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Clinical Study With Blinatumomab in Pediatric and Adolescent Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01471782
Recruitment Status : Completed
First Posted : November 16, 2011
Results First Posted : February 8, 2017
Last Update Posted : February 8, 2017
Sponsor:
Information provided by (Responsible Party):
Amgen Research (Munich) GmbH

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Acute Lymphoblastic Leukemia
Intervention Biological: Blinatumomab
Enrollment 93
Recruitment Details The study was conducted in 26 centers in Germany, France, Italy, the Netherlands, the United Kingdom, and the United States of America. Results are reported for the primary analysis with a data cut-off date of 12 January 2015.
Pre-assignment Details

The Phase 1 part of the study comprised 2 parts:

  • a dose evaluation/escalation part in patients aged 2 to 17 years to define the recommended phase 2 dose of blinatumomab (4 arms),
  • a pharmacokinetic (PK) expansion part in patients less than 18 years.

The Phase 2 efficacy part enrolled patients at the recommended dose determined in phase 1.

Arm/Group Title Phase 1: Blinatumomab 5 µg/m²/Day Phase 1: Blinatumomab 15 µg/m²/Day Phase 1: Blinatumomab 30 µg/m²/Day Phase 1: Blinatumomab 15/30 µg/m²/Day Phase 1: Blinatumomab 5/15 µg/m²/Day Phase 2: Blinatumomab 5/15 µg/m²/Day
Hide Arm/Group Description Dose Evaluation/Escalation: Blinatumomab was administered as a continuous intravenous (cIV) infusion at a constant daily flow rate of 5 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment. Dose Evaluation/Escalation: Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment. Dose Evaluation/Escalation: Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 30 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment. Dose Evaluation/Escalation: Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day for the first week of cycle 1 and then at 30 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 30 µg/m²/day for up to five cycles of treatment. PK Expansion: Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment. Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment.
Period Title: Overall Study
Started 5 7 5 6 26 44
Completed 0 [1] 1 [1] 0 [1] 1 [1] 0 [1] 3 [1]
Not Completed 5 6 5 5 26 41
Reason Not Completed
Hematopoietic Stem Cell Transplantation             2             2             1             0             5             3
Lack of Efficacy             1             2             1             1             5             18
Adverse Event             1             1             2             2             3             1
Other             0             0             1             1             6             5
Change of Chemotherapy             1             1             0             0             1             4
Disease Relapse             0             0             0             1             2             1
Physician Decision             0             0             0             0             3             8
Withdrawal by Parent/Guardian             0             0             0             0             1             0
Death             0             0             0             0             0             1
[1]
Completed 5 cycles
Arm/Group Title Phase 1: Blinatumomab 5 µg/m²/Day Phase 1: Blinatumomab 15 µg/m²/Day Phase 1: Blinatumomab 30 µg/m²/Day Phase 1: Blinatumomab 15/30 µg/m²/Day Phase 1: Blinatumomab 5/15 µg/m²/Day Phase 2: Blinatumomab 5/15 µg/m²/Day Total
Hide Arm/Group Description Blinatumomab was administered as a continuous intravenous (cIV) infusion at a constant daily flow rate of 5 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment. Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment. Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 30 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment. Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day for the first week of cycle 1 and then at 30 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 30 µg/m²/day for up to five cycles of treatment. Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment. Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment. Total of all reporting groups
Overall Number of Baseline Participants 5 7 5 6 26 44 93
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 5 participants 7 participants 5 participants 6 participants 26 participants 44 participants 93 participants
< 2 years 0 0 0 0 8 2 10
2 - 6 years 3 5 2 4 9 11 34
7 - 17 years 2 2 3 2 9 31 49
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 7 participants 5 participants 6 participants 26 participants 44 participants 93 participants
Female
3
  60.0%
4
  57.1%
2
  40.0%
1
  16.7%
11
  42.3%
12
  27.3%
33
  35.5%
Male
2
  40.0%
3
  42.9%
3
  60.0%
5
  83.3%
15
  57.7%
32
  72.7%
60
  64.5%
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 5 participants 7 participants 5 participants 6 participants 26 participants 44 participants 93 participants
White 5 7 5 5 22 33 77
Asian 0 0 0 0 0 0 0
Black or African American 0 0 0 0 0 0 0
American Indian or Alaska native 0 0 0 0 0 0 0
Native Hawaiian or other Pacific islander 0 0 0 0 0 0 0
Other 0 0 0 1 3 5 9
Unknown 0 0 0 0 1 6 7
[1]
Measure Description: Race was not recorded for any patient from France and for two further patients.
Prior Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 5 participants 7 participants 5 participants 6 participants 26 participants 44 participants 93 participants
Yes 3 6 2 4 15 25 55
No 2 1 3 2 11 19 38
1.Primary Outcome
Title Phase I: Number of Participants With Dose-limiting Toxicities (DLTs)
Hide Description

The maximum tolerated dose (MTD) was defined as one or fewer out of 6 participants experiencing a dose limiting toxicity (DLT) or the maximum administered dose (MAD).

A dose limiting toxicity is any Grade ≥ 3 adverse event related to study drug, Grade 3 fatigue, headache, insomnia, fever, hypotension or infection were not considered dose limiting toxicities. Laboratory parameters of Grade ≥ 3 but not considered as clinically relevant and/or responding to routine medical management, thrombocytopenia, leukopenia (including neutropenia and lymphopenia), and anemia were not considered dose limiting toxicities.

Time Frame Cycle 1, 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Phase 1 dose evaluation/escalation part of the study
Arm/Group Title Phase 1: Blinatumomab 5 µg/m²/Day Phase 1: Blinatumomab 15 µg/m²/Day Phase 1: Blinatumomab 30 µg/m²/Day Phase 1: Blinatumomab 15/30 µg/m²/Day
Hide Arm/Group Description:
Blinatumomab was administered as a continuous intravenous (cIV) infusion at a constant daily flow rate of 5 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 30 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day for the first week of cycle 1 and then at 30 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 30 µg/m²/day for up to five cycles of treatment.
Overall Number of Participants Analyzed 5 7 5 6
Measure Type: Number
Unit of Measure: participants
0 1 2 1
2.Primary Outcome
Title Percentage of Participants With Complete Remission in the First Two Cycles
Hide Description

Hematological assessments were performed from bone marrow biopsy samples. All hematological assessments of bone marrow were reviewed in a central laboratory. Complete remission (CR) was defined as

  • M1 bone marrow (bone marrow blasts < 5%)
  • No evidence of circulating blasts or extra-medullary disease

Complete remission includes participants with incomplete recovery of peripheral blood counts.

