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Blinatumomab Versus Standard of Care Chemotherapy in Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)

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ClinicalTrials.gov Identifier: NCT02013167
Recruitment Status : Terminated
First Posted : December 17, 2013
Results First Posted : August 9, 2017
Last Update Posted : November 28, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia
Interventions Drug: Blinatumomab
Drug: Standard of Care Chemotherapy
Enrollment 405
Recruitment Details

This study was conducted at 101 centers in 21 countries in Asia, Australia, Europe, and Latin and North America.

The first participant was enrolled on 03 January 2014 and treated on 06 January 2014. The last participant enrolled on 25 September 2015 and the data cutoff date for this report was 04 January 2016.

Pre-assignment Details Participants were randomized in a 2:1 ratio to either blinatumomab or standard of care (SOC) chemotherapy regimens. Randomization was stratified by age (< 35 years vs ≥ 35 years), prior salvage therapy (yes vs no), and prior allogeneic hematopoietic stem cell transplantation (HSCT) (yes vs no) as assessed at the time of consent.
Arm/Group Title Standard of Care Chemotherapy Blinatumomab
Hide Arm/Group Description

Participants received one of four prespecified, investigator-chosen chemotherapy regimens for 2 induction cycles. Participants who achieved a bone marrow response, CR/CRh*/CRi within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of SOC chemotherapy.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive SOC therapy for an additional 12 months.

Participants received blinatumomab by continuous intravenous infusion (CIVI) over 4 weeks followed by a 2 week treatment-free interval for 2 induction cycles. Participants who achieved a bone marrow response, complete remission, or complete remission with partial or incomplete hematologic recovery (CR/CRh*/CRi) within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive blinatumomab for an additional 12 months (4 cycles), where 1 cycle consisted of 4 weeks of CIVI followed by an 8-week treatment-free period.

The initial dose of blinatumomab was 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 through day 29 and for all subsequent cycles.

Period Title: Overall Study
Started 134 271
Received Treatment 109 267
Completed 33 [1] 93 [2]
Not Completed 101 178
Reason Not Completed
Withdrawal by Subject             15             14
Sponsor Decision             1             3
Lost to Follow-up             0             1
Death             85             160
[1]
Indicates participants continuing study at time of data cut-off
[2]
Indicates participants continuing study at time of data cut-off; 22 were receiving treatment
Arm/Group Title Standard of Care Chemotherapy Blinatumomab Total
Hide Arm/Group Description

Participants received one of four prespecified, investigator-chosen chemotherapy regimens for 2 induction cycles. Participants who achieved a bone marrow response, CR/CRh*/CRi within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of SOC chemotherapy.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive SOC therapy for an additional 12 months.

Participants received blinatumomab by continuous intravenous infusion (CIVI) over 4 weeks followed by a 2 week treatment-free interval for 2 induction cycles. Participants who achieved a bone marrow response, complete remission, or complete remission with partial or incomplete hematologic recovery (CR/CRh*/CRi) within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive blinatumomab for an additional 12 months (4 cycles), where 1 cycle consisted of 4 weeks of CIVI followed by an 8-week treatment-free period.

The initial dose of blinatumomab was 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 through day 29 and for all subsequent cycles.

Total of all reporting groups
Overall Number of Baseline Participants 134 271 405
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 134 participants 271 participants 405 participants
41.1  (17.3) 40.8  (17.1) 40.9  (17.2)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 134 participants 271 participants 405 participants
< 35 years 60 124 184
35 to 54 years 33 80 113
55 to 64 years 26 34 60
≥ 65 years 15 33 48
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 134 participants 271 participants 405 participants
Female
57
  42.5%
109
  40.2%
166
  41.0%
Male
77
  57.5%
162
  59.8%
239
  59.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 134 participants 271 participants 405 participants
Hispanic or Latino
11
   8.2%
26
   9.6%
37
   9.1%
Not Hispanic or Latino
122
  91.0%
243
  89.7%
365
  90.1%
Unknown or Not Reported
1
   0.7%
2
   0.7%
3
   0.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 134 participants 271 participants 405 participants
American Indian or Alaska Native 1 4 5
Asian 9 19 28
Native Hawaiian or Other Pacific Islander 1 1 2
Black or African American 3 5 8
White 112 228 340
Multiple 0 2 2
Other 8 12 20
Age Stratification at Randomization  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 134 participants 271 participants 405 participants
< 35 years 60 123 183
≥ 35 years 74 148 222
Prior Salvage Therapy Stratification at Randomization  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 134 participants 271 participants 405 participants
Yes 80 164 244
No 54 107 161
Prior Allogeneic Hematopoietic Stem Cell Transplant (HCST)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 134 participants 271 participants 405 participants
Yes 46 94 140
No 88 177 265
Standard of Care Chemotherapy Regimen Received   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 134 participants 271 participants 405 participants
FLAG ± anthracycline 56 0 56
High-dose methotrexate 30 0 30
Clofarabine 26 0 26
HIDAC 22 0 22
[1]
Measure Description: FLAG = fludarabine, cytarabine arabinoside, and granulocyte colony-stimulating factor (filgrastim); HiDAC = high-dose cytarabine arabinoside
1.Primary Outcome
Title Overall Survival
Hide Description Overall survival (OS) was calculated from time of randomization until death due to any cause. Participants still alive were censored at the date they were last known to be alive.
Time Frame From randomization until the data cut-off date of 04 January 2016; median observation time was 11.8 months in the SOC group and 11.7 months in the blinatumomab group.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Standard of Care Chemotherapy Blinatumomab
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Participants received one of four prespecified, investigator-chosen chemotherapy regimens for 2 induction cycles. Participants who achieved a bone marrow response, CR/CRh*/CRi within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of SOC chemotherapy.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive SOC therapy for an additional 12 months.

Participants received blinatumomab by continuous intravenous infusion (CIVI) over 4 weeks followed by a 2 week treatment-free interval for 2 induction cycles. Participants who achieved a bone marrow response, complete remission, or complete remission with partial or incomplete hematologic recovery (CR/CRh*/CRi) within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive blinatumomab for an additional 12 months (4 cycles), where 1 cycle consisted of 4 weeks of CIVI followed by an 8-week treatment-free period.

The initial dose of blinatumomab was 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 through day 29 and for all subsequent cycles.

