 will be the day of the double UCB transplant
The GVHD prophylaxis regimen consists of:
* Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL. Tacrolimus (trough level of 5-15 ng/mL) may be substituted for cyclosporine if the patient is intolerant of cyclosporine or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day-3 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
Haplo-BM
n=167 Participants
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
* Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5
* Total body irradiation (TBI) 200cGy Day -1
* Day 0 will be the day of infusion of non-T-cell depleted bone marrow
The GVHD prophylaxis regimen consists of:
* Cy 50 mg/kg IV Days 3, 4
* Tacrolimus (IV or PO) beginning Day 5 with dose adjusted to maintain a trough level of 5-15 ng/mL. Cyclosporine (trough level of 200-400 ng/mL) may be substituted for tacrolimus if the patient is intolerant of tacrolimus or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
|---|---|---|
|
Percentage of Participants With Acute Graft-versus-Host Disease (aGVHD)
grade III - IV
|
8.6 percentage of participants
Interval 5.0 to 13.3
|
7.2 percentage of participants
Interval 3.9 to 11.8
|
|
Percentage of Participants With Acute Graft-versus-Host Disease (aGVHD)
grade II - IV
|
34.9 percentage of participants
Interval 27.9 to 42.0
|
28.1 percentage of participants
Interval 21.5 to 35.1
|
SECONDARY outcome
Timeframe: Year 2Population: The transplanted participants are included in the analysis. A total of 26 patients (11 on the dUCB arm and 15 on the Haplo-BM arm) who did not proceed to the study transplant are excluded.
The cumulative incidence of cGVHD from the time of transplant will be determined. Data were collected directly from providers and chart review according to the recommendations of the NIH Consensus Conference.
Outcome measures
| Measure |
dUCB
n=175 Participants
Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen.
Double unrelated cord blood Transplant: The conditioning regimen consists of:
* Fludarabine 40 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide 50 mg/kg IV Day -6
* Total Body Irradiation (TBI): - 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the last 3 months or an autologous transplant within 24 months of enrollment; - 300 cGY Day -1 for patients who have not received cytotoxic chemotherapy within 3 months of enrollment or an autologous transplant within 24 months of enrollment
* Day 0 will be the day of the double UCB transplant
The GVHD prophylaxis regimen consists of:
* Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL. Tacrolimus (trough level of 5-15 ng/mL) may be substituted for cyclosporine if the patient is intolerant of cyclosporine or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day-3 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
Haplo-BM
n=167 Participants
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
* Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5
* Total body irradiation (TBI) 200cGy Day -1
* Day 0 will be the day of infusion of non-T-cell depleted bone marrow
The GVHD prophylaxis regimen consists of:
* Cy 50 mg/kg IV Days 3, 4
* Tacrolimus (IV or PO) beginning Day 5 with dose adjusted to maintain a trough level of 5-15 ng/mL. Cyclosporine (trough level of 200-400 ng/mL) may be substituted for tacrolimus if the patient is intolerant of tacrolimus or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
|---|---|---|
|
Percentage of Participants With Chronic Graft-versus-Host Disease (cGHVD)
|
22.0 percentage of participants
Interval 16.1 to 28.5
|
26.2 percentage of participants
Interval 19.7 to 33.2
|
SECONDARY outcome
Timeframe: Year 2Population: The randomized or transplanted participants are included in the analyses.
Overall survival is defined as the time interval between date of randomization and death from any cause or for surviving patients, to last follow-up. The time interval between date of transplant and death from any cause or for surviving patients, to last follow-up are also analyzed.
Outcome measures
| Measure |
dUCB
n=186 Participants
Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen.
