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Study of Efficacy and Safety of CTL019 in Pediatric ALL Patients (ENSIGN)

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: NCT02228096
Recruitment Status : Completed
First Posted : August 28, 2014
Results First Posted : November 23, 2020
Last Update Posted : November 23, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions B-cell Acute Lymphoblastic Leukemia
Relapsed B-cell Acute Lymphoblastic Leukemia
Refractory B-cell Acute Lymphoblastic Leukemia
Intervention Biological: CTL019 T-cells
Enrollment 75
Recruitment Details Patients were recruited between 14-Aug-2014 (FPFV) and 22-Sep-2017 (LPFV). At the time of LPLV (24-May-2019), the sponsor had decided to transfer all ongoing patients to a separate long-term follow-up study to complete the planned 15 years of follow-up. These patients are designated with the reason for discontinuation as "terminated by sponsor".
Pre-assignment Details "Enrolled" means all eligibility criteria were met and apheresis was accepted by the manufacturing facility. Patients could discontinue the trial after enrollment and prior to tisagenlecleucel infusion. Although 75 patients were enrolled, only 64 were infused as 11 discontinued prior to infusion.
Arm/Group Title Tisagenlecleucel (CTL019) - All Participants
Hide Arm/Group Description Pediatric participants with r/r B-cell who were infused with tisagenlecleucel
Period Title: Overall Study
Started 75
Enrolled Into Long-term f/u Protocol 31
Enrolled But Not Infused [1] 11
Enrolled and Infused 64
Completed 4 [2]
Not Completed 71
Reason Not Completed
Study terminated by Sponsor             24
Lack of Efficacy             18
Death             12
Physician Decision             3
Subject/guardian decision             2
New therapy for study indication             1
Enrolled, not infused             11
[1]
Enrolled means all eligibility criteria were met & apheresis was accepted by manufacturing facility
[2]
Completed = study follow-up completed
Arm/Group Title Tisagenlecleucel (CTL019) - All Participants Not Infused Total
Hide Arm/Group Description Pediatric participants with r/r B-cell who were infused with tisagenlecleucel Pediatric patients with r/r B-cell who were enrolled in the study but not infused with tisagenlecleucel Total of all reporting groups
Overall Number of Baseline Participants 64 11 75
Hide Baseline Analysis Population Description
Enrolled Set: All participants who met all the inclusion/exclusion criteria, and whose apheresis product is received and accepted by the manufacturing facilty
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 64 participants 11 participants 75 participants
12.4  (5.16) 15.2  (5.44) 12.8  (5.26)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 64 participants 11 participants 75 participants
Female
34
  53.1%
1
   9.1%
35
  46.7%
Male
30
  46.9%
10
  90.9%
40
  53.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
White Number Analyzed 64 participants 11 participants 75 participants
52 8 60
Asian Number Analyzed 64 participants 11 participants 75 participants
5 1 6
Other Number Analyzed 64 participants 11 participants 75 participants
7 2 9
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 64 participants 11 participants 75 participants
43.7  (20.10) 86.2  (41.52) 47.3  (25.25)
Karnofsky/Lansky performance status   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
100 Number Analyzed 64 participants 0 participants 64 participants
18
  28.1%
18
  28.1%
90 Number Analyzed 64 participants 0 participants 64 participants
28
  43.8%
28
  43.8%
80 Number Analyzed 64 participants 0 participants 64 participants
13
  20.3%
13
  20.3%
70 Number Analyzed 64 participants 0 participants 64 participants
2
   3.1%
2
   3.1%
60 Number Analyzed 64 participants 0 participants 64 participants
1
   1.6%
1
   1.6%
50 Number Analyzed 64 participants 0 participants 64 participants
2
   3.1%
2
   3.1%
less than 50 Number Analyzed 64 participants 0 participants 64 participants
0
   0.0%
0
   0.0%
[1]
Measure Description: Karnofsky/Lansky performance status helps determine the functional status of a recipient. This status is a critical data field that has been determined to be essential for all outcome-based analyses. Karnofsky Scale: designed for recipients aged 16 years & older; Lansky Scale: designed for recipients 1 year old to less than 16 years old. The Karnofsky/Lansky performances are based from 100 to 0, where 100 is "perfect" health & 0 is death. The scale: Able to carry on normal activity, no special care needed (80- 100); Mild to moderate restriction (50-70); Moderate to severe restriction (10- 40).
