Trial Outcomes & Findings for Donor Umbilical Cord Blood Transplant With or Without Ex-vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes (NCT NCT01690520)
NCT ID: NCT01690520
Last Updated: 2021-07-06
Results Overview
First of two consecutive days with absolute neutrophil count (ANC) equal to or greater than 500 cell/microliter measured from day of transplant.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
163 participants
Primary outcome timeframe
Up to 55 days post-transplant
Results posted on
2021-07-06
Participant Flow
The Full Analysis Set includes all randomized subjects (78 in Arm I SOC and 82 in Arm II Expanded Arm). The modified intent to treat (mITT) analysis set requires subjects in the FAS to undergo hematopoietic cell transplant (HCT) and receive study drug. Two subjects in Arm II withdrew prior to receiving study drug and are therefore not included in the mITT analysis set (78 in SOC and 80 in Expanded Arm).
Participant milestones
| Measure |
Arm I (Standard of Care)
CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
Arm II (Experimental)
CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
|---|---|---|
|
Overall Study
STARTED
|
78
|
82
|
|
Overall Study
Modified Intent to Treat (mITT)
|
78
|
80
|
|
Overall Study
COMPLETED
|
27
|
35
|
|
Overall Study
NOT COMPLETED
|
51
|
47
|
Reasons for withdrawal
| Measure |
Arm I (Standard of Care)
CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
Arm II (Experimental)
CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
|---|---|---|
|
Overall Study
Death
|
25
|
21
|
|
Overall Study
Lost to Follow-up
|
2
|
3
|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
|
Overall Study
Relapse
|
0
|
1
|
|
Overall Study
Other
|
0
|
1
|
|
Overall Study
Ongoing Follow-Up at time of Analysis
|
22
|
21
|
Baseline Characteristics
Donor Umbilical Cord Blood Transplant With or Without Ex-vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes
Baseline characteristics by cohort
| Measure |
Arm I (Standard of Care)
n=78 Participants
CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
Arm II (Experimental)
n=82 Participants
CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
Total
n=160 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
27 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
51 Participants
n=5 Participants
|
58 Participants
n=7 Participants
|
109 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
26.76 Years
STANDARD_DEVIATION 14.858 • n=5 Participants
|
27.72 Years
STANDARD_DEVIATION 14.699 • n=7 Participants
|
27.25 Years
STANDARD_DEVIATION 14.738 • n=5 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
67 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
51 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
93 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
19 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
59 Participants
n=5 Participants
|
57 Participants
n=7 Participants
|
116 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
15 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
34 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
86 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
7 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
12 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
78 participants
n=5 Participants
|
82 participants
n=7 Participants
|
160 participants
n=5 Participants
|
|
Height (cm)
|
160.09 centimeters
STANDARD_DEVIATION 23.481 • n=5 Participants
|
159.85 centimeters
STANDARD_DEVIATION 24.680 • n=7 Participants
|
159.97 centimeters
STANDARD_DEVIATION 24.028 • n=5 Participants
|
|
Weight (kg)
|
67.70 kilograms
STANDARD_DEVIATION 26.886 • n=5 Participants
|
69.77 kilograms
STANDARD_DEVIATION 27.103 • n=7 Participants
|
68.76 kilograms
STANDARD_DEVIATION 26.933 • n=5 Participants
|
|
Cord Blood Units Received
1 Cord Blood Unit
|
22 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Cord Blood Units Received
2 Cord Blood Units
|
56 Participants
n=5 Participants
|
65 Participants
n=7 Participants
|
121 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 55 days post-transplantPopulation: The primary analysis set for the analysis of Neutrophil Enrgraftment and Platelet Engraftment was the modified intent to treat (mITT) analysis set. The difference between the full analysis set (FAS) and the mITT is the requirement to undergo hematopoietic cell transplant (HCT) and receive study drug. Two subjects in Arm II withdrew prior to receiving study drug, and are therefore not included in the mITT analysis set, nor the primary efficacy analyses.
First of two consecutive days with absolute neutrophil count (ANC) equal to or greater than 500 cell/microliter measured from day of transplant.