Time Frame Cycles 1 and 2 (12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set includes all participants who received any infusion of blinatumomab.
Arm/Group Title Phase 1: Blinatumomab 5 µg/m²/Day Phase 1: Blinatumomab 15 µg/m²/Day Phase 1: Blinatumomab 30 µg/m²/Day Phase 1: Blinatumomab 15/30 µg/m²/Day Phase 1: Blinatumomab 5/15 µg/m²/Day Phase 2: Blinatumomab 5/15 µg/m²/Day Phase 1+2: Blinatumomab 5/15 µg/m²/Day
Hide Arm/Group Description:
Blinatumomab was administered as a continuous intravenous (cIV) infusion at a constant daily flow rate of 5 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 30 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day for the first week of cycle 1 and then at 30 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 30 µg/m²/day for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/ day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment.
Overall Number of Participants Analyzed 5 7 5 6 26 44 70
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
20.0
(0.5 to 71.6)
42.9
(9.9 to 81.6)
20.0
(0.5 to 71.6)
33.3
(4.3 to 77.7)
50.0
(29.9 to 70.1)
31.8
(18.6 to 47.6)
38.6
(27.2 to 51.0)
3.Secondary Outcome
Title Number of Participants With Adverse Events
Hide Description

The severity (or intensity) of adverse events (AEs) was assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), v4.03 and according to the following:

Grade 1 - Mild adverse event; Grade 2 - Moderate adverse event; Grade 3 - Severe and undesirable adverse event; Grade 4 - Life-threatening or disabling adverse event; Grade 5 - Death. The investigator used medical judgment to determine if there was a causal relationship (ie, related, unrelated) between an adverse event and blinatumomab.

Time Frame From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Phase 1: Blinatumomab 5 µg/m²/Day Phase 1: Blinatumomab 15 µg/m²/Day Phase 1+2: Blinatumomab 5/15 µg/m²/Day Phase 1: Blinatumomab 15/30 µg/m²/Day Phase 1: Blinatumomab 30 µg/m²/Day
Hide Arm/Group Description:
Blinatumomab was administered as a continuous intravenous (cIV) infusion at a constant daily flow rate of 5 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day for the first week of cycle 1 and then at 30 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 30 µg/m²/day for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 30 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Overall Number of Participants Analyzed 5 7 70 6 5
Measure Type: Number
Unit of Measure: participants
Any adverse event (AE) 5 7 70 6 5
Adverse event of at least CTC grade 3 4 7 61 6 5
Serious adverse event (SAEs) 4 4 39 4 3
SAE of at least grade 3 4 3 28 4 3
AE leading to interruption of study drug 0 0 10 2 2
AE leading to discontinuation of study drug 1 1 4 2 2
Adverse event leading to death 0 1 8 3 1
Treatment-related adverse event (TRAE) 5 6 59 5 5
TRAE of at least CTC grade 3 4 5 38 4 5
Treatment-related serious adverse event 3 2 15 1 2
TRAE leading to discontinuation of study drug 1 1 2 1 2
TRAE leading to death 0 0 0 1 0
4.Secondary Outcome
Title Steady State Concentration of Blinatumomab
Hide Description

Blinatumomab serum concentrations were quantified in all patients during the first 2 treatment cycles in the phase 1 part of the study only. Blinatumomab concentrations were quantified using a validated bioassay, the lower limit of quantification was 50 pg/mL. Steady state serum concentration (Css) was presumed on day 1, approximately 5 half-lives after the start of the IV infusion.

The steady state serum concentration reported is the mean of the observed concentrations collected after during cycles 1 and 2.

Time Frame Cycles 1 and 2 during the IV infusion on day 3 (at least 48 hours after start of infusion) and days 8, 15 and 22 (steady state) and day 29 at End of Infusion (EoI) and 2, 4, and 8 hours after EoI for ages ≥ 2 years.
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 1 participants with available blinatumomab concentration data
Arm/Group Title Phase 1: Blinatumomab 5 µg/m²/Day Phase 1: Blinatumomab 15 µg/m²/Day Phase 1: Blinatumomab 30 µg/m²/Day
Hide Arm/Group Description:
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 30 µg/m²/day.
Overall Number of Participants Analyzed 27 34 7
Mean (Standard Deviation)
Unit of Measure: pg/mL
Cycle 1 (N = 27, 34, 7) 162  (179) 533  (392) 1520  (1020)
Cycle 2 (N = 3, 13, 5) 456  (288) 866  (655) 1150  (701)
5.Secondary Outcome
Title Time to Hematological Relapse (Duration of Response)
Hide Description

Time to hematological relapse was measured only for participants in remission and was measured from the time the participant first achieved remission until first documented relapse or death due to disease progression. Participants without a documented relapse (hematological or extramedullary) and who did not die were censored at the time of their last bone marrow assessment or their last survival follow-up visit confirming remission. Participants who died without having reported hematological relapse or without showing any clinical sign of disease progression were censored on their date of death.

Hematological relapse is defined as the proportion of blasts in bone marrow > 25% following documented remission, or extramedullary relapse.

Time to hematological relapse was analyzed by Kaplan-Meier methods and the median observation time was calculated by the reverse Kaplan Meier method.

Time Frame Up to the data cut-off date of 12 January 2015; median observation time was 23.5 months for phase 1 and 11.5 months for phase 2.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with complete remission
Arm/Group Title Phase 1: Blinatumomab Phase 2: Blinatumomab 5/15 µg/m²/Day Phase 1+2: Blinatumomab 5/15 µg/m²/Day
Hide Arm/Group Description:
Blinatumomab was administered as a continuous intravenous (cIV) infusion at a constant daily flow rate ranging from 5 to 30 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/ day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment.
Overall Number of Participants Analyzed 21 14 27
Median (95% Confidence Interval)
Unit of Measure: months
10.3
(3.9 to 16.4)
3.4 [1] 
(1.7 to NA)
5.2
(2.3 to 16.4)
[1]
Could not be estimated due to the low number of events
6.Secondary Outcome
Title Overall Survival
Hide Description

Overall survival (OS) was measured for all participants from the first treatment of blinatumomab until death due to any cause or the date of the last follow-up. Participants who did not die were censored on the last documented visit date or the date of the last contact when the patient was last known to have been alive. For patients who withdrew their informed consent only information until the date of withdrawal was analyzed.