Double unrelated cord blood Transplant: The conditioning regimen consists of:
* Fludarabine 40 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide 50 mg/kg IV Day -6
* Total Body Irradiation (TBI): - 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the last 3 months or an autologous transplant within 24 months of enrollment; - 300 cGY Day -1 for patients who have not received cytotoxic chemotherapy within 3 months of enrollment or an autologous transplant within 24 months of enrollment
* Day 0 will be the day of the double UCB transplant
The GVHD prophylaxis regimen consists of:
* Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL. Tacrolimus (trough level of 5-15 ng/mL) may be substituted for cyclosporine if the patient is intolerant of cyclosporine or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day-3 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
Haplo-BM
n=182 Participants
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
* Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5
* Total body irradiation (TBI) 200cGy Day -1
* Day 0 will be the day of infusion of non-T-cell depleted bone marrow
The GVHD prophylaxis regimen consists of:
* Cy 50 mg/kg IV Days 3, 4
* Tacrolimus (IV or PO) beginning Day 5 with dose adjusted to maintain a trough level of 5-15 ng/mL. Cyclosporine (trough level of 200-400 ng/mL) may be substituted for tacrolimus if the patient is intolerant of tacrolimus or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
|---|---|---|
|
Percentage of Participants With Overall Survival
OS post-randomization
|
45.7 percentage of participants
Interval 38.1 to 53.0
|
57.0 percentage of participants
Interval 49.1 to 64.2
|
|
Percentage of Participants With Overall Survival
OS post-transplant
|
46.8 percentage of participants
Interval 38.9 to 54.2
|
59.4 percentage of participants
Interval 51.2 to 66.7
|
SECONDARY outcome
Timeframe: Day 100, Day 180, Year 1, and Year 2Population: The randomized or transplanted participants are included in the analyses.
The cumulative incidence of TRM will be estimated, event for this endpoint is death without evidence of disease progression or recurrence.
Outcome measures
| Measure |
dUCB
n=186 Participants
Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen.
Double unrelated cord blood Transplant: The conditioning regimen consists of:
* Fludarabine 40 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide 50 mg/kg IV Day -6
* Total Body Irradiation (TBI): - 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the last 3 months or an autologous transplant within 24 months of enrollment; - 300 cGY Day -1 for patients who have not received cytotoxic chemotherapy within 3 months of enrollment or an autologous transplant within 24 months of enrollment
* Day 0 will be the day of the double UCB transplant
The GVHD prophylaxis regimen consists of:
* Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL. Tacrolimus (trough level of 5-15 ng/mL) may be substituted for cyclosporine if the patient is intolerant of cyclosporine or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day-3 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
Haplo-BM
n=182 Participants
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
* Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5
* Total body irradiation (TBI) 200cGy Day -1
* Day 0 will be the day of infusion of non-T-cell depleted bone marrow
The GVHD prophylaxis regimen consists of:
* Cy 50 mg/kg IV Days 3, 4
* Tacrolimus (IV or PO) beginning Day 5 with dose adjusted to maintain a trough level of 5-15 ng/mL. Cyclosporine (trough level of 200-400 ng/mL) may be substituted for tacrolimus if the patient is intolerant of tacrolimus or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
|---|---|---|
|
Percentage of Participants With Treatment-related Mortality (TRM)
Day 100 Post Randomization
|
5.5 percentage of participants
Interval 2.8 to 9.4
|
3.4 percentage of participants
Interval 1.4 to 6.8
|
|
Percentage of Participants With Treatment-related Mortality (TRM)
Day 100 Post Transplant
|
6.9 percentage of participants
Interval 3.7 to 11.3
|
3.6 percentage of participants
Interval 1.5 to 7.2
|
|
Percentage of Participants With Treatment-related Mortality (TRM)
Day 180 Post Randomization
|
10.4 percentage of participants
Interval 6.5 to 15.3
|
4.5 percentage of participants
Interval 2.1 to 8.2
|
|
Percentage of Participants With Treatment-related Mortality (TRM)
Day 180 Post Transplant
|
13.1 percentage of participants
Interval 8.6 to 18.6
|
4.8 percentage of participants
Interval 2.2 to 8.8
|
|
Percentage of Participants With Treatment-related Mortality (TRM)
1 Year Post Randomization
|
14.8 percentage of participants
Interval 10.1 to 20.3
|
6.7 percentage of participants
Interval 3.7 to 11.1
|
|
Percentage of Participants With Treatment-related Mortality (TRM)
1 Year Post Transplant
|
16.0 percentage of participants
Interval 11.0 to 21.9
|
7.9 percentage of participants
Interval 4.4 to 12.7
|
|
Percentage of Participants With Treatment-related Mortality (TRM)
2 Year Post Randomization
|
17.9 percentage of participants
Interval 12.7 to 23.9
|
10.5 percentage of participants
Interval 6.5 to 15.7
|
|
Percentage of Participants With Treatment-related Mortality (TRM)
2 Year Post Transplant
|
18.6 percentage of participants
Interval 13.1 to 24.8
|
10.7 percentage of participants
Interval 6.5 to 16.1
|
SECONDARY outcome
Timeframe: Year 1, year 2Population: The randomized or transplanted participants are included in the analyses.