Outcome measures
| Measure |
Arm I (Standard of Care)
n=72 Participants
CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
Arm II (Experimental)
n=75 Participants
CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
|---|---|---|
|
Time to Neutrophil Engraftment
|
20.0 days
Interval 19.0 to 22.0
|
22.0 days
Interval 20.0 to 24.0
|
SECONDARY outcome
Timeframe: Up to 100 days post-transplantPopulation: The primary analysis set for the analysis of Neutrophil Enrgraftment and Platelet Engraftment was the modified intent to treat (mITT) analysis set. The difference between the full analysis set (FAS) and the mITT is the requirement to undergo hematopoietic cell transplant (HCT) and receive study drug. Two subjects in Arm II withdrew prior to receiving study drug, and are therefore not included in the mITT analysis set, nor the primary efficacy analyses.
First day of seven consecutive days with platelet count equal to or greater than 20,000 cells/microliter without platelet transfusions measured from day of transplant.
Outcome measures
| Measure |
Arm I (Standard of Care)
n=65 Participants
CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
Arm II (Experimental)
n=66 Participants
CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
|---|---|---|
|
Time to Platelet Engraftment (20k)
|
40.0 days
Interval 34.0 to 42.0
|
38.0 days
Interval 35.0 to 43.0
|
SECONDARY outcome
Timeframe: Up to 2 yearsOutcome measures
| Measure |
Arm I (Standard of Care)
n=78 Participants
CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
Arm II (Experimental)
n=80 Participants
CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
|---|---|---|
|
Overall Survival
|
52 Participants
|
57 Participants
|
SECONDARY outcome
Timeframe: Up to 2 yearsOutcome measures
| Measure |
Arm I (Standard of Care)
n=78 Participants
CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
Arm II (Experimental)
n=80 Participants
CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
|---|---|---|
|
Non-relapse Mortality
|
16 Participants
|
16 Participants
|
SECONDARY outcome
Timeframe: Up to 100 days post-transplantOutcome measures
| Measure |
Arm I (Standard of Care)
n=78 Participants
CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
Arm II (Experimental)
n=80 Participants
CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
|---|---|---|
|
Proportion of Patients With Severe Acute Graft Versus Host Disease
|
0.14 proportion of participants
Interval 0.07 to 0.24
|
0.16 proportion of participants
Interval 0.09 to 0.26
|
SECONDARY outcome
Timeframe: Up to 2 yearsOutcome measures
| Measure |
Arm I (Standard of Care)
n=78 Participants
CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
Arm II (Experimental)
n=80 Participants
CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
|---|---|---|
|
Proportion of Participants With Chronic Graft Versus Host Disease
|
27 Participants
|
23 Participants
|
Adverse Events
Arm I (Standard of Care)
Serious events: 48 serious events
Other events: 71 other events
Deaths: 25 deaths
Arm II (Experimental)
Serious events: 55 serious events
Other events: 73 other events
Deaths: 21 deaths
Serious adverse events
| Measure |
Arm I (Standard of Care)
n=78 participants at risk
CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
Arm II (Experimental)
n=82 participants at risk
CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
|---|---|---|
|
General disorders
Pyrexia
|
17.9%
14/78 • 84 days
|
20.7%
17/82 • 84 days
|
|
General disorders
Multiple organ dysfunction syndrome
|
1.3%
1/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
General disorders
Chest pain
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
General disorders
Chills
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
General disorders
Complication associated with device
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
General disorders
Death
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
General disorders
Non-cardiac chest pain
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Clostridium difficile infection
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Cytomegalovirus gastritis
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Cytomegalovirus infection
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Eye infection
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Herpes virus infection
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Klebsiella infection
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Oral infection
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Pneumonia klebsiella
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Pseudomonas infection
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Rhinovirus infection
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Sinusitis
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Skin infection
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Systemic candida
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Urinary tract infection enterococcal
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Sepsis
|
2.6%
2/78 • 84 days
|
6.1%
5/82 • 84 days
|
|
Infections and infestations
Staphylococcal infection
|
2.6%
2/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Infections and infestations
BK virus infection
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Cytomegalovirus viraemia
|
0.00%
0/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Infections and infestations
Lung infection
|
2.6%
2/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Pneumonia fungal
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Staphylococcal bacteraemia
|
0.00%
0/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.3%
1/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Organising pneumonia
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary alveolar haemorrhage