Overall survival was estimated using Kaplan-Meier methods. The median follow-up time with respect to overall survival was calculated by the reverse Kaplan-Meier method.

Time Frame Up to the data cut-off date of 12 January 2015; median observation time was 23.5 months for phase 1 and 11.6 months for phase 2.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Phase 1: Blinatumomab Phase 2: Blinatumomab 5/15 µg/m²/Day Phase 1+2: Blinatumomab 5/15 µg/m²/Day
Hide Arm/Group Description:
Blinatumomab was administered as a continuous intravenous (cIV) infusion at a constant daily flow rate ranging from 5 to 30 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/ day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment.
Overall Number of Participants Analyzed 49 44 70
Median (95% Confidence Interval)
Unit of Measure: months
6.5
(3.6 to 10.6)
8.2
(4.0 to 14.6)
7.5
(4.0 to 11.8)
7.Secondary Outcome
Title Relapse-free Survival
Hide Description

Relapse-free survival (RFS) was assessed for participants who achieved a complete remission during the core study and was measured from the time the participant first achieved remission until first documented relapse or death due to any cause. Participants without a documented relapse (hematological or extramedullary) or who did not die were censored at the time of their last bone marrow assessment or their last survival follow-up visit confirming remission.

Relapse free survival was estimated using Kaplan-Meier methods and the median observation time was calculated by the reverse Kaplan-Meier method.

Time Frame Up to the data cut-off date of 12 January 2015; median observation time was 23.5 months for phase 1 and 11.5 months for phase 2.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set with complete remission
Arm/Group Title Phase 1: Blinatumomab Phase 2: Blinatumomab 5/15 µg/m²/Day Phase 1+2: Blinatumomab 5/15 µg/m²/Day
Hide Arm/Group Description:
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate ranging from 5 to 30 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/ day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment.
Overall Number of Participants Analyzed 21 14 27
Median (95% Confidence Interval)
Unit of Measure: months
7.9
(3.0 to 12.4)
3.4
(1.7 to 13.9)
4.4
(2.3 to 12.1)
8.Secondary Outcome
Title Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant During Blinatumomab Induced Remission
Hide Description The percentage of participants who received allogeneic hematopoietic stem cell transplantation (HSCT) while in remission due to treatment with blinatumomab during the first two cycles, and received no further anti-leukemic medication before HSCT.
Time Frame Up to the data cut-off date of 12 January 2015; Maximum duration on study was 24 months in phase 1 and 15 months for phase 2.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Phase 1: Blinatumomab 5 µg/m²/Day Phase 1: Blinatumomab 15 µg/m²/Day Phase 1: Blinatumomab 30 µg/m²/Day Phase 1: Blinatumomab 15/30 µg/m²/Day Phase 1: Blinatumomab 5/15 µg/m²/Day Phase 2: Blinatumomab 5/15 µg/m²/Day Phase 1+2: Blinatumomab 5/15 µg/m²/Day
Hide Arm/Group Description:
Blinatumomab was administered as a continuous intravenous (cIV) infusion at a constant daily flow rate of 5 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 30 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day for the first week of cycle 1 and then at 30 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 30 µg/m²/day for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/ day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment.
Overall Number of Participants Analyzed 5 7 5 6 26 44 70
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
20.0
(0.5 to 71.6)
28.6
(3.7 to 71.0)
20.0
(0.5 to 71.6)
16.7
(0.4 to 64.1)
30.8
(14.3 to 51.8)
11.4
(3.8 to 24.6)
18.6
(10.3 to 29.7)
9.Secondary Outcome
Title Number of Participants Who Developed Anti-blinatumomab Antibodies
Hide Description Antibodies to blinatumomab were detected using an electrochemiluminescence (ECL)-based assay.
Time Frame Predose up until 30 days after last dose of study medication; median treatment duration was 28 days.
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Hide Analysis Population Description
Full analysis set
Arm/Group Title Phase 1: Blinatumomab 5 µg/m²/Day Phase 1: Blinatumomab 15 µg/m²/Day Phase 1: Blinatumomab 30 µg/m²/Day Phase 1: Blinatumomab 15/30 µg/m²/Day Phase 1: Blinatumomab 5/15 µg/m²/Day Phase 2: Blinatumomab 5/15 µg/m²/Day
Hide Arm/Group Description:
Blinatumomab was administered as a continuous intravenous (cIV) infusion at a constant daily flow rate of 5 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 30 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day for the first week of cycle 1 and then at 30 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 30 µg/m²/day for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment.
Overall Number of Participants Analyzed 5 7 5 6 26 44
Measure Type: Number
Unit of Measure: participants
0 0 0 0 0 0
10.Secondary Outcome
Title Serum Cytokine Peak Levels
Hide Description The activation of immune effector cells was monitored by the measurement of peripheral blood cytokine levels including interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-alpha (TNF-α) and interferon gamma (IFN-ɣ) using cytometric bead assays. The limit of detection of the assay (LOD) was 20 pg/mL and the lower limit of quantification (LLOQ) was 125 pg/mL. Data below LOD were set to 10 pg/mL while data < LOQ and > LOD were reported as measured.
Time Frame Cycle 1 and 2 day 1 (prior to infusion, 2 and 6 hours after infusion start), day 2 and day 3.
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Phase 1 full analysis set participants with available data
Arm/Group Title Phase 1: Blinatumomab 5 µg/m²/Day Phase 1: Blinatumomab 15 µg/m²/Day Phase 1: Blinatumomab 30 µg/m²/Day
Hide Arm/Group Description:
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day..
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day.
Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 30 µg/m²/day.
Overall Number of Participants Analyzed 31 14 5
Mean (Standard Deviation)
Unit of Measure: pg/mL
IL-6: Cycle 1 Week 1 (N=31, 13, 5) 4970  (17000) 1780  (2620) 23400  (24100)
IL-6: Cycle 2 Week 1 (N=4, 14, 5) 526  (844) 892  (2370) 40.4  (68.0)
IL-10: Cycle 1 Week 1 (N=31, 13, 5) 562  (710) 1400  (2030) 3170  (1720)
IL-10: Cycle 2 Week 1 (N=4, 14, 5) 519  (497) 432  (692) 277  (308)
IFN-ɣ: Cycle 1 Week 1 (N=31, 13, 5) 207  (516) 539  (1240) 2260  (1540)
IFN-ɣ: Cycle 2 Week 1 (N=4, 14, 5) 51.8  (65.6) 47.6  (51.5) 22.8  (28.6)
IL-2: Cycle 1 Week 1 (N=31, 13, 5) 22.7  (23) 93.9  (150) 900  (1390)
IL-2: Cycle 2 Week 1 (N=4, 14, 5) 10.0  (0.00) 14.3  (8.84) 10.0  (0.00)
TNF-α: Cycle 1 Week 1 (N=31, 13, 5) 87.3  (241) 60.2  (127) 285  (306)
TNF-α: Cycle 2 Week 1 (N=4, 14, 5) 10.0  (0.00) 10.0  (0.00) 10.0  (0.00)
IL-4: Cycle 1 Week 1 (N=0, 0, 0) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
IL-4: Cycle 2 Week 1 (N=0, 0, 0) NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
[1]
Serum IL-4 levels were below detection limit (< 20 pg/mL) in all participants studied.
Time Frame From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle, median treatment duration was 28 days.
Adverse Event Reporting Description Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
 