Incidence of relapse/progression will be estimated using cumulative incidence function, treating death in remission as a competing risk. Relapse is defined by either morphological or cytogenetic evidence of acute leukemia consistent with pre-transplant features, or radiologic evidence of progressive lymphoma. When in doubt, the diagnosis of recurrent or progressive lymphoma should be documented by tissue biopsy. Minimal residual disease will not be considered evidence of relapse, however, minimal residual disease that progresses will be considered as relapse and the date of relapse will be the date of detection of minimal residual disease that prompted an intervention by the treating physician. Finally, institution of any therapy to treat persistent, progressive or relapsed disease, including withdrawal of immunosuppressive therapy or DLI, will be considered evidence of relapse/progression regardless of whether the criteria described above are met.
Outcome measures
| Measure |
dUCB
n=186 Participants
Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen.
Double unrelated cord blood Transplant: The conditioning regimen consists of:
* Fludarabine 40 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide 50 mg/kg IV Day -6
* Total Body Irradiation (TBI): - 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the last 3 months or an autologous transplant within 24 months of enrollment; - 300 cGY Day -1 for patients who have not received cytotoxic chemotherapy within 3 months of enrollment or an autologous transplant within 24 months of enrollment
* Day 0 will be the day of the double UCB transplant
The GVHD prophylaxis regimen consists of:
* Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL. Tacrolimus (trough level of 5-15 ng/mL) may be substituted for cyclosporine if the patient is intolerant of cyclosporine or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day-3 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
Haplo-BM
n=182 Participants
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
* Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5
* Total body irradiation (TBI) 200cGy Day -1
* Day 0 will be the day of infusion of non-T-cell depleted bone marrow
The GVHD prophylaxis regimen consists of:
* Cy 50 mg/kg IV Days 3, 4
* Tacrolimus (IV or PO) beginning Day 5 with dose adjusted to maintain a trough level of 5-15 ng/mL. Cyclosporine (trough level of 200-400 ng/mL) may be substituted for tacrolimus if the patient is intolerant of tacrolimus or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
|---|---|---|
|
Percentage of Participants With Relapse/Progression
1 Year Post Randomization
|
41.1 percentage of participants
Interval 33.9 to 48.1
|
37.6 percentage of participants
Interval 30.5 to 44.7
|
|
Percentage of Participants With Relapse/Progression
1 Year Post Transplant
|
38.7 percentage of participants
Interval 31.4 to 46.0
|
35.1 percentage of participants
Interval 27.8 to 42.5
|
|
Percentage of Participants With Relapse/Progression
2 Year Post Randomization
|
47.1 percentage of participants
Interval 39.6 to 54.2
|
48.4 percentage of participants
Interval 40.7 to 55.7
|
|
Percentage of Participants With Relapse/Progression
2 Year Post Transplant
|
43.5 percentage of participants
Interval 35.8 to 50.9
|
45.8 percentage of participants
Interval 37.7 to 53.5
|
SECONDARY outcome
Timeframe: Day 28, Day 56, Day 180, 1 year, and 2 yearsPopulation: The transplanted participants are included in the analysis. A total of 26 patients (11 on the dUCB arm and 15 on the Haplo-BM arm) who did not proceed to the study transplant are excluded.
They are all Grade ≥ 3 toxicities based on NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.
Outcome measures
| Measure |
dUCB
n=175 Participants
Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen.
