Trial Outcomes & Findings for A Phase 2, Multicenter, Randomized, Open-label Study of MEDI-551 in Adults With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (NCT NCT01453205)
NCT ID: NCT01453205
Last Updated: 2018-03-12
Results Overview
Objective Response Rate is defined as the proportion of participants with a best response of complete response (CR) or partial response (PR) according to the International Working Group criteria. CR is defined as disappearance of all evidence of disease. PR is defined as 50 percent (%) decrease in the sum of the product of the perpendicular diameters (SPD) of up to 6 largest dominant nodal masses and greater than or equal to (\>=) 50% decrease in SPD of spleen/liver nodules.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
187 participants
Primary outcome timeframe
From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
Results posted on
2018-03-12
Participant Flow
The study was conducted from 27Feb2012 to 17Jun2016.
A total of 256 participants were screened, of which 187 participants were randomized in the study.
Participant milestones
| Measure |
Rituximab+ ICE/DHAP
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
|---|---|---|---|
|
Overall Study
STARTED
|
80
|
52
|
55
|
|
Overall Study
COMPLETED
|
0
|
0
|
1
|
|
Overall Study
NOT COMPLETED
|
80
|
52
|
54
|
Reasons for withdrawal
| Measure |
Rituximab+ ICE/DHAP
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
3
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
8
|
3
|
0
|
|
Overall Study
Death
|
24
|
22
|
18
|
|
Overall Study
Other
|
45
|
27
|
35
|
Baseline Characteristics
A Phase 2, Multicenter, Randomized, Open-label Study of MEDI-551 in Adults With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Baseline characteristics by cohort
| Measure |
Rituximab+ ICE/DHAP
n=80 Participants
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
n=52 Participants
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
n=55 Participants
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
TOTAL
n=187 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
56.4 YEARS
STANDARD_DEVIATION 12.3 • n=5 Participants
|
56.9 YEARS
STANDARD_DEVIATION 11.4 • n=7 Participants
|
55.9 YEARS
STANDARD_DEVIATION 11.6 • n=5 Participants
|
56.4 YEARS
STANDARD_DEVIATION 11.8 • n=4 Participants
|
|
Age, Customized
< 65 YEARS
|
60 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
138 Participants
n=4 Participants
|
|
Age, Customized
>= 65 YEARS
|
20 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
49 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
35 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
78 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
45 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
109 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)Population: Intent-To-Treat population included all participants who were randomized into the study.
Objective Response Rate is defined as the proportion of participants with a best response of complete response (CR) or partial response (PR) according to the International Working Group criteria. CR is defined as disappearance of all evidence of disease. PR is defined as 50 percent (%) decrease in the sum of the product of the perpendicular diameters (SPD) of up to 6 largest dominant nodal masses and greater than or equal to (\>=) 50% decrease in SPD of spleen/liver nodules.
Outcome measures
| Measure |
Rituximab+ ICE/DHAP
n=80 Participants
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
n=52 Participants
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
n=55 Participants
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
|---|---|---|---|
|
Objective Response Rate (ORR)
|
47.5 Percentage of participants
Interval 36.2 to 59.0
|
46.2 Percentage of participants
Interval 32.2 to 60.5
|
43.6 Percentage of participants
Interval 30.3 to 57.7
|
SECONDARY outcome
Timeframe: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)Population: Intent-To-Treat population included all participants who were randomized into the study.
Progression-free survival (PFS) is defined as the time from randomization until the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first according to the International Working Group criteria. PD is defined as appearance of any new lesions or \>= 50% increase in SPD of more than one node or \>= 50% increase in longest diameter of a previously identified node or \>50% increase from nadir in the SPD of any previous lesions. PFS (months) = (Date of PD/death or censoring - Date of randomization + 1) / (365.25/12).
Outcome measures
| Measure |
Rituximab+ ICE/DHAP
n=80 Participants
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
n=52 Participants
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
n=55 Participants
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
|---|---|---|---|
|
Progression-Free Survival (PFS)
|
6.1 months
Interval 0.0 to 39.2
|
6.6 months
Interval 0.0 to 31.3
|
7.7 months
Interval 0.0 to 14.8
|
SECONDARY outcome
Timeframe: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)Population: Intent-To-Treat population included all participants who were randomized into the study.
Event-Free Survival (EFS) is defined as the time from randomization until the first documentation of EFS events which include PD, initiation of alternative antitumor treatment or death due to any cause, whichever occurs first according to the International Working Group criteria. PD is defined as appearance of any new lesions or \>= 50% increase in SPD of more than one node or \>= 50% increase in longest diameter of a previously identified node or \>50% increase from nadir in the SPD of any previous lesions. EFS (months) = (Date of EFS or censoring - Date of randomization + 1) / (365.25/12).