Arm/Group Title Phase 1: Blinatumomab 5 µg/m²/Day Phase 1: Blinatumomab 15 µg/m²/Day Phase 1+2: Blinatumomab 5/15 µg/m²/Day Phase 1: Blinatumomab 15/30 µg/m²/Day Phase 1: Blinatumomab 30 µg/m²/Day Total
Hide Arm/Group Description Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment. Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment. Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 5 µg/m²/day for the first week of cycle 1 and then at 15 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 15 µg/m²/day for up to five cycles of treatment. Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 15 µg/m²/day for the first week of cycle 1 and then at 30 µg/m²/day for 3 weeks followed by a treatment-free interval of 2 weeks. Participants received subsequent cycles at 30 µg/m²/day for up to five cycles of treatment. Blinatumomab was administered as a continuous intravenous infusion at a constant daily flow rate of 30 µg/m²/day over 4 weeks followed by a treatment-free interval of 2 weeks for up to five cycles of treatment. All Participants who received blinatumomab administered as a continuous intravenous infusion at a constant daily flow rate.
All-Cause Mortality
Phase 1: Blinatumomab 5 µg/m²/Day Phase 1: Blinatumomab 15 µg/m²/Day Phase 1+2: Blinatumomab 5/15 µg/m²/Day Phase 1: Blinatumomab 15/30 µg/m²/Day Phase 1: Blinatumomab 30 µg/m²/Day Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Phase 1: Blinatumomab 5 µg/m²/Day Phase 1: Blinatumomab 15 µg/m²/Day Phase 1+2: Blinatumomab 5/15 µg/m²/Day Phase 1: Blinatumomab 15/30 µg/m²/Day Phase 1: Blinatumomab 30 µg/m²/Day Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/5 (80.00%)   4/7 (57.14%)   39/70 (55.71%)   4/6 (66.67%)   3/5 (60.00%)   54/93 (58.06%) 
Blood and lymphatic system disorders             
Disseminated intravascular coagulation  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Febrile neutropenia  1  0/5 (0.00%)  0/7 (0.00%)  8/70 (11.43%)  0/6 (0.00%)  0/5 (0.00%)  8/93 (8.60%) 
Histiocytosis haematophagic  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  1/5 (20.00%)  2/93 (2.15%) 
Thrombocytopenia  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Cardiac disorders             
Cardiac arrest  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Cardiac failure  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/93 (1.08%) 
Gastrointestinal disorders             
Colitis  1  1/5 (20.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  2/93 (2.15%) 
Mouth haemorrhage  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Oesophageal pain  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Vomiting  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
General disorders             
Death  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Device malfunction  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Disease progression  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  1/6 (16.67%)  0/5 (0.00%)  2/93 (2.15%) 
Influenza like illness  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Multi-organ failure  1  0/5 (0.00%)  0/7 (0.00%)  2/70 (2.86%)  0/6 (0.00%)  0/5 (0.00%)  2/93 (2.15%) 
Pyrexia  1  2/5 (40.00%)  1/7 (14.29%)  8/70 (11.43%)  0/6 (0.00%)  0/5 (0.00%)  11/93 (11.83%) 
Hepatobiliary disorders             
Hepatic failure  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Immune system disorders             
Cytokine release syndrome  1  0/5 (0.00%)  1/7 (14.29%)  4/70 (5.71%)  0/6 (0.00%)  2/5 (40.00%)  7/93 (7.53%) 
Drug hypersensitivity  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Infections and infestations             
Appendicitis  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Bacteraemia  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Bronchopneumonia  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Bronchopulmonary aspergillosis  1  0/5 (0.00%)  1/7 (14.29%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  2/93 (2.15%) 
Cytomegalovirus infection  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Device related infection  1  0/5 (0.00%)  0/7 (0.00%)  3/70 (4.29%)  0/6 (0.00%)  0/5 (0.00%)  3/93 (3.23%) 
Fungal infection  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Gastroenteritis viral  1  1/5 (20.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Infection  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  1/6 (16.67%)  0/5 (0.00%)  2/93 (2.15%) 
Periorbital cellulitis  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Pneumonia  1  0/5 (0.00%)  0/7 (0.00%)  2/70 (2.86%)  0/6 (0.00%)  0/5 (0.00%)  2/93 (2.15%) 
Rectal abscess  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Sepsis  1  0/5 (0.00%)  0/7 (0.00%)  3/70 (4.29%)  1/6 (16.67%)  0/5 (0.00%)  4/93 (4.30%) 
Sinusitis  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Urinary tract infection  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Injury, poisoning and procedural complications             
Overdose  1  1/5 (20.00%)  0/7 (0.00%)  3/70 (4.29%)  0/6 (0.00%)  0/5 (0.00%)  4/93 (4.30%) 
Spinal compression fracture  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Vascular access complication  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Investigations             
Enterococcus test positive  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Escherichia test positive  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Staphylococcus test positive  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Stenotrophomonas test positive  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Metabolism and nutrition disorders             