Double unrelated cord blood Transplant: The conditioning regimen consists of:
* Fludarabine 40 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide 50 mg/kg IV Day -6
* Total Body Irradiation (TBI): - 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the last 3 months or an autologous transplant within 24 months of enrollment; - 300 cGY Day -1 for patients who have not received cytotoxic chemotherapy within 3 months of enrollment or an autologous transplant within 24 months of enrollment
* Day 0 will be the day of the double UCB transplant
The GVHD prophylaxis regimen consists of:
* Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL. Tacrolimus (trough level of 5-15 ng/mL) may be substituted for cyclosporine if the patient is intolerant of cyclosporine or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day-3 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
Haplo-BM
n=167 Participants
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
* Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5
* Total body irradiation (TBI) 200cGy Day -1
* Day 0 will be the day of infusion of non-T-cell depleted bone marrow
The GVHD prophylaxis regimen consists of:
* Cy 50 mg/kg IV Days 3, 4
* Tacrolimus (IV or PO) beginning Day 5 with dose adjusted to maintain a trough level of 5-15 ng/mL. Cyclosporine (trough level of 200-400 ng/mL) may be substituted for tacrolimus if the patient is intolerant of tacrolimus or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
|---|---|---|
|
Toxicities
Toxicities Reported at Day 0-28 : Somnolence
|
2 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : Bilirubin
|
8 Toxicities
|
3 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : Somnolence
|
4 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : Thrombotic Thrombocytopenic Purpura
|
6 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : Capillary Leak Syndrome
|
0 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : Hypoxia
|
6 Toxicities
|
5 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : Dyspnea
|
9 Toxicities
|
6 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : ALT
|
7 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : AST
|
5 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : Bilirubin
|
3 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : Alkaline Phosphatase
|
2 Toxicities
|
0 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : Abnormal Liver Symptoms
|
4 Toxicities
|
4 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : Received Dialysis
|
3 Toxicities
|
2 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : Seizure
|
0 Toxicities
|
0 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : Infusion Toxicities
|
0 Toxicities
|
0 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : Oral Mucositis
|
1 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : Cystitis Noninfective
|
1 Toxicities
|
2 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : Acute Kidney Injury
|
9 Toxicities
|
7 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : Chronic Kidney Disease
|
1 Toxicities
|
4 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : Hemorrhage
|
3 Toxicities
|
6 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : Hypotension
|
12 Toxicities
|
10 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : Cardiac Arrhythmia
|
4 Toxicities
|
3 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : Left Ventricular Systolic Dysfunction
|
2 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : Somnolence
|
5 Toxicities
|
2 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : Thrombotic Thrombocytopenic Purpura
|
3 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : Capillary Leak Syndrome
|
1 Toxicities
|
0 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : Hypoxia
|
22 Toxicities
|
7 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : Dyspnea
|
21 Toxicities
|
8 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : ALT
|
6 Toxicities
|
4 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : AST
|
8 Toxicities
|
5 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : Alkaline Phosphatase
|
4 Toxicities
|
4 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : Abnormal Liver Symptoms
|
6 Toxicities
|
5 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : Received Dialysis
|
2 Toxicities
|
2 Toxicities
|
|
Toxicities
Toxicities Reported at Day 57-180 : Seizure
|
0 Toxicities
|
0 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : Infusion Toxicities
|
0 Toxicities
|
0 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : Oral Mucositis
|
2 Toxicities
|
0 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : Cystitis Noninfective
|
2 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : Acute Kidney Injury
|
4 Toxicities
|
6 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : Chronic Kidney Disease
|
2 Toxicities
|
2 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : Hemorrhage
|
3 Toxicities
|
5 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : Hypotension
|
3 Toxicities
|
9 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : Cardiac Arrhythmia
|
4 Toxicities
|
5 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : Left Ventricular Systolic Dysfunction
|
2 Toxicities
|
0 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : Somnolence
|
3 Toxicities
|
5 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : Thrombotic Thrombocytopenic Purpura
|
4 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : Capillary Leak Syndrome
|
0 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : Hypoxia
|
8 Toxicities
|
10 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : Dyspnea
|
10 Toxicities
|
11 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : ALT
|
4 Toxicities
|
4 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : AST
|
5 Toxicities
|
4 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : Bilirubin
|
5 Toxicities
|
5 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : Alkaline Phosphatase
|
6 Toxicities
|
4 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : Abnormal Liver Symptoms
|
3 Toxicities
|
3 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : Received Dialysis
|
1 Toxicities
|
4 Toxicities
|
|
Toxicities
Toxicities Reported at Day 181-365 : Seizure
|
0 Toxicities
|
2 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : Infusion Toxicities
|
0 Toxicities
|
0 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : Oral Mucositis
|