Outcome measures
| Measure |
Rituximab+ ICE/DHAP
n=80 Participants
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
n=52 Participants
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
n=55 Participants
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
|---|---|---|---|
|
Event-Free Survival (EFS)
|
4.7 months
Interval 0.0 to 39.2
|
4.2 months
Interval 0.0 to 31.3
|
5.9 months
Interval 0.0 to 14.8
|
SECONDARY outcome
Timeframe: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)Population: Intent-To-Treat population included all participants who were randomized into the study.
Overall survival is defined as the time from randomization until death due to any cause according to the International Working Group criteria. OS (months) = (Date of death or censoring - Date of randomization + 1) / (365.25/12).
Outcome measures
| Measure |
Rituximab+ ICE/DHAP
n=80 Participants
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
n=52 Participants
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
n=55 Participants
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
|---|---|---|---|
|
Overall Survival (OS)
|
NA months
Interval 15.6 to
NA indicates data not estimable.
|
NA months
Interval 14.2 to
NA indicates data not estimable.
|
23.0 months
Interval 12.8 to
NA indicates data not estimable.
|
SECONDARY outcome
Timeframe: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)Population: Intent-To-Treat population included all participants who were randomized into the study.
Time to Progression (TTP) is defined as the time from randomization until the first documentation of PD according to the International Working Group criteria. PD is defined as appearance of any new lesions or \>= 50% increase in SPD of more than one node or \>= 50% increase in longest diameter of a previously identified node or \>50% increase from nadir in the SPD of any previous lesions. TTP (months) = (Date of PD or censoring - Date of randomization + 1) / (365.25/12).
Outcome measures
| Measure |
Rituximab+ ICE/DHAP
n=80 Participants
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
n=52 Participants
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
n=55 Participants
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
|---|---|---|---|
|
Time to Progression (TTP)
|
4.9 months
Interval 0.0 to 11.1
|
4.2 months
Interval 0.0 to 31.3
|
5.9 months
Interval 0.0 to 14.0
|
SECONDARY outcome
Timeframe: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)Population: ITT population included all participants who were randomized into the study. Here, "N" is number of participants analyzed for this outcome measure.
Time to response (TTR) is defined as the time from randomization until the first documentation of disease response according to the International Working Group criteria. Only participants who have achieved objective response (confirmed CR or confirmed PR) assessed by investigator were evaluated for TTR. CR is defined as disappearance of all evidence of disease. PR is defined as 50% decrease in the SPD of up to 6 largest dominant nodal masses and \>= 50% decrease in SPD of spleen/liver nodules. TTR (months) = (Date of first disease response - Date of randomization + 1) / (365.25/12).
Outcome measures
| Measure |
Rituximab+ ICE/DHAP
n=42 Participants
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
n=32 Participants
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
n=30 Participants
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
|---|---|---|---|
|
Time to Response (TTR)
|
1.7 months
Interval 0.9 to 3.8
|
2.3 months
Interval 1.5 to 3.4
|
2.3 months
Interval 1.6 to 6.0
|
SECONDARY outcome
Timeframe: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)Population: Intent-To-Treat population included all participants who were randomized into the study. Here, "N" is number of participants analyzed for this outcome measure.
Duration of Response (DR) is defined as time from start of first documented objective response (confirmed CR or confirmed PR) to first documented PD according to the International Working Group criteria. CR is defined as disappearance of all evidence of disease. PR is defined as 50% decrease in the SPD of up to 6 largest dominant nodal masses and \>= 50% decrease in SPD of spleen/liver nodules. PD: appearance of any new lesions or \>= 50% increase in SPD of more than one node or \>= 50% increase in longest diameter of a previously identified node or \> 50% increase from nadir in the SPD of any previous lesions. Only participants who have achieved objective response assessed by investigator were evaluated. DR calculated as (months) = (Date of PD or censoring - Date of first disease response + 1)/ (365.25/12).
Outcome measures
| Measure |
Rituximab+ ICE/DHAP
n=42 Participants
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
n=32 Participants
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
n=30 Participants
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
|---|---|---|---|
|
Duration of Response (DR)
|
NA months
Interval 4.9 to
NA indicates data not estimable.
|
7.1 months
Interval 4.1 to
NA indicates data not estimable.
|
7.9 months
Interval 4.6 to 12.2
|
SECONDARY outcome
Timeframe: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)Population: ITT population included all participants who were randomized into the study.