Hypertriglyceridaemia  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Tumour lysis syndrome  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/93 (1.08%) 
Musculoskeletal and connective tissue disorders             
Back pain  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Bone pain  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Muscular weakness  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Leukaemia recurrent  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Nervous system disorders             
Atonic seizures  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Convulsion  1  1/5 (20.00%)  0/7 (0.00%)  2/70 (2.86%)  0/6 (0.00%)  0/5 (0.00%)  3/93 (3.23%) 
Haemorrhage intracranial  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Headache  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Hypotonia  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Neuralgia  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Psychiatric disorders             
Confusional state  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Renal and urinary disorders             
Renal failure acute  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Reproductive system and breast disorders             
Acquired phimosis  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Respiratory, thoracic and mediastinal disorders             
Atelectasis  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Cough  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Dyspnoea  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Epistaxis  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Hypoxia  1  0/5 (0.00%)  0/7 (0.00%)  2/70 (2.86%)  0/6 (0.00%)  1/5 (20.00%)  3/93 (3.23%) 
Pleural effusion  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Pneumonitis  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Respiratory failure  1  0/5 (0.00%)  2/7 (28.57%)  2/70 (2.86%)  1/6 (16.67%)  1/5 (20.00%)  6/93 (6.45%) 
Surgical and medical procedures             
Tooth extraction  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Vascular disorders             
Capillary leak syndrome  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  2/93 (2.15%) 
Haemorrhage  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Hypertension  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Hypotension  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase 1: Blinatumomab 5 µg/m²/Day Phase 1: Blinatumomab 15 µg/m²/Day Phase 1+2: Blinatumomab 5/15 µg/m²/Day Phase 1: Blinatumomab 15/30 µg/m²/Day Phase 1: Blinatumomab 30 µg/m²/Day Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/5 (100.00%)   7/7 (100.00%)   70/70 (100.00%)   6/6 (100.00%)   5/5 (100.00%)   93/93 (100.00%) 
Blood and lymphatic system disorders             
Anaemia  1  3/5 (60.00%)  2/7 (28.57%)  29/70 (41.43%)  2/6 (33.33%)  4/5 (80.00%)  40/93 (43.01%) 
Bone marrow failure  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Coagulopathy  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/93 (1.08%) 
Disseminated intravascular coagulation  1  1/5 (20.00%)  2/7 (28.57%)  3/70 (4.29%)  1/6 (16.67%)  1/5 (20.00%)  8/93 (8.60%) 
Febrile neutropenia  1  0/5 (0.00%)  0/7 (0.00%)  8/70 (11.43%)  1/6 (16.67%)  0/5 (0.00%)  9/93 (9.68%) 
Hypoglobulinaemia  1  1/5 (20.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  2/93 (2.15%) 
Leukopenia  1  0/5 (0.00%)  2/7 (28.57%)  9/70 (12.86%)  1/6 (16.67%)  2/5 (40.00%)  14/93 (15.05%) 
Lymphopenia  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  1/5 (20.00%)  2/93 (2.15%) 
Neutropenia  1  0/5 (0.00%)  1/7 (14.29%)  12/70 (17.14%)  0/6 (0.00%)  0/5 (0.00%)  13/93 (13.98%) 
Thrombocytopenia  1  2/5 (40.00%)  2/7 (28.57%)  14/70 (20.00%)  1/6 (16.67%)  2/5 (40.00%)  21/93 (22.58%) 
Cardiac disorders             
Pericardial effusion  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Sinus bradycardia  1  0/5 (0.00%)  0/7 (0.00%)  3/70 (4.29%)  1/6 (16.67%)  2/5 (40.00%)  6/93 (6.45%) 
Sinus tachycardia  1  0/5 (0.00%)  0/7 (0.00%)  5/70 (7.14%)  1/6 (16.67%)  1/5 (20.00%)  7/93 (7.53%) 
Tachycardia  1  0/5 (0.00%)  0/7 (0.00%)  3/70 (4.29%)  0/6 (0.00%)  1/5 (20.00%)  4/93 (4.30%) 
Ear and labyrinth disorders             
Ear pain  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  1/5 (20.00%)  2/93 (2.15%) 
Endocrine disorders             
Adrenal insufficiency  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/93 (1.08%) 
Cushingoid  1  0/5 (0.00%)  0/7 (0.00%)  2/70 (2.86%)  0/6 (0.00%)  1/5 (20.00%)  3/93 (3.23%) 
Eye disorders             
Eyelid haematoma  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Eyelid oedema  1  0/5 (0.00%)  1/7 (14.29%)  2/70 (2.86%)  0/6 (0.00%)  0/5 (0.00%)  3/93 (3.23%) 
Ocular icterus  1  0/5 (0.00%)  1/7 (14.29%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  2/93 (2.15%) 
Photophobia  1  0/5 (0.00%)  1/7 (14.29%)  2/70 (2.86%)  0/6 (0.00%)  1/5 (20.00%)  4/93 (4.30%) 
Vision blurred  1  1/5 (20.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Gastrointestinal disorders             
Abdominal distension  1  0/5 (0.00%)  0/7 (0.00%)  2/70 (2.86%)  0/6 (0.00%)  1/5 (20.00%)  3/93 (3.23%) 
Abdominal pain  1  3/5 (60.00%)  3/7 (42.86%)  13/70 (18.57%)  0/6 (0.00%)  1/5 (20.00%)  20/93 (21.51%) 
Abdominal pain upper  1  1/5 (20.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Ascites  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  1/5 (20.00%)  2/93 (2.15%) 
Constipation  1  0/5 (0.00%)  0/7 (0.00%)  6/70 (8.57%)  2/6 (33.33%)  0/5 (0.00%)  8/93 (8.60%) 