Overall Number of Participants Analyzed 134 271
Median (95% Confidence Interval)
Unit of Measure: months
4.0
(2.9 to 5.3)
7.7
(5.6 to 9.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Standard of Care Chemotherapy, Blinatumomab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments [Not Specified]
Method Stratified Log Rank
Comments Stratified by age (< 35 years; ≥ 35 years), prior salvage therapy (yes vs. no), and prior allogeneic HSCT (yes vs. no).
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.55 to 0.93
Estimation Comments Hazard ratio obtained from the Cox Proportional Hazard Model. A hazard ratio < 1.0 indicated a lower average event rate and longer survival time for blinatumomab relative to SOC chemotherapy.
2.Secondary Outcome
Title Percentage of Participants With Complete Remission Within 12 Weeks of Treatment Initiation
Hide Description

Participants were evaluated for efficacy at the end of each treatment cycle via a central bone marrow aspiration and local peripheral blood counts.

Complete Remission (CR) was defined as having ≤ 5% blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts: platelets > 100,000/μl, and absolute neutrophil count (ANC) > 1,000/μl. CR must have occurred within 12 weeks of the first dose of therapy.

Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Standard of Care Chemotherapy Blinatumomab
Hide Arm/Group Description:

Participants received one of four prespecified, investigator-chosen chemotherapy regimens for 2 induction cycles. Participants who achieved a bone marrow response, CR/CRh*/CRi within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of SOC chemotherapy.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive SOC therapy for an additional 12 months.

Participants received blinatumomab by continuous intravenous infusion (CIVI) over 4 weeks followed by a 2 week treatment-free interval for 2 induction cycles. Participants who achieved a bone marrow response, complete remission, or complete remission with partial or incomplete hematologic recovery (CR/CRh*/CRi) within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive blinatumomab for an additional 12 months (4 cycles), where 1 cycle consisted of 4 weeks of CIVI followed by an 8-week treatment-free period.

The initial dose of blinatumomab was 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 through day 29 and for all subsequent cycles.

Overall Number of Participants Analyzed 134 271
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
15.7
(10.0 to 23.0)
33.6
(28.0 to 39.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Standard of Care Chemotherapy, Blinatumomab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Adjusted for the stratification factors: age (< 35 vs. ≥ 35), prior salvage therapy (yes vs. no), and prior allogeneic HSCT (yes vs. no).
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 17.9
Confidence Interval (2-Sided) 95%
9.6 to 26.2
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Complete Remission/Complete Remission With Partial Hematological Recovery/Complete Remission With Incomplete Hematological Recovery (CR/CRh*/CRi) Within 12 Weeks of Treatment Initiation
Hide Description

Participants were evaluated for efficacy at the end of each treatment cycle via a central bone marrow aspiration and local peripheral blood counts.

Complete remission was defined as having ≤ 5% blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts: platelets > 100,000/μl, and ANC > 1,000/μl.

Complete Remission with partial hematological recovery (CRh*) was defined as ≤ 5% blasts in the bone marrow, no evidence of disease and partial recovery of peripheral blood counts: platelets > 50,000/μl, and ANC > 500/μl.

Complete remission with incomplete hematological recovery (CRi) was defined as ≤ 5% blasts in the bone marrow, no evidence of disease and incomplete recovery of peripheral blood counts: platelets > 100,000/μl or ANC > 1000 (but not both).

Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Standard of Care Chemotherapy Blinatumomab
Hide Arm/Group Description:

Participants received one of four prespecified, investigator-chosen chemotherapy regimens for 2 induction cycles. Participants who achieved a bone marrow response, CR/CRh*/CRi within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of SOC chemotherapy.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive SOC therapy for an additional 12 months.

Participants received blinatumomab by continuous intravenous infusion (CIVI) over 4 weeks followed by a 2 week treatment-free interval for 2 induction cycles. Participants who achieved a bone marrow response, complete remission, or complete remission with partial or incomplete hematologic recovery (CR/CRh*/CRi) within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive blinatumomab for an additional 12 months (4 cycles), where 1 cycle consisted of 4 weeks of CIVI followed by an 8-week treatment-free period.

The initial dose of blinatumomab was 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 through day 29 and for all subsequent cycles.

Overall Number of Participants Analyzed 134 271
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
24.6
(17.6 to 32.8)
43.9
(37.9 to 50.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Standard of Care Chemotherapy, Blinatumomab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Adjusted for the stratification factors: age (< 35 vs. ≥ 35), prior salvage therapy (yes vs. no), and prior allogeneic HSCT (yes vs. no).
Method of Estimation Estimation Parameter Treatment difference
Estimated Value 19.3
Confidence Interval (2-Sided) 95%
9.9 to 28.7
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Event Free Survival (EFS)
Hide Description

Event free survival was defined as the time from randomization until a documented relapse after achieving CR/CRh*/CRi or death, whichever occurred first. Participants who failed to achieve a CR/CRh*/CRi within 12 weeks of treatment initiation were considered as non-responders and assigned an EFS duration of 1 day. Participants still alive and relapse-free were censored on their last disease assessment date.

A relapse event was any one of the following:

  • Hematological relapse: proportion of blasts in bone marrow >5% or blasts in peripheral blood after documented CR or CRh* or CRi
  • Progressive disease: An increase from baseline of at least 25% of bone marrow blasts or an absolute increase of at least 5,000 cells/μL in the number of circulating leukemia cells
  • Extramedullary relapse: extramedullary lesion that is new or increased by 50% from nadir as assessed by Cheson criteria.

The Kaplan-Meier estimate of EFS at 6 months is reported.

Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Standard of Care Chemotherapy Blinatumomab
Hide Arm/Group Description:

Participants received one of four prespecified, investigator-chosen chemotherapy regimens for 2 induction cycles. Participants who achieved a bone marrow response, CR/CRh*/CRi within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of SOC chemotherapy.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive SOC therapy for an additional 12 months.

Participants received blinatumomab by continuous intravenous infusion (CIVI) over 4 weeks followed by a 2 week treatment-free interval for 2 induction cycles. Participants who achieved a bone marrow response, complete remission, or complete remission with partial or incomplete hematologic recovery (CR/CRh*/CRi) within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive blinatumomab for an additional 12 months (4 cycles), where 1 cycle consisted of 4 weeks of CIVI followed by an 8-week treatment-free period.

The initial dose of blinatumomab was 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 through day 29 and for all subsequent cycles.