The best overall response was calculated, based upon the disease assessments recorded during the study visits, and summarized with the number of participants for the following categories: CR, PR, stable disease (SD), PD, and unknown. Responses were assessed according to the International Working Group criteria. CR: disappearance of all evidence of disease; PR: 50% decrease in the SPD of up to 6 largest dominant nodal masses and \>= 50% decrease in SPD of spleen/liver nodules; PD: appearance of any new lesions or \>= 50% increase in SPD of more than one node or \>= 50% increase in longest diameter of a previously identified node or \>50% increase from nadir in the SPD of any previous lesions; SD: failure to attain CR/PR or PD.
Outcome measures
| Measure |
Rituximab+ ICE/DHAP
n=80 Participants
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
n=52 Participants
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
n=55 Participants
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
|---|---|---|---|
|
Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR)
COMPLETE RESPONSE (CR)
|
20 Participants
Interval 16.0 to 35.9
|
6 Participants
Interval 4.4 to 23.4
|
12 Participants
Interval 11.8 to 35.0
|
|
Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR)
PARTIAL RESPONSE (PR)
|
18 Participants
|
18 Participants
|
12 Participants
|
|
Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR)
STABLE DISEASE (SD)
|
17 Participants
|
12 Participants
|
14 Participants
|
|
Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR)
PROGRESSIVE DISEASE (PD)
|
5 Participants
|
5 Participants
|
5 Participants
|
|
Number of Participants With Best Overall Response Assessed by Blinded Independent Central Review (BICR)
UNKNOWN
|
20 Participants
|
11 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: After the administration of the first dose of MEDI-551 (7 days before the Cycle 1) to last dose of MEDI-551 (Cycle 3 Day 1) (each cycle of 21 days)Population: All participants who were randomized into the study and received MEDI-551.
Acceptable dose for MEDI-551 was evaluated based on the benefit-risk analysis.
Outcome measures
| Measure |
Rituximab+ ICE/DHAP
n=107 Participants
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
|---|---|---|---|
|
Acceptable Dose of MEDI-551
|
4 milligram per kilogram (mg/kg)
|
—
|
—
|
SECONDARY outcome
Timeframe: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)Population: Safety population included all participants who received any study treatment.
An Adverse Event (AE) is any unfavourable and unintended signs, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. Serious adverse event (SAE) is any AE that resulted in death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, life-threatening, a congenital anomaly/birth defect, or an important medical event. TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 90 days after the end of treatment (EOT).
Outcome measures
| Measure |
Rituximab+ ICE/DHAP
n=79 Participants
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
n=52 Participants
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
n=54 Participants
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
TEAEs
|
78 Participants
|
51 Participants
|
52 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
TESAEs
|
33 Participants
|
25 Participants
|
27 Participants
|
SECONDARY outcome
Timeframe: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)Population: Safety population included all participants who received any study treatment.
An abnormal laboratory finding that was judged by the investigator to be clinically significant was reported as an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-551, or events absent at baseline that emerged after administration of MEDI-551, for the period extending to 90 days after the end of study treatment (EOT).
Outcome measures
| Measure |
Rituximab+ ICE/DHAP
n=79 Participants
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
n=52 Participants
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
n=54 Participants
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
Anaemia
|
47 Participants
|
32 Participants
|
33 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
Febrile neutropenia
|
16 Participants
|
9 Participants
|
12 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
Granulocytopenia
|
3 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
Leukopenia
|
9 Participants
|
6 Participants
|
10 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
Lymphopenia
|
4 Participants
|
2 Participants
|
3 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
Neutropenia
|
30 Participants
|
15 Participants
|
20 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
Pancytopenia
|
2 Participants
|
0 Participants
|
3 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
Thromobocytopenia
|
49 Participants
|
24 Participants
|
29 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
Activated partial thromboplastin time prolonged
|
0 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
Blood immunoglobulin g decreased
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
Blood immunoglobulin m decreased
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
Haemoglobin decreased
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
Immunoglobulins decreased
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
Lymphocyte count decreased
|
9 Participants
|
4 Participants
|
3 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
Neutrophil count decreased
|
7 Participants
|
6 Participants
|
8 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
Platelet count decreased
|
12 Participants
|
8 Participants
|
10 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
Platelet count increased
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Hematology/Coagulation Laboratory Results
White blood cell count decreased
|
6 Participants
|
5 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)Population: Safety population included all participants who received any study treatment.
An abnormal laboratory findings that was judged by the investigator to be clinically significant was reported as an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-551, or events absent at baseline that emerged after administration of MEDI-551, for the period extending to 90 days after the end of study treatment.