Diarrhoea  1  2/5 (40.00%)  2/7 (28.57%)  9/70 (12.86%)  0/6 (0.00%)  1/5 (20.00%)  14/93 (15.05%) 
Dyspepsia  1  0/5 (0.00%)  0/7 (0.00%)  2/70 (2.86%)  1/6 (16.67%)  0/5 (0.00%)  3/93 (3.23%) 
Glossodynia  1  1/5 (20.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Ileus  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  1/6 (16.67%)  0/5 (0.00%)  2/93 (2.15%) 
Mouth haemorrhage  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  2/5 (40.00%)  2/93 (2.15%) 
Nausea  1  2/5 (40.00%)  1/7 (14.29%)  23/70 (32.86%)  1/6 (16.67%)  1/5 (20.00%)  28/93 (30.11%) 
Stomatitis  1  0/5 (0.00%)  0/7 (0.00%)  5/70 (7.14%)  0/6 (0.00%)  0/5 (0.00%)  5/93 (5.38%) 
Vomiting  1  2/5 (40.00%)  2/7 (28.57%)  17/70 (24.29%)  2/6 (33.33%)  2/5 (40.00%)  25/93 (26.88%) 
General disorders             
Adverse drug reaction  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Application site scab  1  1/5 (20.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Catheter site haematoma  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/93 (1.08%) 
Chest pain  1  1/5 (20.00%)  0/7 (0.00%)  2/70 (2.86%)  0/6 (0.00%)  0/5 (0.00%)  3/93 (3.23%) 
Chills  1  0/5 (0.00%)  0/7 (0.00%)  3/70 (4.29%)  0/6 (0.00%)  1/5 (20.00%)  4/93 (4.30%) 
Face oedema  1  1/5 (20.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  1/5 (20.00%)  3/93 (3.23%) 
Facial pain  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Fatigue  1  2/5 (40.00%)  2/7 (28.57%)  5/70 (7.14%)  0/6 (0.00%)  2/5 (40.00%)  11/93 (11.83%) 
Injection site erythema  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Injection site haematoma  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Localised oedema  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  1/5 (20.00%)  2/93 (2.15%) 
Non-cardiac chest pain  1  0/5 (0.00%)  0/7 (0.00%)  4/70 (5.71%)  0/6 (0.00%)  0/5 (0.00%)  4/93 (4.30%) 
Oedema  1  0/5 (0.00%)  0/7 (0.00%)  3/70 (4.29%)  2/6 (33.33%)  0/5 (0.00%)  5/93 (5.38%) 
Oedema peripheral  1  1/5 (20.00%)  0/7 (0.00%)  5/70 (7.14%)  0/6 (0.00%)  1/5 (20.00%)  7/93 (7.53%) 
Pain  1  1/5 (20.00%)  2/7 (28.57%)  6/70 (8.57%)  3/6 (50.00%)  0/5 (0.00%)  12/93 (12.90%) 
Pyrexia  1  4/5 (80.00%)  7/7 (100.00%)  54/70 (77.14%)  4/6 (66.67%)  5/5 (100.00%)  74/93 (79.57%) 
Hepatobiliary disorders             
Cholestasis  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Hepatic failure  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Hepatosplenomegaly  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  1/6 (16.67%)  0/5 (0.00%)  2/93 (2.15%) 
Hepatotoxicity  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  2/93 (2.15%) 
Immune system disorders             
Cytokine release syndrome  1  1/5 (20.00%)  0/7 (0.00%)  4/70 (5.71%)  2/6 (33.33%)  2/5 (40.00%)  9/93 (9.68%) 
Drug hypersensitivity  1  0/5 (0.00%)  1/7 (14.29%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  2/93 (2.15%) 
Infections and infestations             
Adenovirus infection  1  1/5 (20.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  2/93 (2.15%) 
BK virus infection  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Conjunctivitis  1  0/5 (0.00%)  1/7 (14.29%)  2/70 (2.86%)  0/6 (0.00%)  1/5 (20.00%)  4/93 (4.30%) 
Device related infection  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Enterocolitis infectious  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Legionella infection  1  1/5 (20.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Lung infection  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Nasopharyngitis  1  1/5 (20.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  2/93 (2.15%) 
Oral herpes  1  0/5 (0.00%)  1/7 (14.29%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  2/93 (2.15%) 
Polyomavirus-associated nephropathy  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Rhinitis  1  0/5 (0.00%)  0/7 (0.00%)  7/70 (10.00%)  0/6 (0.00%)  0/5 (0.00%)  7/93 (7.53%) 
Rhinovirus infection  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  1/6 (16.67%)  0/5 (0.00%)  2/93 (2.15%) 
Staphylococcal infection  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Staphylococcal sepsis  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Viral myositis  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Injury, poisoning and procedural complications             
Contusion  1  0/5 (0.00%)  0/7 (0.00%)  2/70 (2.86%)  0/6 (0.00%)  1/5 (20.00%)  3/93 (3.23%) 
Ear abrasion  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/93 (1.08%) 
Fall  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  1/5 (20.00%)  2/93 (2.15%) 
Infusion related reaction  1  0/5 (0.00%)  1/7 (14.29%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  2/93 (2.15%) 
Skin abrasion  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/93 (1.08%) 
Investigations             
Activated partial thromboplastin time prolonged  1  0/5 (0.00%)  1/7 (14.29%)  4/70 (5.71%)  0/6 (0.00%)  0/5 (0.00%)  5/93 (5.38%) 
Alanine aminotransferase increased  1  1/5 (20.00%)  0/7 (0.00%)  13/70 (18.57%)  2/6 (33.33%)  2/5 (40.00%)  18/93 (19.35%) 
Aspartate aminotransferase increased  1  1/5 (20.00%)  1/7 (14.29%)  10/70 (14.29%)  2/6 (33.33%)  2/5 (40.00%)  16/93 (17.20%) 
Blood alkaline phosphatase increased  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  1/5 (20.00%)  2/93 (2.15%) 
Blood bilirubin increased  1  0/5 (0.00%)  1/7 (14.29%)  4/70 (5.71%)  1/6 (16.67%)  3/5 (60.00%)  9/93 (9.68%) 
Blood creatinine increased  1  0/5 (0.00%)  0/7 (0.00%)  2/70 (2.86%)  0/6 (0.00%)  2/5 (40.00%)  4/93 (4.30%) 