3 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : Cystitis Noninfective
|
1 Toxicities
|
2 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : Acute Kidney Injury
|
3 Toxicities
|
3 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : Chronic Kidney Disease
|
1 Toxicities
|
0 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : Hemorrhage
|
2 Toxicities
|
0 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : Hypotension
|
6 Toxicities
|
5 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : Cardiac Arrhythmia
|
0 Toxicities
|
2 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : Left Ventricular Systolic Dysfunction
|
0 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : Somnolence
|
0 Toxicities
|
4 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : Thrombotic Thrombocytopenic Purpura
|
1 Toxicities
|
0 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : Capillary Leak Syndrome
|
0 Toxicities
|
0 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : Hypoxia
|
6 Toxicities
|
7 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : Dyspnea
|
4 Toxicities
|
8 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : ALT
|
1 Toxicities
|
4 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : AST
|
0 Toxicities
|
4 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : Bilirubin
|
1 Toxicities
|
3 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : Alkaline Phosphatase
|
1 Toxicities
|
3 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : Abnormal Liver Symptoms
|
2 Toxicities
|
5 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : Received Dialysis
|
1 Toxicities
|
2 Toxicities
|
|
Toxicities
Toxicities Reported at Day 363-730 : Seizure
|
0 Toxicities
|
1 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: Infusion Toxicities
|
19 Toxicities
|
7 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: Oral Mucositis
|
9 Toxicities
|
6 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: Cystitis Noninfective
|
6 Toxicities
|
6 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: Acute Kidney Injury
|
22 Toxicities
|
19 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: Chronic Kidney Disease
|
5 Toxicities
|
9 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: Hemorrhage
|
12 Toxicities
|
12 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: Hypotension
|
31 Toxicities
|
32 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: Cardiac Arrhythmia
|
14 Toxicities
|
14 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: Left Ventricular Systolic Dysfunction
|
8 Toxicities
|
3 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: Somnolence
|
13 Toxicities
|
13 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: Thrombotic Thrombocytopenic Purpura
|
14 Toxicities
|
4 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: Capillary Leak Syndrome
|
2 Toxicities
|
2 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: Hypoxia
|
41 Toxicities
|
34 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: Dyspnea
|
38 Toxicities
|
35 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: ALT
|
18 Toxicities
|
19 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: AST
|
19 Toxicities
|
18 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: Bilirubin
|
18 Toxicities
|
13 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: Alkaline Phosphatase
|
14 Toxicities
|
12 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: Abnormal Liver Symptoms
|
15 Toxicities
|
18 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: Received Dialysis
|
8 Toxicities
|
9 Toxicities
|
|
Toxicities
Overall Toxicities Reported Day 0-730: Seizure
|
0 Toxicities
|
3 Toxicities
|
|
Toxicities
Toxicities Reported at Day 0-28 : Infusion Toxicities
|
19 Toxicities
|
7 Toxicities
|
|
Toxicities
Toxicities Reported at Day 0-28 : Oral Mucositis
|
2 Toxicities
|
2 Toxicities
|
|
Toxicities
Toxicities Reported at Day 0-28 : Cystitis Noninfective
|
1 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 0-28 : Acute Kidney Injury
|
4 Toxicities
|
4 Toxicities
|
|
Toxicities
Toxicities Reported at Day 0-28 : Chronic Kidney Disease
|
0 Toxicities
|
2 Toxicities
|
|
Toxicities
Toxicities Reported at Day 0-28 : Hemorrhage
|
2 Toxicities
|
6 Toxicities
|
|
Toxicities
Toxicities Reported at Day 0-28 : Hypotension
|
12 Toxicities
|
10 Toxicities
|
|
Toxicities
Toxicities Reported at Day 0-28 : Cardiac Arrhythmia
|
6 Toxicities
|
6 Toxicities
|
|
Toxicities
Toxicities Reported at Day 0-28 : Left Ventricular Systolic Dysfunction
|
2 Toxicities
|
0 Toxicities
|
|
Toxicities
Toxicities Reported at Day 0-28 : Thrombotic Thrombocytopenic Purpura
|
3 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 0-28 : Capillary Leak Syndrome
|
1 Toxicities
|
0 Toxicities
|
|
Toxicities
Toxicities Reported at Day 0-28 : Hypoxia
|
9 Toxicities
|
9 Toxicities
|
|
Toxicities
Toxicities Reported at Day 0-28 : Dyspnea
|
7 Toxicities
|
0 Toxicities
|
|
Toxicities
Toxicities Reported at Day 0-28 : ALT
|
3 Toxicities
|
6 Toxicities
|
|
Toxicities
Toxicities Reported at Day 0-28 : AST
|
2 Toxicities
|
4 Toxicities
|
|
Toxicities
Toxicities Reported at Day 0-28 : Bilirubin
|
3 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 0-28 : Alkaline Phosphatase
|
4 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 0-28 : Abnormal Liver Symptoms
|
2 Toxicities
|
4 Toxicities
|
|
Toxicities
Toxicities Reported at Day 0-28 : Received Dialysis
|
2 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 0-28 : Seizure
|
0 Toxicities
|
0 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : Infusion Toxicities
|
0 Toxicities
|
0 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : Oral Mucositis
|
3 Toxicities
|
2 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : Cystitis Noninfective
|
2 Toxicities
|
1 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : Acute Kidney Injury
|
3 Toxicities
|
3 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : Chronic Kidney Disease
|
2 Toxicities
|
3 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : Hemorrhage
|
2 Toxicities
|
4 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : Hypotension
|
5 Toxicities
|
5 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : Cardiac Arrhythmia
|
3 Toxicities
|
2 Toxicities
|
|
Toxicities
Toxicities Reported at Day 29-56 : Left Ventricular Systolic Dysfunction
|
2 Toxicities
|
1 Toxicities
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: The transplanted participants are included in the analysis.