Outcome measures
| Measure |
Rituximab+ ICE/DHAP
n=79 Participants
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
n=52 Participants
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
n=54 Participants
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Hyperphosphataemia
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Hypocalcaemia
|
11 Participants
|
6 Participants
|
7 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Blood bicarbonate decreased
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Gamma-glutamyltransferase increased
|
9 Participants
|
3 Participants
|
3 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Urine sodium increased
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Hyperbilirubinaemia
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Hypernatraemia
|
3 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Hypertriglyerideaemia
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Hyperuricaemia
|
5 Participants
|
4 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Hypoalbuminaemia
|
3 Participants
|
4 Participants
|
3 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Hypoglycaemia
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Hypokalaemia
|
24 Participants
|
13 Participants
|
14 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Hypomagnesaemia
|
17 Participants
|
6 Participants
|
11 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Hyponatraemia
|
8 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Hypophosphataemia
|
4 Participants
|
3 Participants
|
3 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Hypoproteinaemia
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Alanine aminotransferase increased
|
7 Participants
|
2 Participants
|
4 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Aspartate aminotransferase increased
|
5 Participants
|
2 Participants
|
6 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Blood alkaline phosphatase increased
|
2 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Blood bilirubin increased
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Blood chloride increased
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Blood creatinine increased
|
10 Participants
|
5 Participants
|
7 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Blood lactate dehydrogenase increased
|
2 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Blood magnesium decreased
|
2 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Blood potassium decreased
|
2 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Blood uric acid decreased
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Blood uric acid increased
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Hepatic enzyme increased
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Protein total decreased
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Transaminases increased
|
1 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Dysuria
|
2 Participants
|
1 Participants
|
3 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Hematuria
|
2 Participants
|
3 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Glucose urine present
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Proteinuria
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Calcium deficiency
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Electrolyte imbalance
|
2 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Hypercalcaemia
|
2 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Hyperglycaemia
|
12 Participants
|
9 Participants
|
2 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Hyperkalaemia
|
2 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Chemistry Laboratory Results (Include Urinalysis)
Hypermagnesaemia
|
3 Participants
|
2 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)Population: Safety population included all participants who received any study treatment.
Vital signs included parameters such as heart rate, blood pressure, temperature, and respiratory rate. An abnormal vital signs and ECG findings that was judged by the investigator to be clinically significant was reported an AE. TEAEs were defined as events present at baseline that worsened in intensity after administration of MEDI-551, or events absent at baseline that emerged after administration of MEDI-551, for the period extending to 90 days after the end of study treatment.
Outcome measures
| Measure |
Rituximab+ ICE/DHAP
n=79 Participants
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
n=52 Participants
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
n=54 Participants
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Arrhythmia
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Atrial fibrillation
|
1 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Bradycardia
|
3 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Extrasystoles
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Palpitations
|
2 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Sinus arrhythmia
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Sinus bradycardia
|
1 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Systolic dysfunction
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Tachycardia
|
3 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Pyrexia
|
17 Participants
|
14 Participants
|
11 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Blood pressure increased
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Carbon dioxide decreased
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Electrocardiogram abnormal
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Electrocardiogram QT prolonged
|
0 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Heart rate irregular
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Weight decreased
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Weight increased
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Dyspnoea
|
11 Participants
|
7 Participants
|
8 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Dyspnoea exertional
|
0 Participants
|
3 Participants
|
1 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Hypertension
|
5 Participants
|
2 Participants
|
3 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Vital Signs and ECG Abnormalities
Hypotension
|
10 Participants
|
4 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: 7 days before the start of Cycle 1, Day 1 of each subsequent Cycle, EOT, and post EOT on Days 30, 60, 90 and 270 (up to 36 months from the randomization of last participant)Population: Safety population included all participants who received any study treatment.
A participant was considered ADA-positive across the study if they had a positive reading (titer of 50 or higher) at any time point during the study.
Outcome measures
| Measure |
Rituximab+ ICE/DHAP
n=52 Participants
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
n=54 Participants
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
|---|---|---|---|
|
Number of Participants Who Developed Detectable MEDI-551 Anti-drug Antibodies (ADA)
|
1 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day -7 Post dose, pre-dose and postdose on Day 1, post-dose on Days 4, 8, 15 of Cycle 1, pre-dose and postdose on Day 1 of Cycle 2 and Cycle 3Population: Participants who received MEDI-551 were analyzed for this end point.
The mean serum concentration of MEDI-551 were observed.