Blood fibrinogen decreased  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  1/5 (20.00%)  2/93 (2.15%) 
Blood fibrinogen increased  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Blood immunoglobulin A decreased  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Blood immunoglobulin G decreased  1  0/5 (0.00%)  4/7 (57.14%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  5/93 (5.38%) 
Blood immunoglobulin M decreased  1  0/5 (0.00%)  1/7 (14.29%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  2/93 (2.15%) 
Blood lactate dehydrogenase increased  1  0/5 (0.00%)  1/7 (14.29%)  7/70 (10.00%)  0/6 (0.00%)  2/5 (40.00%)  10/93 (10.75%) 
C-reactive protein increased  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Cytomegalovirus test positive  1  0/5 (0.00%)  1/7 (14.29%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  2/93 (2.15%) 
Electroencephalogram abnormal  1  1/5 (20.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Fibrin D dimer increased  1  0/5 (0.00%)  2/7 (28.57%)  6/70 (8.57%)  1/6 (16.67%)  1/5 (20.00%)  10/93 (10.75%) 
Haemoglobin decreased  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
International normalised ratio increased  1  1/5 (20.00%)  2/7 (28.57%)  3/70 (4.29%)  2/6 (33.33%)  0/5 (0.00%)  8/93 (8.60%) 
Lymphocyte count decreased  1  0/5 (0.00%)  0/7 (0.00%)  3/70 (4.29%)  1/6 (16.67%)  1/5 (20.00%)  5/93 (5.38%) 
Neutrophil count decreased  1  0/5 (0.00%)  0/7 (0.00%)  9/70 (12.86%)  3/6 (50.00%)  2/5 (40.00%)  14/93 (15.05%) 
Platelet count decreased  1  0/5 (0.00%)  0/7 (0.00%)  10/70 (14.29%)  2/6 (33.33%)  1/5 (20.00%)  13/93 (13.98%) 
Protein total decreased  1  0/5 (0.00%)  0/7 (0.00%)  2/70 (2.86%)  1/6 (16.67%)  0/5 (0.00%)  3/93 (3.23%) 
Roseolovirus test positive  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Urine output decreased  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Weight decreased  1  0/5 (0.00%)  0/7 (0.00%)  4/70 (5.71%)  1/6 (16.67%)  0/5 (0.00%)  5/93 (5.38%) 
Weight increased  1  0/5 (0.00%)  1/7 (14.29%)  12/70 (17.14%)  2/6 (33.33%)  1/5 (20.00%)  16/93 (17.20%) 
White blood cell count decreased  1  0/5 (0.00%)  0/7 (0.00%)  8/70 (11.43%)  3/6 (50.00%)  2/5 (40.00%)  13/93 (13.98%) 
Metabolism and nutrition disorders             
Acidosis  1  0/5 (0.00%)  1/7 (14.29%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  2/93 (2.15%) 
Decreased appetite  1  0/5 (0.00%)  0/7 (0.00%)  3/70 (4.29%)  0/6 (0.00%)  1/5 (20.00%)  4/93 (4.30%) 
Dehydration  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  1/5 (20.00%)  2/93 (2.15%) 
Hyperglycaemia  1  0/5 (0.00%)  0/7 (0.00%)  6/70 (8.57%)  1/6 (16.67%)  0/5 (0.00%)  7/93 (7.53%) 
Hyperkalaemia  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Hypernatraemia  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Hyperphosphataemia  1  0/5 (0.00%)  2/7 (28.57%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  2/93 (2.15%) 
Hyperuricaemia  1  0/5 (0.00%)  1/7 (14.29%)  2/70 (2.86%)  0/6 (0.00%)  0/5 (0.00%)  3/93 (3.23%) 
Hypoalbuminaemia  1  0/5 (0.00%)  2/7 (28.57%)  4/70 (5.71%)  2/6 (33.33%)  0/5 (0.00%)  8/93 (8.60%) 
Hypocalcaemia  1  0/5 (0.00%)  1/7 (14.29%)  8/70 (11.43%)  1/6 (16.67%)  1/5 (20.00%)  11/93 (11.83%) 
Hypokalaemia  1  0/5 (0.00%)  4/7 (57.14%)  15/70 (21.43%)  3/6 (50.00%)  0/5 (0.00%)  22/93 (23.66%) 
Hypomagnesaemia  1  0/5 (0.00%)  0/7 (0.00%)  6/70 (8.57%)  1/6 (16.67%)  0/5 (0.00%)  7/93 (7.53%) 
Hyponatraemia  1  0/5 (0.00%)  0/7 (0.00%)  5/70 (7.14%)  2/6 (33.33%)  0/5 (0.00%)  7/93 (7.53%) 
Hypophosphataemia  1  0/5 (0.00%)  0/7 (0.00%)  10/70 (14.29%)  2/6 (33.33%)  0/5 (0.00%)  12/93 (12.90%) 
Tumour lysis syndrome  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  2/5 (40.00%)  3/93 (3.23%) 
Musculoskeletal and connective tissue disorders             
Arthralgia  1  0/5 (0.00%)  0/7 (0.00%)  4/70 (5.71%)  0/6 (0.00%)  1/5 (20.00%)  5/93 (5.38%) 
Back pain  1  2/5 (40.00%)  2/7 (28.57%)  14/70 (20.00%)  0/6 (0.00%)  2/5 (40.00%)  20/93 (21.51%) 
Bone pain  1  1/5 (20.00%)  1/7 (14.29%)  7/70 (10.00%)  0/6 (0.00%)  1/5 (20.00%)  10/93 (10.75%) 
Muscular weakness  1  0/5 (0.00%)  0/7 (0.00%)  4/70 (5.71%)  0/6 (0.00%)  0/5 (0.00%)  4/93 (4.30%) 
Musculoskeletal pain  1  0/5 (0.00%)  0/7 (0.00%)  2/70 (2.86%)  0/6 (0.00%)  1/5 (20.00%)  3/93 (3.23%) 
Myalgia  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/93 (1.08%) 
Myopathy  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Neck pain  1  0/5 (0.00%)  1/7 (14.29%)  3/70 (4.29%)  0/6 (0.00%)  1/5 (20.00%)  5/93 (5.38%) 
Pain in extremity  1  3/5 (60.00%)  2/7 (28.57%)  8/70 (11.43%)  2/6 (33.33%)  2/5 (40.00%)  17/93 (18.28%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Skin papilloma  1  1/5 (20.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Nervous system disorders             
Aphasia  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Cognitive disorder  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  1/5 (20.00%)  2/93 (2.15%) 
Dizziness  1  1/5 (20.00%)  1/7 (14.29%)  3/70 (4.29%)  0/6 (0.00%)  0/5 (0.00%)  5/93 (5.38%) 
Dysaesthesia  1  1/5 (20.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Dyskinesia  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/93 (1.08%) 
Encephalopathy  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  1/6 (16.67%)  0/5 (0.00%)  2/93 (2.15%) 
Epilepsy  1  1/5 (20.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Essential tremor  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Headache  1  5/5 (100.00%)  4/7 (57.14%)  20/70 (28.57%)  0/6 (0.00%)  2/5 (40.00%)  31/93 (33.33%) 