Overall Number of Participants Analyzed 134 271
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
12.5
(7.2 to 19.2)
30.7
(25.0 to 36.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Standard of Care Chemotherapy, Blinatumomab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.55
Confidence Interval (2-Sided) 95%
0.43 to 0.71
Estimation Comments The hazard ratio estimates were obtained from the Cox Proportional Hazard Model. A hazard ratio < 1.0 indicates a lower average event rate and a longer survival for Blinatumomab relative to SOC Chemotherapy.
5.Secondary Outcome
Title Duration of Complete Remission
Hide Description Duration of complete remission, calculated only for participants who achieved a CR, was calculated from the date a CR was first achieved until the earliest date of a disease assessment indicating a relapse event or death, whichever occurred first. Participants who did not have a relapse event were censored on their last disease assessment date.
Time Frame Up to the data cut-off date of 04 January 2016; median observation time was 10.8 months in the SOC group and 7.0 months in the blinatumomab group.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with a best response of complete remission within 12 weeks of treatment initiation.
Arm/Group Title Standard of Care Chemotherapy Blinatumomab
Hide Arm/Group Description:

Participants received one of four prespecified, investigator-chosen chemotherapy regimens for 2 induction cycles. Participants who achieved a bone marrow response, CR/CRh*/CRi within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of SOC chemotherapy.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive SOC therapy for an additional 12 months.

Participants received blinatumomab by continuous intravenous infusion (CIVI) over 4 weeks followed by a 2 week treatment-free interval for 2 induction cycles. Participants who achieved a bone marrow response, complete remission, or complete remission with partial or incomplete hematologic recovery (CR/CRh*/CRi) within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive blinatumomab for an additional 12 months (4 cycles), where 1 cycle consisted of 4 weeks of CIVI followed by an 8-week treatment-free period.

The initial dose of blinatumomab was 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 through day 29 and for all subsequent cycles.

Overall Number of Participants Analyzed 21 91
Median (95% Confidence Interval)
Unit of Measure: months
7.8
(2.2 to 19.0)
8.3
(5.7 to 10.7)
6.Secondary Outcome
Title Duration of Complete Remission/Complete Remission With Partial Hematological Recovery/Complete Remission With Incomplete Hematological Recovery (CR/CRh*/CRi)
Hide Description Duration of CR/CRh*/CRi, calculated only for participants who achieved a CR/CRh*/CRi, was calculated from the date a CR/CRh*/CRi was first achieved until the earliest date of a disease assessment indicating a relapse event or death, whichever occurred first. Participants who did not have a relapse event were censored on their last disease assessment date.
Time Frame Up to the data cut-off date of 04 January 2016; median observation time was 10.8 months in the SOC group and 7.2 months in the blinatumomab group.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized participants with a best response of CR/CRh*/CRi within 12 weeks of treatment initiation.
Arm/Group Title Standard of Care Chemotherapy Blinatumomab
Hide Arm/Group Description:

Participants received one of four prespecified, investigator-chosen chemotherapy regimens for 2 induction cycles. Participants who achieved a bone marrow response, CR/CRh*/CRi within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of SOC chemotherapy.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive SOC therapy for an additional 12 months.

Participants received blinatumomab by continuous intravenous infusion (CIVI) over 4 weeks followed by a 2 week treatment-free interval for 2 induction cycles. Participants who achieved a bone marrow response, complete remission, or complete remission with partial or incomplete hematologic recovery (CR/CRh*/CRi) within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive blinatumomab for an additional 12 months (4 cycles), where 1 cycle consisted of 4 weeks of CIVI followed by an 8-week treatment-free period.

The initial dose of blinatumomab was 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 through day 29 and for all subsequent cycles.

Overall Number of Participants Analyzed 33 119
Median (95% Confidence Interval)
Unit of Measure: months
4.6
(1.8 to 19.0)
7.3
(5.8 to 9.9)
7.Secondary Outcome
Title Percentage of Participants With Minimal Residual Disease (MRD) Within 12 Weeks of Treatment Initiation
Hide Description Bone marrow samples were evaluated for MRD remission by a central laboratory. MRD remission was defined as the occurrence of an MRD level below 10^-4 measured by quantitative reverse transcription polymerase chain reaction (PCR) or flow cytometry.
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Standard of Care Chemotherapy Blinatumomab
Hide Arm/Group Description:

Participants received one of four prespecified, investigator-chosen chemotherapy regimens for 2 induction cycles. Participants who achieved a bone marrow response, CR/CRh*/CRi within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of SOC chemotherapy.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive SOC therapy for an additional 12 months.

Participants received blinatumomab by continuous intravenous infusion (CIVI) over 4 weeks followed by a 2 week treatment-free interval for 2 induction cycles. Participants who achieved a bone marrow response, complete remission, or complete remission with partial or incomplete hematologic recovery (CR/CRh*/CRi) within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive blinatumomab for an additional 12 months (4 cycles), where 1 cycle consisted of 4 weeks of CIVI followed by an 8-week treatment-free period.

The initial dose of blinatumomab was 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 through day 29 and for all subsequent cycles.

Overall Number of Participants Analyzed 134 271
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
14.2
(8.8 to 21.3)
29.9
(24.5 to 35.7)
8.Secondary Outcome
Title Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT)
Hide Description [Not Specified]
Time Frame Up to the data cut-off date of 04 January 2016; maximum time on study was 23 months.
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants
Arm/Group Title Standard of Care Chemotherapy Blinatumomab
Hide Arm/Group Description:

Participants received one of four prespecified, investigator-chosen chemotherapy regimens for 2 induction cycles. Participants who achieved a bone marrow response, CR/CRh*/CRi within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of SOC chemotherapy.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive SOC therapy for an additional 12 months.

Participants received blinatumomab by continuous intravenous infusion (CIVI) over 4 weeks followed by a 2 week treatment-free interval for 2 induction cycles. Participants who achieved a bone marrow response, complete remission, or complete remission with partial or incomplete hematologic recovery (CR/CRh*/CRi) within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive blinatumomab for an additional 12 months (4 cycles), where 1 cycle consisted of 4 weeks of CIVI followed by an 8-week treatment-free period.

The initial dose of blinatumomab was 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 through day 29 and for all subsequent cycles.

Overall Number of Participants Analyzed 134 271
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
23.9
(16.9 to 32.0)
24.0
(19.0 to 29.5)
9.Secondary Outcome
Title Number of Participants With Adverse Events
Hide Description

Adverse events (AEs) were graded for severity according to the CTCAE version 4.0, where Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.

Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living.

Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living.

Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. Treatment-related adverse events (TRAEs) were those assessed by the investigator as possibly related to blinatumomab based on response to the question: Is there a reasonable possibility that the event may have been caused by blinatumomab or other protocol-specified therapies/procedures?

Time Frame From first dose of protocol-specified therapy until 30 days after the last dose, up to the data cut-off date of 04 January 2016; median duration of treatment was 5 days in the SOC group and 70 days in the blinatumomab group.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received protocol-specified therapy analyzed according to the treatment they received.
Arm/Group Title Standard of Care Chemotherapy Blinatumomab
Hide Arm/Group Description:

Participants received one of four prespecified, investigator-chosen chemotherapy regimens for 2 induction cycles. Participants who achieved a bone marrow response, CR/CRh*/CRi within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of SOC chemotherapy.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive SOC therapy for an additional 12 months.

Participants received blinatumomab by continuous intravenous infusion (CIVI) over 4 weeks followed by a 2 week treatment-free interval for 2 induction cycles. Participants who achieved a bone marrow response, complete remission, or complete remission with partial or incomplete hematologic recovery (CR/CRh*/CRi) within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive blinatumomab for an additional 12 months (4 cycles), where 1 cycle consisted of 4 weeks of CIVI followed by an 8-week treatment-free period.

The initial dose of blinatumomab was 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 through day 29 and for all subsequent cycles.

Overall Number of Participants Analyzed 109 267
Measure Type: Number
Unit of Measure: participants
Any adverse event 108 263
AE grade ≥ 2 106 256
AE grade ≥ 3 100 231
AE grade ≥ 4 67 133
Serious adverse events 49 165
AEs leading to interruption of study drug 6 86
AEs leading to discontinuation of study drug 9 33
Life-threatening adverse events 26 55
Fatal adverse events 19 51
Treatment-related adverse events 92 214
Treatment-related AE grade ≥ 2 89 195
Treatment-related AE grade ≥ 3 78 143
Treatment-related AE grade ≥ 4 51 57
Serious treatment-related adverse events 34 74
TRAEs leading to interruption of study drug 6 58
TRAEs leading to discontinuation of study drug 8 19
Treatment-related life-threatening adverse events 17 21
Treatment-related fatal adverse events 8 8
10.Secondary Outcome
Title 100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplant
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The analysis of 100-day mortality after allogeneic HSCT was assessed for participants who achieved a best response of CR/CRh*CTi within 12 weeks of treatment initiation, who received an allogeneic HSCT and did not receive any additional anticancer treatment before the transplant. 100-day mortality after allogeneic HSCT was calculated relative to the date of allogeneic HSCT.

The 100-day mortality rate after allogeneic HSCT was defined as the percentage of participants having died up to 100 days after allogeneic HSCT estimated using the estimated time to death in percent calculated by Kaplan-Meier methods. Participants alive were censored on the last documented visit date or the date of the last phone contact when the patient was last known to have been alive.

Time Frame 100 days, from the date of allogeneic HSCT until the data cut-off date of 04 January 2016
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Randomized participants with a best response of CR/CRh*/CRi within 12 weeks of treatment initiation and who received an allogeneic HSC without anti-cancer therapy prior to allogeneic HSCT.
Arm/Group Title Standard of Care Chemotherapy Blinatumomab
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Participants received one of four prespecified, investigator-chosen chemotherapy regimens for 2 induction cycles. Participants who achieved a bone marrow response, CR/CRh*/CRi within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of SOC chemotherapy.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive SOC therapy for an additional 12 months.

Participants received blinatumomab by continuous intravenous infusion (CIVI) over 4 weeks followed by a 2 week treatment-free interval for 2 induction cycles. Participants who achieved a bone marrow response, complete remission, or complete remission with partial or incomplete hematologic recovery (CR/CRh*/CRi) within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive blinatumomab for an additional 12 months (4 cycles), where 1 cycle consisted of 4 weeks of CIVI followed by an 8-week treatment-free period.

The initial dose of blinatumomab was 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 through day 29 and for all subsequent cycles.

Overall Number of Participants Analyzed 12 38
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.0 [1] 
(NA to NA)
12.4
(4.8 to 29.9)
[1]
Could not be estimated due to the low number of events
11.Secondary Outcome
Title Number of Participants With Anti-blinatumomab Antibodies
Hide Description Anti-blinatumomab binding antibodies were evaluated using a validated electrochemiluminescence (ECL)-based assay (binding assay). Samples positive for binding were analyzed using a cell-based bioassay to determine if the detected antibodies had neutralizing properties (neutralizing assay).
Time Frame Samples were collected on day 29 at the end of cycle 2 and 30 days after the last dose of blinatumomab (median duration of treatment was 70 days).
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Participants who received blinatumomab with available post-baseline antibody data.
Arm/Group Title Blinatumomab
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Participants received blinatumomab by continuous intravenous infusion (CIVI) over 4 weeks followed by a 2 week treatment-free interval for 2 induction cycles. Participants who achieved a bone marrow response, complete remission, or complete remission with partial or incomplete hematologic recovery (CR/CRh*/CRi) within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive blinatumomab for an additional 12 months (4 cycles), where 1 cycle consisted of 4 weeks of CIVI followed by an 8-week treatment-free period.

The initial dose of blinatumomab was 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 through day 29 and for all subsequent cycles.

Overall Number of Participants Analyzed 171
Measure Type: Number
Unit of Measure: participants
Binding antibody positive 5
Neutralizing antibody positive 3
12.Secondary Outcome
Title Time to a 10-point Decrease From Baseline in Global Health Status and Quality of Life or Death
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The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) is a 30-item questionnaire that assesses the health related quality of life of cancer patients. The EORTC QLQ-C30 consists of a global health status/quality of life (QoL) scale, 5 functional scales, 3 symptom scales, and 6 single items.

The global health/QoL scale consists of 2 questions that ask participants to rate their overall health and overall quality of life durig the past week on a scale from 1 (very poor) to 7 (excellent). The scale score was derived as the sum of each score and transformed to a scale from 0 to 100 where higher scores represent a high QoL.

Time to a ≥10-point decrease from baseline GHS/QoL or death, whichever came first, was calculated from baseline. Participants still alive and without a 10-point decrease in GHS/QoL EORTC QLQ-C30 were censored on their last EORTC QLQ-C30 assessment date.