Outcome measures
| Measure |
Rituximab+ ICE/DHAP
n=52 Participants
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
n=54 Participants
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
|---|---|---|---|
|
Mean Serum Concentration of MEDI-551
Cycle 1 Day-7 Post Dose
|
47.0 mcg/mL
Standard Deviation 23.7
|
83.8 mcg/mL
Standard Deviation 21.9
|
—
|
|
Mean Serum Concentration of MEDI-551
Cycle 1 Day 1 Pre Dose
|
16.7 mcg/mL
Standard Deviation 5.81
|
33.1 mcg/mL
Standard Deviation 16.3
|
—
|
|
Mean Serum Concentration of MEDI-551
Cycle 1 Day 1 Post Dose
|
64.8 mcg/mL
Standard Deviation 26.4
|
116 mcg/mL
Standard Deviation 41.3
|
—
|
|
Mean Serum Concentration of MEDI-551
Cycle 1 Day 4
|
38.8 mcg/mL
Standard Deviation 14.6
|
71.9 mcg/mL
Standard Deviation 23.0
|
—
|
|
Mean Serum Concentration of MEDI-551
Cycle 1 Day 8
|
30.6 mcg/mL
Standard Deviation 9.69
|
69.3 mcg/mL
Standard Deviation 25.1
|
—
|
|
Mean Serum Concentration of MEDI-551
Cycle 1 Day 15
|
19.4 mcg/mL
Standard Deviation 6.19
|
44.7 mcg/mL
Standard Deviation 25.0
|
—
|
|
Mean Serum Concentration of MEDI-551
Cycle 2 Day 1 Pre Dose
|
15.0 mcg/mL
Standard Deviation 5.45
|
30.9 mcg/mL
Standard Deviation 14.3
|
—
|
|
Mean Serum Concentration of MEDI-551
Cycle 2 Day 1 Post Dose
|
52.3 mcg/mL
Standard Deviation 18.7
|
112 mcg/mL
Standard Deviation 32.6
|
—
|
|
Mean Serum Concentration of MEDI-551
Cycle 3 Day 1 Pre Dose
|
14.0 mcg/mL
Standard Deviation 6.50
|
36.4 mcg/mL
Standard Deviation 18.7
|
—
|
|
Mean Serum Concentration of MEDI-551
Cycle 3 Day 1 Post Dose
|
52.4 mcg/mL
Standard Deviation 16.9
|
116 mcg/mL
Standard Deviation 30.9
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 and EOT (Day 21 of Cycle 3 [each cycle of 21 days] or earlier cycles if treatment stopped before Cycle 3)Population: Participants who received MEDI-551 were analyzed for this end point.
Terminal elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the serum.
Outcome measures
| Measure |
Rituximab+ ICE/DHAP
n=52 Participants
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
n=54 Participants
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
|---|---|---|---|
|
Half-life (T1/2) of MEDI-551
Cycle 1
|
14.4 Day
Standard Deviation 5.09
|
16.5 Day
Standard Deviation 10.5
|
—
|
|
Half-life (T1/2) of MEDI-551
End of Treatment
|
18.9 Day
Standard Deviation 4.34
|
20.2 Day
Standard Deviation 5.73
|
—
|
Adverse Events
Rituximab+ ICE/DHAP
Serious events: 33 serious events
Other events: 78 other events
Deaths: 0 deaths
MEDI-551 2 mg/kg + ICE/DHAP
Serious events: 25 serious events
Other events: 49 other events
Deaths: 0 deaths
MEDI-551 4 mg/kg + ICE/DHAP
Serious events: 27 serious events
Other events: 52 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Rituximab+ ICE/DHAP
n=79 participants at risk
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
n=52 participants at risk
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
n=54 participants at risk
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Blood and lymphatic system disorders
Febrile bone marrow aplasia
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
13.9%
11/79 • Number of events 11 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
15.4%
8/52 • Number of events 10 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
16.7%
9/54 • Number of events 10 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Blood and lymphatic system disorders
Leukopenia
|
1.3%
1/79 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.1%
4/79 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.6%
3/54 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Blood and lymphatic system disorders
Pancytopenia
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
6.3%
5/79 • Number of events 7 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Blood and lymphatic system disorders
Thrombotic microangiopathy
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Cardiac disorders
Cardiac failure
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Ear and labyrinth disorders
Vertigo
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Gastrointestinal disorders
Gastritis
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Gastrointestinal disorders
Nausea
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Gastrointestinal disorders
Neutropenic colitis
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Gastrointestinal disorders
Obstruction gastric
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Gastrointestinal disorders
Vomiting
|
2.5%
2/79 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
General disorders
Death
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
General disorders
Fatigue
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
General disorders
General physical health deterioration
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
General disorders
Multiple organ dysfunction syndrome
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
General disorders
Pyrexia
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Bacterial sepsis
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Cellulitis
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Cystitis viral
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Device related infection
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Enterobacter sepsis
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Escherichia sepsis
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Pneumonia
|
3.8%
3/79 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Sepsis
|
3.8%
3/79 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
7.4%
4/54 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Septic shock
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Staphylococcal sepsis
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Injury, poisoning and procedural complications
Toxicity to various agents
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Investigations
Blood creatinine increased
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Investigations
White blood cell count decreased
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Tumour lysis syndrome
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Central nervous system lymphoma
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Nervous system disorders
Coma hepatic
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Nervous system disorders
Dizziness
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Nervous system disorders
Headache
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Nervous system disorders
Memory impairment
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Nervous system disorders
Seizure
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Nervous system disorders
Somnolence
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Nervous system disorders
Syncope
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Psychiatric disorders
Depression
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Psychiatric disorders
Mental status changes
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Psychiatric disorders
Suicidal ideation