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary infarction
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary mass
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
5.1%
4/78 • 84 days
|
3.7%
3/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
5.1%
4/78 • 84 days
|
8.5%
7/82 • 84 days
|
|
Gastrointestinal disorders
Abdominal pain
|
2.6%
2/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Gastrointestinal disorders
Jejunal perforation
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Gastrointestinal disorders
Lower gastrointestinal haemorrhage
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Gastrointestinal disorders
Pneumatosis intestinalis
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Gastrointestinal disorders
Diarrhoea
|
1.3%
1/78 • 84 days
|
7.3%
6/82 • 84 days
|
|
Gastrointestinal disorders
Colitis
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Gastrointestinal disorders
Nausea
|
3.8%
3/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Gastrointestinal disorders
Vomiting
|
2.6%
2/78 • 84 days
|
3.7%
3/82 • 84 days
|
|
Immune system disorders
Acute graft versus host disease in intestine
|
1.3%
1/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Immune system disorders
Graft versus host disease in gastrointestinal tract
|
2.6%
2/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Immune system disorders
Hypersensitivity
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Immune system disorders
Acute graft versus host disease in liver
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Immune system disorders
Graft versus host disease
|
6.4%
5/78 • 84 days
|
8.5%
7/82 • 84 days
|
|
Renal and urinary disorders
Haematuria
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Renal and urinary disorders
Acute kidney injury
|
5.1%
4/78 • 84 days
|
4.9%
4/82 • 84 days
|
|
Vascular disorders
Hypertension
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Vascular disorders
Hypotension
|
5.1%
4/78 • 84 days
|
3.7%
3/82 • 84 days
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
0.00%
0/78 • 84 days
|
3.7%
3/82 • 84 days
|
|
Injury, poisoning and procedural complications
Transplant failure
|
1.3%
1/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Nervous system disorders
Haemorrhage intracranial
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Nervous system disorders
Headache
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Nervous system disorders
Neuropathy peripheral
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Nervous system disorders
Posterior reversible encephalopathy syndrome
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Nervous system disorders
Seizure
|
2.6%
2/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Cardiac disorders
Atrial flutter
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Cardiac disorders
Tachycardia
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Blood and lymphatic system disorders
Lymphatic disorder
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Investigations
Platelet count decreased
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Hepatobiliary disorders
Hepatic failure
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Metabolism and nutrition disorders
Hypokalemia
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Psychiatric disorders
Delirium
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
Other adverse events
| Measure |
Arm I (Standard of Care)
n=78 participants at risk
CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate IV over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose TBI BID on days -4 to -1 OR Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI QD on days -2 to -1.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or TID (children) or PO on days -3 to 100 with taper beginning on day 101. Patients also receive MMF IV TID a day on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin a taper if there is no evidence of GVHD and are well-engrafted from one donor unit.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
Arm II (Experimental)
n=82 participants at risk
CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm.
TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also undergo infusion of ex vivo-expanded cord blood progenitor cell infusion at least 4 hours after completion of UCB transplant.
GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm.
Cyclophosphamide: Given IV
Cyclosporine: Given IV or PO
Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion: Given IV
Fludarabine Phosphate: Given IV
Mycophenolate Mofetil: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo high dose or middle intensity TBI
Umbilical Cord Blood Transplantation: Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
|
|---|---|---|
|
Investigations
Weight increased
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Investigations
Platelet count decreased
|
16.7%
13/78 • 84 days
|
11.0%
9/82 • 84 days
|
|
Metabolism and nutrition disorders
Decreased appetite
|
50.0%
39/78 • 84 days
|
46.3%
38/82 • 84 days
|
|
Metabolism and nutrition disorders
Hypokalemia
|
17.9%
14/78 • 84 days
|
17.1%
14/82 • 84 days
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
10.3%
8/78 • 84 days
|
14.6%
12/82 • 84 days
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
11.5%
9/78 • 84 days
|
12.2%
10/82 • 84 days
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
7.7%
6/78 • 84 days
|
12.2%
10/82 • 84 days
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
3.8%
3/78 • 84 days
|
6.1%
5/82 • 84 days
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
3.8%
3/78 • 84 days
|
3.7%
3/82 • 84 days
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
2.6%
2/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Metabolism and nutrition disorders
Acidosis
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Metabolism and nutrition disorders