Time Frame From randomization until the data cut-off date of 04 January 2016; EORTC QLQ-C30 was assessed on day 1, 8, 15, and 29 during cycle 1; days 1, 15, and 29 in cycle 2 and each consolidation cycle, and 30-days following the last dose of drug treatment.
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EORTC QLQ-C30 analysis set included all randomized participants with a non-missing baseline and at least 1 non-missing postbaseline result of any EORTC QLQ-C30 scales/item.
Arm/Group Title Standard of Care Chemotherapy Blinatumomab
Hide Arm/Group Description:

Participants received one of four prespecified, investigator-chosen chemotherapy regimens for 2 induction cycles. Participants who achieved a bone marrow response, CR/CRh*/CRi within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of SOC chemotherapy.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive SOC therapy for an additional 12 months.

Participants received blinatumomab by continuous intravenous infusion (CIVI) over 4 weeks followed by a 2 week treatment-free interval for 2 induction cycles. Participants who achieved a bone marrow response, complete remission, or complete remission with partial or incomplete hematologic recovery (CR/CRh*/CRi) within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive blinatumomab for an additional 12 months (4 cycles), where 1 cycle consisted of 4 weeks of CIVI followed by an 8-week treatment-free period.

The initial dose of blinatumomab was 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 through day 29 and for all subsequent cycles.

Overall Number of Participants Analyzed 95 247
Median (95% Confidence Interval)
Unit of Measure: months
1.0
(0.5 to 1.5)
1.7
(1.1 to 3.6)
Time Frame From first dose of protocol-specified therapy until 30 days after the last dose, up to the data cut-off date of 04 January 2016; median duration of treatment was 5 days in the SOC group and 70 days in the blinatumomab group.
Adverse Event Reporting Description Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
 
Arm/Group Title Standard of Care Chemotherapy Blinatumomab
Hide Arm/Group Description

Participants received one of four prespecified, investigator-chosen chemotherapy regimens for 2 induction cycles. Participants who achieved a bone marrow response, CR/CRh*/CRi within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of SOC chemotherapy.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive SOC therapy for an additional 12 months.

Participants received blinatumomab by continuous intravenous infusion (CIVI) over 4 weeks followed by a 2 week treatment-free interval for 2 induction cycles. Participants who achieved a bone marrow response, complete remission, or complete remission with partial or incomplete hematologic recovery (CR/CRh*/CRi) within 2 induction cycles of treatment could receive up to 3 additional consolidation cycles of blinatumomab.

Participants who received 2 induction and up to 3 consolidation cycles of therapy and continued to have a bone marrow response or CR/CRh*/CRi could continue to receive blinatumomab for an additional 12 months (4 cycles), where 1 cycle consisted of 4 weeks of CIVI followed by an 8-week treatment-free period.

The initial dose of blinatumomab was 9 μg/day for the first 7 days of treatment, increased to 28 μg/day starting on day 8 through day 29 and for all subsequent cycles.