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Renal and urinary disorders
Acute kidney injury
|
3.8%
3/79 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.8%
3/52 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Renal and urinary disorders
Nephropathy toxic
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Renal and urinary disorders
Renal failure
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal inflammation
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
1.3%
1/79 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Vascular disorders
Hypotension
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Vascular disorders
Thrombophlebitis
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
Other adverse events
| Measure |
Rituximab+ ICE/DHAP
n=79 participants at risk
Participants received Rituximab in combination with ifosfamide + carboplatin + etoposide (ICE) or dexamethasone + cisplatin + cytarabine (DHAP) for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). Rituximab (375 mg/m\^2) was administered intravenous (IV) on 2 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of rituximab, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of rituximab, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 2 mg/kg + ICE/DHAP
n=52 participants at risk
Participants received MEDI-551 (2 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (2 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
MEDI-551 4 mg/kg + ICE/DHAP
n=54 participants at risk
Participants received MEDI-551 (4 mg/kg) in combination with ICE or DHAP for 3 cycles (21-day cycles) and were followed until end of the study (36 months after the date of randomization for last participant, or date the sponsor stops the trial, whichever occurs first). MEDI-551 (4 mg/kg) was administered IV on 7 days before the start of Cycle 1 and on Day 1 of each cycle. After completion of MEDI-551, IV infusion of ICE as: ifosfamide 5 g/ m\^2 continuously for 24 hours with mesna on Day 2; carboplatin AUC=5 mg/mL x min (800 mg maximum) on Day 2; etoposide 100 mg/ m\^2 on Days 1, 2, and 3 in 21-day cycles. After completion of MEDI-551, IV infusion of DHAP as: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m\^2 continuously for 24 hours on Day 1; cytarabine 2 g/m\^2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
59.5%
47/79 • Number of events 113 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
61.5%
32/52 • Number of events 87 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
61.1%
33/54 • Number of events 111 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
7.6%
6/79 • Number of events 6 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.6%
3/54 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Blood and lymphatic system disorders
Granulocytopenia
|
3.8%
3/79 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Blood and lymphatic system disorders
Leukopenia
|
10.1%
8/79 • Number of events 10 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
11.5%
6/52 • Number of events 8 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
18.5%
10/54 • Number of events 31 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Blood and lymphatic system disorders
Lymphopenia
|
5.1%
4/79 • Number of events 22 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 18 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.6%
3/54 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Blood and lymphatic system disorders
Neutropenia
|
34.2%
27/79 • Number of events 50 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
28.8%
15/52 • Number of events 30 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
33.3%
18/54 • Number of events 45 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
59.5%
47/79 • Number of events 172 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
46.2%
24/52 • Number of events 71 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
51.9%
28/54 • Number of events 114 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Cardiac disorders
Atrial fibrillation
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Cardiac disorders
Bradycardia
|
3.8%
3/79 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Cardiac disorders
Sinus bradycardia
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Cardiac disorders
Tachycardia
|
3.8%
3/79 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Ear and labyrinth disorders
Tinnitus
|
5.1%
4/79 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.6%
3/54 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Eye disorders
Dry eye
|
5.1%
4/79 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Eye disorders
Vision blurred
|
2.5%
2/79 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Gastrointestinal disorders
Abdominal pain
|
5.1%
4/79 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
11.5%
6/52 • Number of events 9 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.3%
5/79 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
7.4%
4/54 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Gastrointestinal disorders
Constipation
|
29.1%
23/79 • Number of events 38 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
32.7%
17/52 • Number of events 23 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
33.3%
18/54 • Number of events 27 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Gastrointestinal disorders
Diarrhoea
|
24.1%
19/79 • Number of events 26 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
28.8%
15/52 • Number of events 17 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
24.1%
13/54 • Number of events 16 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Gastrointestinal disorders
Dry mouth
|
5.1%
4/79 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Gastrointestinal disorders
Dyspepsia
|
5.1%
4/79 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
7.6%
6/79 • Number of events 8 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
9.3%
5/54 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Gastrointestinal disorders
Haemorrhoids
|
5.1%
4/79 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Gastrointestinal disorders
Nausea
|
54.4%
43/79 • Number of events 75 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
44.2%
23/52 • Number of events 45 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
46.3%
25/54 • Number of events 42 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Gastrointestinal disorders
Oral pain
|
2.5%
2/79 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Gastrointestinal disorders
Stomatitis
|
6.3%
5/79 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Gastrointestinal disorders
Vomiting
|
32.9%
26/79 • Number of events 37 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
26.9%
14/52 • Number of events 28 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
25.9%
14/54 • Number of events 21 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
General disorders
Asthenia
|
11.4%
9/79 • Number of events 12 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
23.1%
12/52 • Number of events 21 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
20.4%
11/54 • Number of events 15 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