All Grade 2 and 3 infections will be reported. Grade 1 CMV infections through Day 56 will also be reported.
Outcome measures
| Measure |
dUCB
n=175 Participants
Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen.
Double unrelated cord blood Transplant: The conditioning regimen consists of:
* Fludarabine 40 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide 50 mg/kg IV Day -6
* Total Body Irradiation (TBI): - 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the last 3 months or an autologous transplant within 24 months of enrollment; - 300 cGY Day -1 for patients who have not received cytotoxic chemotherapy within 3 months of enrollment or an autologous transplant within 24 months of enrollment
* Day 0 will be the day of the double UCB transplant
The GVHD prophylaxis regimen consists of:
* Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL. Tacrolimus (trough level of 5-15 ng/mL) may be substituted for cyclosporine if the patient is intolerant of cyclosporine or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day-3 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
Haplo-BM
n=167 Participants
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
* Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5
* Total body irradiation (TBI) 200cGy Day -1
* Day 0 will be the day of infusion of non-T-cell depleted bone marrow
The GVHD prophylaxis regimen consists of:
* Cy 50 mg/kg IV Days 3, 4
* Tacrolimus (IV or PO) beginning Day 5 with dose adjusted to maintain a trough level of 5-15 ng/mL. Cyclosporine (trough level of 200-400 ng/mL) may be substituted for tacrolimus if the patient is intolerant of tacrolimus or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
|---|---|---|
|
Participants With Infections
# Patients with Infections
|
102 Participants
|
102 Participants
|
|
Participants With Infections
Grade 1 CMV through Day 56
|
94 Participants
|
84 Participants
|
SECONDARY outcome
Timeframe: Month 6Population: The randomized participants are included in the analysis.
Total Time Alive and Not Hospitalized within 6 Months Post Randomization
Outcome measures
| Measure |
dUCB
n=186 Participants
Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen.
Double unrelated cord blood Transplant: The conditioning regimen consists of:
* Fludarabine 40 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide 50 mg/kg IV Day -6
* Total Body Irradiation (TBI): - 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the last 3 months or an autologous transplant within 24 months of enrollment; - 300 cGY Day -1 for patients who have not received cytotoxic chemotherapy within 3 months of enrollment or an autologous transplant within 24 months of enrollment
* Day 0 will be the day of the double UCB transplant
The GVHD prophylaxis regimen consists of:
* Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL. Tacrolimus (trough level of 5-15 ng/mL) may be substituted for cyclosporine if the patient is intolerant of cyclosporine or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day-3 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
Haplo-BM
n=182 Participants
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
* Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5
* Total body irradiation (TBI) 200cGy Day -1
* Day 0 will be the day of infusion of non-T-cell depleted bone marrow
The GVHD prophylaxis regimen consists of:
* Cy 50 mg/kg IV Days 3, 4
* Tacrolimus (IV or PO) beginning Day 5 with dose adjusted to maintain a trough level of 5-15 ng/mL. Cyclosporine (trough level of 200-400 ng/mL) may be substituted for tacrolimus if the patient is intolerant of tacrolimus or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
|---|---|---|
|
Hospital Admission and Length of Stay
|
127.1 Days
Standard Deviation 48.3
|
141.2 Days
Standard Deviation 42.5
|
Adverse Events
dUCB
Serious events: 4 serious events
Other events: 1 other events
Deaths: 97 deaths
Haplo-BM
Serious events: 9 serious events
Other events: 0 other events
Deaths: 74 deaths
Serious adverse events
| Measure |
dUCB
n=186 participants at risk
Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen.