Hypermagnesaemia
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Metabolism and nutrition disorders
Iron overload
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Metabolism and nutrition disorders
Dehydration
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Gastrointestinal disorders
Colitis
|
9.0%
7/78 • 84 days
|
11.0%
9/82 • 84 days
|
|
Gastrointestinal disorders
Enterocolitis
|
2.6%
2/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Gastrointestinal disorders
Gastritis
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Gastrointestinal disorders
Ileus
|
2.6%
2/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Gastrointestinal disorders
Large intestinal haemorrhage
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Gastrointestinal disorders
Impaired gastric emptying
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Gastrointestinal disorders
Lower gastrointestinal haemorrhage
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Gastrointestinal disorders
Oesophagitis
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Gastrointestinal disorders
Periodontal disease
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Gastrointestinal disorders
Proctitis
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Gastrointestinal disorders
Stomatitis
|
38.5%
30/78 • 84 days
|
43.9%
36/82 • 84 days
|
|
Gastrointestinal disorders
Nausea
|
19.2%
15/78 • 84 days
|
30.5%
25/82 • 84 days
|
|
Gastrointestinal disorders
Diarrhoea
|
14.1%
11/78 • 84 days
|
13.4%
11/82 • 84 days
|
|
Gastrointestinal disorders
Vomiting
|
6.4%
5/78 • 84 days
|
11.0%
9/82 • 84 days
|
|
Gastrointestinal disorders
Abdominal pain
|
10.3%
8/78 • 84 days
|
4.9%
4/82 • 84 days
|
|
Vascular disorders
Embolism
|
0.00%
0/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Vascular disorders
Hypertension
|
55.1%
43/78 • 84 days
|
51.2%
42/82 • 84 days
|
|
Vascular disorders
Hypotension
|
9.0%
7/78 • 84 days
|
7.3%
6/82 • 84 days
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
47.4%
37/78 • 84 days
|
48.8%
40/82 • 84 days
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.8%
3/78 • 84 days
|
3.7%
3/82 • 84 days
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
2.6%
2/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Enterococcal infection
|
6.4%
5/78 • 84 days
|
3.7%
3/82 • 84 days
|
|
Infections and infestations
Adenovirus infection
|
5.1%
4/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Infections and infestations
Alpha haemolytic streptococcal infection
|
6.4%
5/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Cystitis
|
5.1%
4/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Infections and infestations
Urinary tract infection
|
3.8%
3/78 • 84 days
|
3.7%
3/82 • 84 days
|
|
Infections and infestations
BK virus infection
|
1.3%
1/78 • 84 days
|
3.7%
3/82 • 84 days
|
|
Infections and infestations
Device related infection
|
2.6%
2/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Infections and infestations
Sinusitis
|
2.6%
2/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Infections and infestations
Skin infection
|
1.3%
1/78 • 84 days
|
3.7%
3/82 • 84 days
|
|
Infections and infestations
Candida infection
|
2.6%
2/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Encephalitis
|
0.00%
0/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Infections and infestations
Escherichia infection
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Human polyomavirus infection
|
2.6%
2/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Pseudomonas infection
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Sepsis
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Stomatococcal infection
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Upper respiratory tract infection
|
2.6%
2/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Actinomycotic sepsis
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Administration site cellulitis
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Bacillus infection
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Bacteraemia
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Coronavirus infection
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Corynebacterium infection
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Cytomegalovirus colitis
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Enterobacter infection
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Enterocolitis infection
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Escherichia bacteraemia
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Fusobacterium infection
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Gastric infection
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Influenza
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Leuconostoc infection
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Lip infection
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Osteomyelitis
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Wound infection
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Infections and infestations
Staphylococcal infection
|
9.0%
7/78 • 84 days
|
6.1%
5/82 • 84 days
|
|
Infections and infestations
Lung infection
|
9.0%
7/78 • 84 days
|
7.3%
6/82 • 84 days
|
|
Infections and infestations
Human herpesvirus 6 infection
|
7.7%
6/78 • 84 days
|
6.1%
5/82 • 84 days
|
|
Infections and infestations
Cytomegalovirus infection
|
2.6%
2/78 • 84 days
|
8.5%
7/82 • 84 days
|
|
Infections and infestations
Streptococcal infection
|
9.0%
7/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Infections and infestations
Bacterial infection
|
5.1%
4/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Infections and infestations
Clostridium difficile infection
|
3.8%
3/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Investigations
Blood bilirubin increased
|
14.1%
11/78 • 84 days
|
9.8%