General disorders
Chills
|
7.6%
6/79 • Number of events 9 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
General disorders
Fatigue
|
27.8%
22/79 • Number of events 32 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
38.5%
20/52 • Number of events 33 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
27.8%
15/54 • Number of events 20 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
General disorders
Mucosal inflammation
|
8.9%
7/79 • Number of events 7 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.8%
3/52 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.6%
3/54 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
General disorders
Oedema
|
6.3%
5/79 • Number of events 6 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
General disorders
Oedema peripheral
|
12.7%
10/79 • Number of events 12 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
11.5%
6/52 • Number of events 9 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
9.3%
5/54 • Number of events 7 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
General disorders
Pyrexia
|
21.5%
17/79 • Number of events 24 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
23.1%
12/52 • Number of events 16 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
16.7%
9/54 • Number of events 10 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Oral candidiasis
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Oral herpes
|
5.1%
4/79 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Pneumonia
|
2.5%
2/79 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Rhinitis
|
2.5%
2/79 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Upper respiratory tract infection
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.8%
3/52 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Infections and infestations
Urinary tract infection
|
8.9%
7/79 • Number of events 10 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.8%
3/52 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.6%
3/54 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
13.9%
11/79 • Number of events 32 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
13.5%
7/52 • Number of events 9 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
11.1%
6/54 • Number of events 6 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Investigations
Alanine aminotransferase increased
|
8.9%
7/79 • Number of events 13 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
7.4%
4/54 • Number of events 7 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Investigations
Aspartate aminotransferase increased
|
6.3%
5/79 • Number of events 11 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
11.1%
6/54 • Number of events 13 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Investigations
Blood creatinine increased
|
12.7%
10/79 • Number of events 17 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
9.6%
5/52 • Number of events 8 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
13.0%
7/54 • Number of events 17 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Investigations
Blood lactate dehydrogenase increased
|
2.5%
2/79 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Investigations
Electrocardiogram qt prolonged
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Investigations
Gamma-glutamyltransferase increased
|
11.4%
9/79 • Number of events 15 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.8%
3/52 • Number of events 8 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.6%
3/54 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Investigations
Lymphocyte count decreased
|
11.4%
9/79 • Number of events 27 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
7.7%
4/52 • Number of events 13 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.6%
3/54 • Number of events 7 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Investigations
Neutrophil count decreased
|
8.9%
7/79 • Number of events 8 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
9.6%
5/52 • Number of events 8 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
14.8%
8/54 • Number of events 16 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Investigations
Platelet count decreased
|
15.2%
12/79 • Number of events 31 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
15.4%
8/52 • Number of events 38 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
18.5%
10/54 • Number of events 23 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Investigations
White blood cell count decreased
|
7.6%
6/79 • Number of events 13 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
7.7%
4/52 • Number of events 9 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
11.1%
6/54 • Number of events 22 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Decreased appetite
|
15.2%
12/79 • Number of events 14 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
13.5%
7/52 • Number of events 7 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
14.8%
8/54 • Number of events 11 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Dehydration
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.8%
3/52 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Fluid overload
|
2.5%
2/79 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
15.2%
12/79 • Number of events 23 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
15.4%
8/52 • Number of events 22 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
2.5%
2/79 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Hypermagnesaemia
|
3.8%
3/79 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
3.8%
3/79 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
6.3%
5/79 • Number of events 6 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
7.7%
4/52 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
3.8%
3/79 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
7.7%
4/52 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.6%
3/54 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
13.9%
11/79 • Number of events 31 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
11.5%
6/52 • Number of events 9 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
13.0%
7/54 • Number of events 8 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
30.4%
24/79 • Number of events 50 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
25.0%
13/52 • Number of events 23 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
25.9%
14/54 • Number of events 28 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
21.5%
17/79 • Number of events 37 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
11.5%
6/52 • Number of events 10 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
20.4%
11/54 • Number of events 19 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
10.1%
8/79 • Number of events 11 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
5.1%
4/79 • Number of events 10 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.8%
3/52 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.6%
3/54 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Metabolism and nutrition disorders
Tumour lysis syndrome
|
3.8%