Double unrelated cord blood Transplant: The conditioning regimen consists of:
* Fludarabine 40 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide 50 mg/kg IV Day -6
* Total Body Irradiation (TBI): - 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the last 3 months or an autologous transplant within 24 months of enrollment; - 300 cGY Day -1 for patients who have not received cytotoxic chemotherapy within 3 months of enrollment or an autologous transplant within 24 months of enrollment
* Day 0 will be the day of the double UCB transplant
The GVHD prophylaxis regimen consists of:
* Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL. Tacrolimus (trough level of 5-15 ng/mL) may be substituted for cyclosporine if the patient is intolerant of cyclosporine or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day-3 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
Haplo-BM
n=182 participants at risk
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
* Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5
* Total body irradiation (TBI) 200cGy Day -1
* Day 0 will be the day of infusion of non-T-cell depleted bone marrow
The GVHD prophylaxis regimen consists of:
* Cy 50 mg/kg IV Days 3, 4
* Tacrolimus (IV or PO) beginning Day 5 with dose adjusted to maintain a trough level of 5-15 ng/mL. Cyclosporine (trough level of 200-400 ng/mL) may be substituted for tacrolimus if the patient is intolerant of tacrolimus or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
|---|---|---|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.54%
1/186 • Number of events 1 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
0.00%
0/182 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
|
Respiratory, thoracic and mediastinal disorders
Supraventricular tachycardia
|
0.00%
0/186 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
0.55%
1/182 • Number of events 1 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
|
Injury, poisoning and procedural complications
Arterial injury
|
0.54%
1/186 • Number of events 1 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
0.00%
0/182 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
0.54%
1/186 • Number of events 1 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
0.00%
0/182 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
|
Injury, poisoning and procedural complications
Vascular access complication
|
0.00%
0/186 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
0.55%
1/182 • Number of events 1 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukemia
|
0.00%
0/186 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
0.55%
1/182 • Number of events 1 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
|
Nervous system disorders
Central nervous system lesion
|
0.00%
0/186 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
0.55%
1/182 • Number of events 1 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
|
Nervous system disorders
Syncope
|
0.00%
0/186 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
0.55%
1/182 • Number of events 1 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
|
Psychiatric disorders
Psychiatric disorders Delirium
|
0.54%
1/186 • Number of events 1 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
0.00%
0/182 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/186 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
1.1%
2/182 • Number of events 2 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
|
Vascular disorders
Embolism
|
0.00%
0/186 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
0.55%
1/182 • Number of events 1 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
|
Vascular disorders
Hypotension
|
0.00%
0/186 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
0.55%
1/182 • Number of events 1 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
Other adverse events
| Measure |
dUCB
n=186 participants at risk
Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen.
Double unrelated cord blood Transplant: The conditioning regimen consists of:
* Fludarabine 40 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide 50 mg/kg IV Day -6
* Total Body Irradiation (TBI): - 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the last 3 months or an autologous transplant within 24 months of enrollment; - 300 cGY Day -1 for patients who have not received cytotoxic chemotherapy within 3 months of enrollment or an autologous transplant within 24 months of enrollment
* Day 0 will be the day of the double UCB transplant
The GVHD prophylaxis regimen consists of:
* Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL. Tacrolimus (trough level of 5-15 ng/mL) may be substituted for cyclosporine if the patient is intolerant of cyclosporine or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po TID, maximum dose 1 g po TID beginning Day-3 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
Haplo-BM
n=182 participants at risk
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
* Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2
* Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5
* Total body irradiation (TBI) 200cGy Day -1
* Day 0 will be the day of infusion of non-T-cell depleted bone marrow
The GVHD prophylaxis regimen consists of:
* Cy 50 mg/kg IV Days 3, 4
* Tacrolimus (IV or PO) beginning Day 5 with dose adjusted to maintain a trough level of 5-15 ng/mL. Cyclosporine (trough level of 200-400 ng/mL) may be substituted for tacrolimus if the patient is intolerant of tacrolimus or per institutional practice.
* Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
Supportive care includes:
\- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC \>1500/mm3 for 3 consecutive measurements on at least two different days
|
|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome
|
0.54%
1/186 • Number of events 1 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
0.00%
0/182 • Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE 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 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place