All-Cause Mortality
Standard of Care Chemotherapy Blinatumomab
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Standard of Care Chemotherapy Blinatumomab
Affected / at Risk (%) Affected / at Risk (%)
Total   49/109 (44.95%)   165/267 (61.80%) 
Blood and lymphatic system disorders     
Agranulocytosis  1  1/109 (0.92%)  0/267 (0.00%) 
Anaemia  1  0/109 (0.00%)  1/267 (0.37%) 
Febrile bone marrow aplasia  1  0/109 (0.00%)  1/267 (0.37%) 
Febrile neutropenia  1  12/109 (11.01%)  23/267 (8.61%) 
Histiocytosis haematophagic  1  0/109 (0.00%)  3/267 (1.12%) 
Leukocytosis  1  0/109 (0.00%)  3/267 (1.12%) 
Leukopenia  1  1/109 (0.92%)  0/267 (0.00%) 
Lymphadenopathy  1  0/109 (0.00%)  1/267 (0.37%) 
Neutropenia  1  2/109 (1.83%)  2/267 (0.75%) 
Pancytopenia  1  1/109 (0.92%)  3/267 (1.12%) 
Thrombocytopenia  1  1/109 (0.92%)  0/267 (0.00%) 
Cardiac disorders     
Acute myocardial infarction  1  0/109 (0.00%)  1/267 (0.37%) 
Atrial fibrillation  1  0/109 (0.00%)  1/267 (0.37%) 
Atrial flutter  1  0/109 (0.00%)  1/267 (0.37%) 
Cardiac arrest  1  1/109 (0.92%)  1/267 (0.37%) 
Cardiac failure congestive  1  0/109 (0.00%)  1/267 (0.37%) 
Cardiac tamponade  1  1/109 (0.92%)  0/267 (0.00%) 
Cardiopulmonary failure  1  0/109 (0.00%)  1/267 (0.37%) 
Pericardial effusion  1  0/109 (0.00%)  1/267 (0.37%) 
Supraventricular tachycardia  1  1/109 (0.92%)  0/267 (0.00%) 
Congenital, familial and genetic disorders     
Aplasia  1  0/109 (0.00%)  1/267 (0.37%) 
Gastrointestinal disorders     
Abdominal pain  1  0/109 (0.00%)  2/267 (0.75%) 
Gastric haemorrhage  1  0/109 (0.00%)  1/267 (0.37%) 
Gastrointestinal inflammation  1  1/109 (0.92%)  0/267 (0.00%) 
Gastrointestinal necrosis  1  0/109 (0.00%)  1/267 (0.37%) 
Haematemesis  1  0/109 (0.00%)  1/267 (0.37%) 
Mouth haemorrhage  1  1/109 (0.92%)  0/267 (0.00%) 
Nausea  1  0/109 (0.00%)  1/267 (0.37%) 
Pancreatitis  1  1/109 (0.92%)  0/267 (0.00%) 
Stomatitis  1  0/109 (0.00%)  1/267 (0.37%) 
Vomiting  1  0/109 (0.00%)  2/267 (0.75%) 
General disorders     
Asthenia  1  0/109 (0.00%)  2/267 (0.75%) 
Chest pain  1  0/109 (0.00%)  1/267 (0.37%) 
Death  1  0/109 (0.00%)  1/267 (0.37%) 
Discomfort  1  0/109 (0.00%)  1/267 (0.37%) 
General physical health deterioration  1  0/109 (0.00%)  2/267 (0.75%) 
Hyperthermia  1  0/109 (0.00%)  1/267 (0.37%) 
Medical device complication  1  0/109 (0.00%)  1/267 (0.37%) 
Multi-organ failure  1  1/109 (0.92%)  4/267 (1.50%) 
Oedema peripheral  1  0/109 (0.00%)  1/267 (0.37%) 
Pyrexia  1  1/109 (0.92%)  16/267 (5.99%) 
Systemic inflammatory response syndrome  1  0/109 (0.00%)  1/267 (0.37%) 
Hepatobiliary disorders     
Acute hepatic failure  1  1/109 (0.92%)  0/267 (0.00%) 
Cholelithiasis  1  0/109 (0.00%)  1/267 (0.37%) 
Cholestasis  1  1/109 (0.92%)  0/267 (0.00%) 
Hepatitis  1  0/109 (0.00%)  1/267 (0.37%) 
Immune system disorders     
Acute graft versus host disease in skin  1  0/109 (0.00%)  1/267 (0.37%) 
Anaphylactic shock  1  0/109 (0.00%)  1/267 (0.37%) 
Cytokine release syndrome  1  0/109 (0.00%)  7/267 (2.62%) 
Graft versus host disease  1  0/109 (0.00%)  1/267 (0.37%) 
Graft versus host disease in liver  1  0/109 (0.00%)  1/267 (0.37%) 
Infections and infestations     
Abscess fungal  1  1/109 (0.92%)  0/267 (0.00%) 
Bacteraemia  1  3/109 (2.75%)  2/267 (0.75%) 
Bacterial infection  1  0/109 (0.00%)  2/267 (0.75%) 
Bacterial sepsis  1  2/109 (1.83%)  6/267 (2.25%) 
Brain abscess  1  1/109 (0.92%)  0/267 (0.00%) 
Bronchitis  1  0/109 (0.00%)  1/267 (0.37%) 
Bronchopulmonary aspergillosis  1  1/109 (0.92%)  4/267 (1.50%) 
Catheter site infection  1  0/109 (0.00%)  2/267 (0.75%) 
Cellulitis  1  0/109 (0.00%)  1/267 (0.37%) 
Central nervous system abscess  1  1/109 (0.92%)  0/267 (0.00%) 
Citrobacter infection  1  0/109 (0.00%)  1/267 (0.37%) 
Citrobacter sepsis  1  1/109 (0.92%)  0/267 (0.00%) 
Device related infection  1  1/109 (0.92%)  6/267 (2.25%) 
Device related sepsis  1  2/109 (1.83%)  1/267 (0.37%) 
Encephalitis enteroviral  1  0/109 (0.00%)  1/267 (0.37%) 
Enterococcal bacteraemia  1  1/109 (0.92%)  0/267 (0.00%) 
Enterococcal infection  1  1/109 (0.92%)  0/267 (0.00%) 
Escherichia infection  1  0/109 (0.00%)  2/267 (0.75%) 
Fungaemia  1  0/109 (0.00%)  1/267 (0.37%) 
Fungal infection  1  1/109 (0.92%)  0/267 (0.00%) 
Fungal sepsis  1  0/109 (0.00%)  2/267 (0.75%) 
Fusarium infection  1  1/109 (0.92%)  0/267 (0.00%) 
Gastroenteritis  1  0/109 (0.00%)  2/267 (0.75%) 
Hepatosplenic candidiasis  1  1/109 (0.92%)  0/267 (0.00%) 
Infection  1  0/109 (0.00%)  1/267 (0.37%) 
Infection in an immunocompromised host  1  0/109 (0.00%)  1/267 (0.37%) 
Influenza  1  0/109 (0.00%)  1/267 (0.37%) 
Lower respiratory tract infection  1  0/109 (0.00%)  1/267 (0.37%) 
Lower respiratory tract infection fungal  1  0/109 (0.00%)  1/267 (0.37%) 
Lung infection  1  1/109 (0.92%)  1/267 (0.37%) 
Mastoiditis  1  0/109 (0.00%)  1/267 (0.37%) 
Meningitis bacterial  1  0/109 (0.00%)  1/267 (0.37%) 
Mucormycosis  1  0/109 (0.00%)  1/267 (0.37%) 
Muscle abscess  1  0/109 (0.00%)  1/267 (0.37%) 