3/79 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.1%
4/79 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
7.7%
4/52 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
15.2%
12/79 • Number of events 15 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
7.4%
4/54 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
8.9%
7/79 • Number of events 8 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
15.4%
8/52 • Number of events 9 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
13.0%
7/54 • Number of events 9 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
3.8%
3/79 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
1.3%
1/79 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
7.7%
4/52 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.6%
3/54 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
3.8%
3/79 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
7.6%
6/79 • Number of events 7 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
7.7%
4/52 • Number of events 8 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
3.8%
3/79 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.8%
3/52 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.6%
6/79 • Number of events 6 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Nervous system disorders
Dizziness
|
13.9%
11/79 • Number of events 12 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
15.4%
8/52 • Number of events 10 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
13.0%
7/54 • Number of events 9 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Nervous system disorders
Dysgeusia
|
3.8%
3/79 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
9.6%
5/52 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.6%
3/54 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Nervous system disorders
Headache
|
17.7%
14/79 • Number of events 19 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
13.5%
7/52 • Number of events 7 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
14.8%
8/54 • Number of events 10 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Nervous system disorders
Neuropathy peripheral
|
6.3%
5/79 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Nervous system disorders
Presyncope
|
3.8%
3/79 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Nervous system disorders
Syncope
|
2.5%
2/79 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Psychiatric disorders
Anxiety
|
8.9%
7/79 • Number of events 8 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
9.6%
5/52 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Psychiatric disorders
Confusional state
|
3.8%
3/79 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.6%
3/54 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Psychiatric disorders
Insomnia
|
10.1%
8/79 • Number of events 9 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
7.7%
4/52 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
14.8%
8/54 • Number of events 8 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Renal and urinary disorders
Acute kidney injury
|
1.3%
1/79 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.8%
3/52 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
7.4%
4/54 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Renal and urinary disorders
Dysuria
|
2.5%
2/79 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.6%
3/54 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Renal and urinary disorders
Haematuria
|
2.5%
2/79 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.8%
3/52 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Renal and urinary disorders
Pollakiuria
|
5.1%
4/79 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/54 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Renal and urinary disorders
Renal failure
|
3.8%
3/79 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.7%
10/79 • Number of events 12 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
17.3%
9/52 • Number of events 12 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
14.8%
8/54 • Number of events 8 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
13.9%
11/79 • Number of events 15 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
13.5%
7/52 • Number of events 11 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
13.0%
7/54 • Number of events 8 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/79 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.8%
3/52 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
6.3%
5/79 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.8%
3/52 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
2.5%
2/79 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.8%
3/52 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.6%
6/79 • Number of events 7 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
7.4%
4/54 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
6.3%
5/79 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.5%
2/79 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.7%
2/54 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
7.6%
6/79 • Number of events 6 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
7.6%
6/79 • Number of events 7 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
9.6%
5/52 • Number of events 7 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
14.8%
8/54 • Number of events 8 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
2.5%
2/79 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
7.4%
4/54 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
5.1%
4/79 • Number of events 5 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
3.8%
3/79 • Number of events 3 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/52 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
1.9%
1/54 • Number of events 1 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.8%
3/79 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
0.00%
0/52 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
11.1%
6/54 • Number of events 8 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Vascular disorders
Hypertension
|
6.3%
5/79 • Number of events 9 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
3.8%
2/52 • Number of events 2 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.6%
3/54 • Number of events 10 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
|
Vascular disorders
Hypotension
|
12.7%
10/79 • Number of events 12 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
5.8%
3/52 • Number of events 4 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
14.8%
8/54 • Number of events 9 • From treatment administration (Day 1) to 90 days after the end of study treatment (up to approximately 36 months from the randomization of last participant)
AE were reported for safety population, which included all participants who received any study treatment..
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee MedImmune has 60 days to review results communications prior to public release and may delete information that compromises on-going studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
- Publication restrictions are in place
Restriction type: OTHER