[2]
Measure Analysis Population Description: FAS = All subjects who received an infusion of tisagenlecleucel
1.Primary Outcome
Title Overall Remission Rate (ORR) Per Independent Review Committee (IRC) (for ALL Participants)
Hide Description ORR is defined as the percentage of participants with a best overall disease response of complete remission (CR) or Complete remission with incomplete blood count recovery (CRi), where the best overall disease response is defined as the best disease response recorded from CTL019 infusion until the start of new anticancer therapy. Best response was assigned in the following order: CR, CRi, CR or CRi with residual mediastinal disease, No response and Unknown.
Time Frame within 6 months after CTL019 infusion
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set (EAS): A subset of all infused patients who were treated with CTL019 at least 6 months prior to the clinical data cutoff. In the final analysis, it is identical to the FAS
Arm/Group Title Tisagenlecleucel (CTL019) - All Participants
Hide Arm/Group Description:
Pediatric participants with r/r B-cell who were infused with tisagenlecleucel
Overall Number of Participants Analyzed 64
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
70.3
(57.6 to 81.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tisagenlecleucel (CTL019) - All Participants
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Clopper-Pearson
Comments [Not Specified]
2.Primary Outcome
Title Overall Remission Rate (ORR) Per Local Investigator Assessment (for Lymphoblastic Lymphoma Patients Only)
Hide Description Overall Remission Rate (ORR), which includes Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi), as determined by assessments of peripheral blood, bone marrow, CNS symptoms, physical exam (PE) and cerebrospinal fluid (CSF). This primary endpoint was based on the local investigator assessment. No participants with lymphoblastic lymphoma were infused in this study.
Time Frame 6 months after CTL019
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set (EAS): A subset of all infused patients who were treated with CTL019 at least 6 months prior to the clinical data cutoff. In the final analysis, it is identical to the FAS. No patients with Lymphoblastic Lymphoma were enrolled in this trial, hence there is no data to report.
Arm/Group Title Tisagenlecleucel (CTL019) - Local Assessment
Hide Arm/Group Description:
Pediatric participants with r/r B-cell ALL
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Percentage of Participants With Clinical Response Without Stem Cell Transplantation (SCT) at Month 6 - Per IRC Assessment
Hide Description Evaluate the percentage of participants who achieved CR or CRi at Month 6 without SCT between tisagenlecleucel infusion and Month 6 response assessment.
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set (EAS): A subset of all infused patients who were treated with CTL019 at least 6 months prior to the clinical data cutoff. In the final analysis, it is identical to the FAS.
Arm/Group Title Tisagenlecleucel (CTL019) - IRC Assessment
Hide Arm/Group Description:
Pediatric participants with r/r B-cell ALL
Overall Number of Participants Analyzed 64
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
53.1
(40.2 to 65.7)
4.Secondary Outcome
Title Percentage of Subjects Who Achieved CR or CRi and Then Proceeded to SCT While in Remission Prior to Month 6 Response - Per IRC Assessment
Hide Description Evaluate the percentage of subjects who achieved CR or CRi and then proceeded to SCT while in remission prior to Month 6 response assessment.
Time Frame prior to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set (EAS): A subset of all infused patients who were treated with CTL019 at least 6 months prior to the clinical data cutoff. In the final analysis, it is identical to the FAS.
Arm/Group Title Tisagenlecleucel (CTL019) - Per IRC Assessment
Hide Arm/Group Description:
Pediatric participants with r/r B-cell ALL
Overall Number of Participants Analyzed 64
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
7.8
(2.6 to 17.3)
5.Secondary Outcome
Title Duration of Remission (DOR) Per Local and IRC Assessment
Hide Description DOR is the time from achievement of CR or CRi, whichever occurs first, to relapse or death due to ALL
Time Frame From CR or CRi to relapse or death up to 60 months
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set (EAS): A subset of all infused patients who were treated with CTL019 at least 6 months prior to the clinical data cutoff. In the final analysis, it is identical to the FAS.
Arm/Group Title Tisagenlecleucel (CTL019) - Local Assessment Tisagenlecleucel (CTL019) - IRC Assessment
Hide Arm/Group Description:
Pediatric participants with r/r B-cell ALL
Pediatric participants with r/r B-cell ALL
Overall Number of Participants Analyzed 64 64
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(13.6 to NA)
NA [1] 
(13.6 to NA)
[1]
N/A = median DOR was not reached as there were not enough participants with DOR events
6.Secondary Outcome
Title Percentage of Participants With CR or CRi With Minimum Residual Disease (MRD) Negative Bone Marrow 6 Months After CTL019 Infusion
Hide Description Percentage of participants with best overall response (BOR) of CR or CRi with MRD negative bone marrow status 6 months after CTL019 infusion among all participants who achieved CR or CRi per Local Investigator & IRC assessment
Time Frame within 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set (EAS): A subset of all infused patients who were treated with CTL019 at least 6 months prior to the clinical data cutoff. In the final analysis, it is identical to the FAS.