Lethargy  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/93 (1.08%) 
Neuralgia  1  1/5 (20.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Peripheral sensory neuropathy  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/93 (1.08%) 
Tremor  1  0/5 (0.00%)  1/7 (14.29%)  4/70 (5.71%)  2/6 (33.33%)  0/5 (0.00%)  7/93 (7.53%) 
Psychiatric disorders             
Agitation  1  0/5 (0.00%)  1/7 (14.29%)  3/70 (4.29%)  0/6 (0.00%)  1/5 (20.00%)  5/93 (5.38%) 
Anxiety  1  1/5 (20.00%)  0/7 (0.00%)  4/70 (5.71%)  0/6 (0.00%)  1/5 (20.00%)  6/93 (6.45%) 
Confusional state  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  1/5 (20.00%)  2/93 (2.15%) 
Irritability  1  0/5 (0.00%)  0/7 (0.00%)  2/70 (2.86%)  0/6 (0.00%)  1/5 (20.00%)  3/93 (3.23%) 
Personality change  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/93 (1.08%) 
Renal and urinary disorders             
Dysuria  1  1/5 (20.00%)  1/7 (14.29%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  3/93 (3.23%) 
Haematuria  1  0/5 (0.00%)  0/7 (0.00%)  2/70 (2.86%)  1/6 (16.67%)  0/5 (0.00%)  3/93 (3.23%) 
Oliguria  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Proteinuria  1  0/5 (0.00%)  0/7 (0.00%)  2/70 (2.86%)  1/6 (16.67%)  0/5 (0.00%)  3/93 (3.23%) 
Renal failure chronic  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Renal tubular disorder  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Urinary retention  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  1/5 (20.00%)  2/93 (2.15%) 
Respiratory, thoracic and mediastinal disorders             
Atelectasis  1  0/5 (0.00%)  0/7 (0.00%)  3/70 (4.29%)  1/6 (16.67%)  0/5 (0.00%)  4/93 (4.30%) 
Cough  1  1/5 (20.00%)  0/7 (0.00%)  13/70 (18.57%)  0/6 (0.00%)  2/5 (40.00%)  16/93 (17.20%) 
Dyspnoea  1  0/5 (0.00%)  0/7 (0.00%)  2/70 (2.86%)  1/6 (16.67%)  0/5 (0.00%)  3/93 (3.23%) 
Epistaxis  1  0/5 (0.00%)  1/7 (14.29%)  10/70 (14.29%)  1/6 (16.67%)  0/5 (0.00%)  12/93 (12.90%) 
Hypoxia  1  0/5 (0.00%)  0/7 (0.00%)  2/70 (2.86%)  0/6 (0.00%)  1/5 (20.00%)  3/93 (3.23%) 
Laryngeal oedema  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/93 (1.08%) 
Lung disorder  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  1/6 (16.67%)  0/5 (0.00%)  2/93 (2.15%) 
Oropharyngeal pain  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  1/6 (16.67%)  0/5 (0.00%)  2/93 (2.15%) 
Pleural effusion  1  0/5 (0.00%)  0/7 (0.00%)  2/70 (2.86%)  0/6 (0.00%)  1/5 (20.00%)  3/93 (3.23%) 
Pneumonia aspiration  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Productive cough  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  0/6 (0.00%)  1/5 (20.00%)  2/93 (2.15%) 
Pulmonary oedema  1  0/5 (0.00%)  0/7 (0.00%)  1/70 (1.43%)  1/6 (16.67%)  1/5 (20.00%)  3/93 (3.23%) 
Wheezing  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/93 (1.08%) 
Skin and subcutaneous tissue disorders             
Alopecia  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Dermatitis diaper  1  0/5 (0.00%)  1/7 (14.29%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  2/93 (2.15%) 
Drug eruption  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Dry skin  1  0/5 (0.00%)  1/7 (14.29%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  2/93 (2.15%) 
Erythema  1  2/5 (40.00%)  0/7 (0.00%)  2/70 (2.86%)  0/6 (0.00%)  0/5 (0.00%)  4/93 (4.30%) 
Erythema nodosum  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Hair growth abnormal  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/93 (1.08%) 
Petechiae  1  1/5 (20.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Pruritus  1  1/5 (20.00%)  0/7 (0.00%)  2/70 (2.86%)  0/6 (0.00%)  0/5 (0.00%)  3/93 (3.23%) 
Rash  1  1/5 (20.00%)  1/7 (14.29%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  3/93 (3.23%) 
Rash maculo-papular  1  0/5 (0.00%)  2/7 (28.57%)  3/70 (4.29%)  1/6 (16.67%)  1/5 (20.00%)  7/93 (7.53%) 
Skin discolouration  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Trichorrhexis  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  1/6 (16.67%)  0/5 (0.00%)  1/93 (1.08%) 
Surgical and medical procedures             
Infusion  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Oxygen supplementation  1  0/5 (0.00%)  1/7 (14.29%)  1/70 (1.43%)  0/6 (0.00%)  0/5 (0.00%)  2/93 (2.15%) 
Parenteral nutrition  1  0/5 (0.00%)  1/7 (14.29%)  0/70 (0.00%)  0/6 (0.00%)  0/5 (0.00%)  1/93 (1.08%) 
Vascular disorders             
Capillary leak syndrome  1  0/5 (0.00%)  0/7 (0.00%)  2/70 (2.86%)  2/6 (33.33%)  0/5 (0.00%)  4/93 (4.30%) 
Flushing  1  0/5 (0.00%)  0/7 (0.00%)  3/70 (4.29%)  0/6 (0.00%)  1/5 (20.00%)  4/93 (4.30%) 
Haematoma  1  0/5 (0.00%)  0/7 (0.00%)  2/70 (2.86%)  0/6 (0.00%)  1/5 (20.00%)  3/93 (3.23%) 
Hyperaemia  1  0/5 (0.00%)  0/7 (0.00%)  0/70 (0.00%)  0/6 (0.00%)  1/5 (20.00%)  1/93 (1.08%) 
Hypertension  1  0/5 (0.00%)  5/7 (71.43%)  18/70 (25.71%)  2/6 (33.33%)  1/5 (20.00%)  26/93 (27.96%) 
Hypotension  1  0/5 (0.00%)  1/7 (14.29%)  10/70 (14.29%)  2/6 (33.33%)  1/5 (20.00%)  14/93 (15.05%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Amgen, Inc
Phone: 866-572-6436
Layout table for additonal information
Responsible Party: Amgen Research (Munich) GmbH
ClinicalTrials.gov Identifier: NCT01471782    
Other Study ID Numbers: MT103-205
2010-024264-18 ( EudraCT Number )
First Submitted: October 28, 2011
First Posted: November 16, 2011
Results First Submitted: September 23, 2016
Results First Posted: February 8, 2017
Last Update Posted: February 8, 2017