8/82 • 84 days
|
|
Investigations
Alanine aminotransferase increased
|
3.8%
3/78 • 84 days
|
3.7%
3/82 • 84 days
|
|
Investigations
Aspartate aminotransferase increased
|
2.6%
2/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Investigations
Blood aluminium increased
|
1.3%
1/78 • 84 days
|
3.7%
3/82 • 84 days
|
|
Investigations
Blood alkaline phosphatase increased
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Investigations
Weight decreased
|
2.6%
2/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Investigations
White blood cell count increased
|
0.00%
0/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Investigations
Electrocardiogram QT prolonged
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Investigations
Urine output decreased
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Investigations
Neutrophil count decreased
|
10.3%
8/78 • 84 days
|
3.7%
3/82 • 84 days
|
|
Investigations
White blood cell count decreased
|
5.1%
4/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Investigations
Blood creatinine increased
|
1.3%
1/78 • 84 days
|
7.3%
6/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal inflammation
|
2.6%
2/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Organising pneumonia
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Stridor
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
7.7%
6/78 • 84 days
|
7.3%
6/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.3%
1/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
10.3%
8/78 • 84 days
|
11.0%
9/82 • 84 days
|
|
Nervous system disorders
Seizure
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Nervous system disorders
Tremor
|
0.00%
0/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Nervous system disorders
Cognitive disorder
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Nervous system disorders
Dysaesthesia
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Nervous system disorders
Myoclonus
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Nervous system disorders
Somnolence
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Nervous system disorders
Headache
|
11.5%
9/78 • 84 days
|
6.1%
5/82 • 84 days
|
|
Nervous system disorders
Peripheral motor neuropathy
|
1.3%
1/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Nervous system disorders
Syncope
|
1.3%
1/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
General disorders
Fatigue
|
3.8%
3/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
General disorders
Oedema peripheral
|
0.00%
0/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
General disorders
Chills
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
General disorders
Mucosal inflammation
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
General disorders
Multiple organ dysfunction syndrome
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
General disorders
Pneumatosis
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Gastrointestinal disorders
Pain
|
10.3%
8/78 • 84 days
|
3.7%
3/82 • 84 days
|
|
Gastrointestinal disorders
Pyrexia
|
1.3%
1/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Blood and lymphatic system disorders
Haemolytic uraemic syndrome
|
3.8%
3/78 • 84 days
|
3.7%
3/82 • 84 days
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Blood and lymphatic system disorders
Thrombotic microangiopathy
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Blood and lymphatic system disorders
Thrombotic thrombocytopenic purpura
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Blood and lymphatic system disorders
Haemolysis
|
2.6%
2/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Blood and lymphatic system disorders
Anaemia
|
6.4%
5/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Renal and urinary disorders
Acute kidney injury
|
1.3%
1/78 • 84 days
|
3.7%
3/82 • 84 days
|
|
Renal and urinary disorders
Chronic kidney disease
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Renal and urinary disorders
Urinary tract pain
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Renal and urinary disorders
Haematuria
|
6.4%
5/78 • 84 days
|
4.9%
4/82 • 84 days
|
|
Psychiatric disorders
Depression
|
3.8%
3/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Psychiatric disorders
Insomnia
|
1.3%
1/78 • 84 days
|
3.7%
3/82 • 84 days
|
|
Psychiatric disorders
Anxiety
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Psychiatric disorders
Confusional state
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Psychiatric disorders
Delirium
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.8%
3/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Cardiac disorders
Pericardial effusion
|
2.6%
2/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Cardiac disorders
Cardiac failure
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Cardiac disorders
Bradycardia
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Cardiac disorders
Tachycardia
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Reproductive system and breast disorders
Menorrhagia
|
0.00%
0/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Reproductive system and breast disorders
Vulvovaginal inflammation
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
1.3%
1/78 • 84 days
|
2.4%
2/82 • 84 days
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Injury, poisoning and procedural complications
Radiation skin injury
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Injury, poisoning and procedural complications
Tracheal haemorrhage
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Endocrine disorders
Adrenal insufficiency
|
1.3%
1/78 • 84 days
|
1.2%
1/82 • 84 days
|
|
Immune system disorders
Anaphylactic reaction
|
1.3%
1/78 • 84 days
|
0.00%
0/82 • 84 days
|
|
Immune system disorders
Graft versus host disease
|
0.00%
0/78 • 84 days
|
1.2%
1/82 • 84 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place