Arm/Group Title Tisagenlecleucel (CTL019) - Local Assessment Tisagenlecleucel (CTL019) - IRC Assessment
Hide Arm/Group Description:
Pediatric participants with r/r B-cell ALL
Pediatric participants with r/r B-cell ALL
Overall Number of Participants Analyzed 64 64
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
67.2
(54.3 to 78.4)
67.2
(54.3 to 78.4)
7.Secondary Outcome
Title Relapse-free Survival (RFS) for Responders Per Local and IRC Assessment
Hide Description RFS is the time from achievement of CR or CRi whichever occurs first to relapse or death due to any cause during CR or CRi.
Time Frame 60 Months
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set (EAS): A subset of all infused patients who were treated with CTL019 at least 6 months prior to the clinical data cutoff. In the final analysis, it is identical to the FAS.
Arm/Group Title Tisagenlecleucel (CTL019) - Local Assessment Tisagenlecleucel (CTL019) - IRC Assessment
Hide Arm/Group Description:
Pediatric participants with r/r B-cell ALL
Pediatric participants with r/r B-cell ALL
Overall Number of Participants Analyzed 45 45
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(13.6 to NA)
NA [1] 
(13.6 to NA)
[1]
N/A = median RFS was not reached as there were not enough participants with RFS events
8.Secondary Outcome
Title Event-free Survival (EFS) Per Local and IRC Assessment
Hide Description EFS is the time from date of CTL019 infusion to the earliest of death, relapse or treatment failure. Treatment failure is defined as "no response" in the study and discontinuation from the study due to any of the following reasons: death, AE, lack of efficacy, new anticancer therapy.
Time Frame 60 Months
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: All subjects who received an infusion of CTL019
Arm/Group Title Tisagenlecleucel (CTL019) - Local Assessment Tisagenlecleucel (CTL019) - IRC Assessment
Hide Arm/Group Description:
Pediatric participants with r/r B-cell ALL
Pediatric participants with r/r B-cell ALL
Overall Number of Participants Analyzed 64 64
Median (95% Confidence Interval)
Unit of Measure: months
15.6 [1] 
(6.4 to NA)
15.6 [1] 
(6.4 to NA)
[1]
N/A = not estimable because there were not enough participants who had an EFS event to estimate the upper limit of the median EFS
9.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS is the time from date of CTL019 infusion to the date of death due to any reason
Time Frame 60 Months
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: All subjects who received an infusion of CTL019
Arm/Group Title Tisagenlecleucel (CTL019) - All Participants
Hide Arm/Group Description:
Pediatric participants with r/r B-cell who were infused with tisagenlecleucel
Overall Number of Participants Analyzed 64
Median (95% Confidence Interval)
Unit of Measure: months
29.9
(15.1 to 42.4)
10.Secondary Outcome
Title Secondary Outcome: Percentage of Participants Attaining CR or CRi With MRD Negative Bone Marrow Status at Day 28 +/- 4 Days After CTL019 Infusion
Hide Description Percentage of participants attaining CR or CRi with MRD negative bone marrow status at Day 28 +/- 4 days after CTL019 infusion per Local Investigator and IRC assessment. BM MRD were only collected and measured only within responders.
Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set (EAS): A subset of all infused patients who were treated with CTL019 at least 6 months prior to the clinical data cutoff. In the final analysis, it is identical to the FAS. BM MRD were only collected and measured only within responders.