Neutropenic sepsis  1  1/109 (0.92%)  3/267 (1.12%) 
Osteomyelitis  1  0/109 (0.00%)  1/267 (0.37%) 
Otitis media acute  1  0/109 (0.00%)  1/267 (0.37%) 
Pneumonia  1  2/109 (1.83%)  10/267 (3.75%) 
Pneumonia bacterial  1  0/109 (0.00%)  1/267 (0.37%) 
Pneumonia fungal  1  2/109 (1.83%)  1/267 (0.37%) 
Pneumonia pseudomonal  1  0/109 (0.00%)  1/267 (0.37%) 
Pneumonia respiratory syncytial viral  1  0/109 (0.00%)  1/267 (0.37%) 
Progressive multifocal leukoencephalopathy  1  0/109 (0.00%)  1/267 (0.37%) 
Pseudomonal sepsis  1  1/109 (0.92%)  3/267 (1.12%) 
Pseudomonas infection  1  1/109 (0.92%)  3/267 (1.12%) 
Pulmonary mycosis  1  0/109 (0.00%)  1/267 (0.37%) 
Respiratory syncytial virus bronchiolitis  1  0/109 (0.00%)  1/267 (0.37%) 
Rhinovirus infection  1  1/109 (0.92%)  0/267 (0.00%) 
Sepsis  1  7/109 (6.42%)  13/267 (4.87%) 
Sepsis syndrome  1  0/109 (0.00%)  1/267 (0.37%) 
Septic shock  1  3/109 (2.75%)  8/267 (3.00%) 
Sinusitis  1  0/109 (0.00%)  1/267 (0.37%) 
Skin infection  1  0/109 (0.00%)  1/267 (0.37%) 
Soft tissue infection  1  1/109 (0.92%)  0/267 (0.00%) 
Staphylococcal infection  1  1/109 (0.92%)  2/267 (0.75%) 
Staphylococcal sepsis  1  0/109 (0.00%)  1/267 (0.37%) 
Streptococcal sepsis  1  1/109 (0.92%)  0/267 (0.00%) 
Systemic candida  1  1/109 (0.92%)  0/267 (0.00%) 
Tooth infection  1  0/109 (0.00%)  1/267 (0.37%) 
Injury, poisoning and procedural complications     
Accidental overdose  1  0/109 (0.00%)  3/267 (1.12%) 
Ankle fracture  1  1/109 (0.92%)  0/267 (0.00%) 
Fall  1  0/109 (0.00%)  1/267 (0.37%) 
Medication error  1  0/109 (0.00%)  1/267 (0.37%) 
Overdose  1  0/109 (0.00%)  8/267 (3.00%) 
Subdural haematoma  1  0/109 (0.00%)  1/267 (0.37%) 
Subdural haemorrhage  1  0/109 (0.00%)  1/267 (0.37%) 
Investigations     
Blood bilirubin increased  1  0/109 (0.00%)  2/267 (0.75%) 
Blood lactate dehydrogenase increased  1  0/109 (0.00%)  1/267 (0.37%) 
CSF cell count abnormal  1  0/109 (0.00%)  1/267 (0.37%) 
Platelet count decreased  1  0/109 (0.00%)  1/267 (0.37%) 
Transaminases increased  1  0/109 (0.00%)  1/267 (0.37%) 
Weight increased  1  0/109 (0.00%)  1/267 (0.37%) 
White blood cell count decreased  1  0/109 (0.00%)  1/267 (0.37%) 
White blood cell count increased  1  0/109 (0.00%)  1/267 (0.37%) 
Metabolism and nutrition disorders     
Hypercalcaemia  1  0/109 (0.00%)  1/267 (0.37%) 
Hyperkalaemia  1  1/109 (0.92%)  0/267 (0.00%) 
Hyperuricaemia  1  0/109 (0.00%)  2/267 (0.75%) 
Hypoglycaemia  1  1/109 (0.92%)  0/267 (0.00%) 
Hypokalaemia  1  0/109 (0.00%)  1/267 (0.37%) 
Hypomagnesaemia  1  0/109 (0.00%)  1/267 (0.37%) 
Hypophosphataemia  1  0/109 (0.00%)  2/267 (0.75%) 
Lactic acidosis  1  1/109 (0.92%)  1/267 (0.37%) 
Metabolic acidosis  1  1/109 (0.92%)  0/267 (0.00%) 
Tumour lysis syndrome  1  0/109 (0.00%)  3/267 (1.12%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  0/109 (0.00%)  2/267 (0.75%) 
Bone pain  1  0/109 (0.00%)  3/267 (1.12%) 
Osteitis  1  1/109 (0.92%)  0/267 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute lymphocytic leukaemia  1  0/109 (0.00%)  1/267 (0.37%) 
Leukaemic infiltration extramedullary  1  0/109 (0.00%)  1/267 (0.37%) 
Leukaemic infiltration pulmonary  1  0/109 (0.00%)  1/267 (0.37%) 
Tumour associated fever  1  0/109 (0.00%)  1/267 (0.37%) 
Nervous system disorders     
Aphasia  1  0/109 (0.00%)  3/267 (1.12%) 
Cerebral haemorrhage  1  0/109 (0.00%)  1/267 (0.37%) 
Cognitive disorder  1  0/109 (0.00%)  1/267 (0.37%) 
Depressed level of consciousness  1  0/109 (0.00%)  1/267 (0.37%) 
Encephalopathy  1  0/109 (0.00%)  4/267 (1.50%) 
Generalised tonic-clonic seizure  1  1/109 (0.92%)  0/267 (0.00%) 
Haemorrhage intracranial  1  2/109 (1.83%)  1/267 (0.37%) 
Haemorrhagic stroke  1  0/109 (0.00%)  1/267 (0.37%) 
Hemianopia  1  0/109 (0.00%)  1/267 (0.37%) 
Hemiparesis  1  0/109 (0.00%)  1/267 (0.37%) 
Hemiplegia  1  1/109 (0.92%)  0/267 (0.00%) 
Hypoaesthesia  1  0/109 (0.00%)  1/267 (0.37%) 
Intention tremor  1  0/109 (0.00%)  1/267 (0.37%) 
Leukoencephalopathy  1  0/109 (0.00%)  1/267 (0.37%) 
Neurological symptom  1  0/109 (0.00%)  1/267 (0.37%) 
Paraesthesia  1  0/109 (0.00%)  1/267 (0.37%) 
Seizure  1  1/109 (0.92%)  1/267 (0.37%) 
Somnolence  1  0/109 (0.00%)  1/267 (0.37%) 
Status epilepticus  1  0/109 (0.00%)  1/267 (0.37%) 
Tremor  1  0/109 (0.00%)  1/267 (0.37%) 
Psychiatric disorders     
Completed suicide  1  0/109 (0.00%)  1/267 (0.37%) 
Mental status changes  1  0/109 (0.00%)  1/267 (0.37%) 
Renal and urinary disorders     
Acute kidney injury  1  2/109 (1.83%)  3/267 (1.12%) 
Calculus ureteric  1  0/109 (0.00%)  1/267 (0.37%) 
Urinary bladder haemorrhage  1  1/109 (0.92%)  0/267 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  0/109 (0.00%)  2/267 (0.75%) 
Dyspnoea  1  0/109 (0.00%)  2/267 (0.75%) 
Epistaxis  1  0/109 (0.00%)  2/267 (0.75%) 
Haemoptysis  1  0/109 (0.00%)  2/267 (0.75%) 
Hypoxia  1  0/109 (0.00%)  1/267 (0.37%) 
Lung infiltration  1  1/109 (0.92%)  1/267 (0.37%) 
Pleural effusion  1  1/109 (0.92%)  1/267 (0.37%) 
Pneumonitis  1  0/109 (0.00%)  1/267 (0.37%) 
Pneumothorax  1  1/109 (0.92%)  0/267 (0.00%) 
Pulmonary oedema  1  0/109 (0.00%)  1/267 (0.37%) 
Respiratory arrest  1  0/109 (0.00%)  1/267 (0.37%) 
Respiratory failure  1  2/109 (1.83%)  1/267 (0.37%) 
Stridor  1  0/109 (0.00%)  1/267 (0.37%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  0/109 (0.00%)  1/267 (0.37%) 
Skin ulcer  1  0/109 (0.00%)  1/267 (0.37%) 
Surgical and medical procedures     
Catheter placement  1  0/109 (0.00%)  1/267 (0.37%) 
Vascular disorders     
Aortic occlusion  1  0/109 (0.00%)  1/267 (0.37%) 
Hypotension  1  2/109 (1.83%)  0/267 (0.00%) 
Peripheral artery thrombosis  1  1/109 (0.92%)  0/267 (0.00%) 
Shock  1  1/109 (0.92%)  0/267 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Standard of Care Chemotherapy Blinatumomab
Affected / at Risk (%) Affected / at Risk (%)
Total   105/109 (96.33%)   250/267 (93.63%) 
Blood and lymphatic system disorders     
Anaemia  1  46/109 (42.20%)  69/267 (25.84%) 
Febrile neutropenia  1  36/109 (33.03%)  48/267 (17.98%) 
Neutropenia  1  31/109 (28.44%)  51/267 (19.10%) 
Thrombocytopenia  1  32/109 (29.36%)  47/267 (17.60%) 
Cardiac disorders     
Sinus tachycardia  1  6/109 (5.50%)  15/267 (5.62%) 
Tachycardia  1  10/109 (9.17%)  18/267 (6.74%) 
Gastrointestinal disorders     
Abdominal pain  1  19/109 (17.43%)  15/267 (5.62%) 
Constipation  1  28/109 (25.69%)  34/267 (12.73%) 
Diarrhoea  1  38/109 (34.86%)  58/267 (21.72%) 
Dyspepsia  1  7/109 (6.42%)  10/267 (3.75%) 
Haemorrhoids  1  6/109 (5.50%)  7/267 (2.62%) 
Nausea  1  46/109 (42.20%)  51/267 (19.10%) 
Proctalgia  1  7/109 (6.42%)  2/267 (0.75%) 
Stomatitis  1  14/109 (12.84%)  17/267 (6.37%) 
Vomiting  1  26/109 (23.85%)  31/267 (11.61%) 
General disorders     
Asthenia  1  11/109 (10.09%)  19/267 (7.12%) 
Chest pain  1  6/109 (5.50%)  6/267 (2.25%) 
Chills  1  12/109 (11.01%)  19/267 (7.12%) 
Fatigue  1  14/109 (12.84%)  34/267 (12.73%) 
Mucosal inflammation  1  14/109 (12.84%)  9/267 (3.37%) 
Oedema peripheral  1  16/109 (14.68%)  38/267 (14.23%) 
Pain  1  6/109 (5.50%)  16/267 (5.99%) 
Pyrexia  1  48/109 (44.04%)  153/267 (57.30%) 
Immune system disorders     
Cytokine release syndrome  1  0/109 (0.00%)  35/267 (13.11%) 
Hypogammaglobulinaemia  1  1/109 (0.92%)  16/267 (5.99%) 
Infections and infestations     
Bacteraemia  1  6/109 (5.50%)  3/267 (1.12%) 
Oral herpes  1  9/109 (8.26%)  15/267 (5.62%) 
Pneumonia  1  14/109 (12.84%)  7/267 (2.62%) 
Sinusitis  1  6/109 (5.50%)  5/267 (1.87%) 
Upper respiratory tract infection  1  1/109 (0.92%)  19/267 (7.12%) 
Investigations     
Alanine aminotransferase increased  1  11/109 (10.09%)  24/267 (8.99%) 
Aspartate aminotransferase increased  1  10/109 (9.17%)  15/267 (5.62%) 
Blood bilirubin increased  1  9/109 (8.26%)  10/267 (3.75%) 
Neutrophil count decreased  1  11/109 (10.09%)  10/267 (3.75%) 
Platelet count decreased  1  13/109 (11.93%)  17/267 (6.37%) 
White blood cell count decreased  1  6/109 (5.50%)  13/267 (4.87%) 
Metabolism and nutrition disorders     
Decreased appetite  1  15/109 (13.76%)  18/267 (6.74%) 
Hyperglycaemia  1  9/109 (8.26%)  20/267 (7.49%) 
Hypoalbuminaemia  1  11/109 (10.09%)  13/267 (4.87%) 
Hypocalcaemia  1  9/109 (8.26%)  10/267 (3.75%) 
Hypokalaemia  1  30/109 (27.52%)  45/267 (16.85%) 
Hypomagnesaemia  1  18/109 (16.51%)  28/267 (10.49%) 
Hypophosphataemia  1  6/109 (5.50%)  11/267 (4.12%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  5/109 (4.59%)  16/267 (5.99%) 
Back pain  1  10/109 (9.17%)  33/267 (12.36%) 
Bone pain  1  8/109 (7.34%)  29/267 (10.86%) 
Myalgia  1  6/109 (5.50%)  19/267 (7.12%) 
Pain in extremity  1  8/109 (7.34%)  25/267 (9.36%) 
Nervous system disorders     
Dizziness  1  8/109 (7.34%)  18/267 (6.74%) 
Headache  1  32/109 (29.36%)  77/267 (28.84%) 
Tremor  1  0/109 (0.00%)  26/267 (9.74%) 
Psychiatric disorders     
Anxiety  1  6/109 (5.50%)  13/267 (4.87%) 
Insomnia  1  10/109 (9.17%)  28/267 (10.49%) 
Renal and urinary disorders     
Acute kidney injury  1  6/109 (5.50%)  8/267 (3.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  6/109 (5.50%)  39/267 (14.61%) 
Dyspnoea  1  8/109 (7.34%)  15/267 (5.62%) 
Epistaxis  1  9/109 (8.26%)  16/267 (5.99%) 
Oropharyngeal pain  1  7/109 (6.42%)  13/267 (4.87%) 
Skin and subcutaneous tissue disorders     
Petechiae  1  6/109 (5.50%)  7/267 (2.62%) 
Rash  1  13/109 (11.93%)  19/267 (7.12%) 
Vascular disorders     
Hypertension  1  9/109 (8.26%)  17/267 (6.37%) 
Hypotension  1  11/109 (10.09%)  32/267 (11.99%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
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
Name/Title: Study Director
Organization: Amgen Inc.
Phone: 866-572-6436
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02013167     History of Changes
Other Study ID Numbers: 00103311
2013-000536-10 ( EudraCT Number )
First Submitted: December 3, 2013
First Posted: December 17, 2013
Results First Submitted: July 12, 2017
Results First Posted: August 9, 2017
Last Update Posted: November 28, 2018