Arm/Group Title Tisagenlecleucel (CTL019) - Local Assessment Tisagenlecleucel (CTL019) - IRC Assessment
Hide Arm/Group Description:
Pediatric participants with r/r B-cell ALL
Pediatric participants with r/r B-cell ALL
Overall Number of Participants Analyzed 64 64
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
With BM MRD -ve: i.e. MRD% < 0.01%
71.9
(59.2 to 82.4)
71.9
(59.2 to 82.4)
With BM 0.01% <= MRD% < 5%
1.6 [1] 
(NA to NA)
1.6 [1] 
(NA to NA)
With BM MRD% >= 5%
1.6 [2] 
(NA to NA)
1.6 [2] 
(NA to NA)
BM MRD not available
6.3 [3] 
(NA to NA)
6.3 [3] 
(NA to NA)
[1]
N/A: only 1 participant with BM MRD to calculate meaningful confidence interval (CI)
[2]
N/A: only 1 participant with BM MRD to calculate meaningful CI
[3]
N/A: few participants with BM MRD to provide meaningful CI
11.Secondary Outcome
Title CTL019 Transgene Levels by qPCR CTL019 Cells by in qPCR Blood and Bone Marrow
Hide Description Characterize the in vivo cellular pharmacokinetic (PK) profile (levels,persistence, trafficking) of CTL019 cells in target tissues
Time Frame Enrollment; D1; D4; D7; D11; D14; D21; D28; M3; M6; M9, M12; M18; M24, M30, M36, M42, M48 for transgene levels in blood; Screening, D28, M3, M6 for transgene levels in bone marrow
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Analysis Set (PAS): A subset of FAS who have at least one sample providing evaluable pharmacokinetic (PK) data
Arm/Group Title CR/CRi No Response (NR) Unknown
Hide Arm/Group Description:
Participants had Complete remission (CR)/Complete remission with incomplete blood count recovery (CRi)
No response was defined as failure to attain the criteria needed for any response categories or relapse
unknown was assigned in case the baseline assessment or the response assessment was not done, incomplete, indeterminate or not performed within the respective time frame.
Overall Number of Participants Analyzed 52 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: copies/ug DNA
Enrollment blood Number Analyzed 49 participants 6 participants 5 participants
NA [1] 
(NA%)
NA [1] 
(NA%)
NA [1] 
(NA%)
Day 1 (D1): blood Number Analyzed 41 participants 4 participants 6 participants
3680
(344.3%)
3190
(348.6%)
2440
(220.6%)
D4: blood Number Analyzed 48 participants 6 participants 6 participants
234
(197.8%)
48.8
(282.4%)
88.0
(71.0%)
D7: blood Number Analyzed 51 participants 6 participants 6 participants
4460
(616.2%)
231
(499.1%)
402
(114.7%)
D11: blood Number Analyzed 34 participants 4 participants 4 participants
21200
(262.3%)
423
(52.7%)
1920
(8318.1%)
D14: blood Number Analyzed 49 participants 6 participants 5 participants
12500
(292.1%)
1600
(337.1%)
42835.8
(9060%)
D21: blood Number Analyzed 49 participants 6 participants 5 participants
3720
(480.5%)
7750
(334.5%)
1050
(220743.9%)
D28: blood Number Analyzed 52 participants 6 participants 3 participants
1360
(650.3%)
2770
(684.8%)
515
(244650713.9%)
Month 3 (M3): blood Number Analyzed 49 participants 2 participants 2 participants
220
(224.3%)
690 [2] 
(NA%)
564 [2] 
(NA%)
Month M6: blood Number Analyzed 40 participants 1 participants 1 participants
146
(157.5%)
NA [3] 
(NA%)
127 [2] 
(NA%)
Month M9: blood Number Analyzed 30 participants 0 participants 0 participants
117
(179.3%)
Month M12: blood Number Analyzed 30 participants 0 participants 0 participants
113
(312.4%)
Month M18: blood Number Analyzed 18 participants 0 participants 0 participants
87.2
(200.3%)
Month M24: blood Number Analyzed 15 participants 0 participants 0 participants
92.7
(160.5%)
Month M30: blood Number Analyzed 5 participants 0 participants 0 participants
59.9
(150.0%)
Month M36: blood Number Analyzed 3 participants 0 participants 0 participants
10.7
(19.9%)
Month M42: blood Number Analyzed 2 participants 0 participants 0 participants
35.3 [2] 
(NA%)
Month M48: blood Number Analyzed 1 participants 0 participants 0 participants
NA [4] 
(NA%)
Screening: Bone marrow (BM) Number Analyzed 47 participants 6 participants 6 participants
NA [5] 
(NA%)
NA [5] 
(NA%)
NA [5] 
(NA%)
D28 BM Number Analyzed 50 participants 4 participants 4 participants
646
(1009.7%)
969
(166.8%)
615
(4763885.9%)
M3 BM Number Analyzed 40 participants 0 participants 2 participants
179
(182.5%)
542 [2] 
(NA%)
M6 BM Number Analyzed 32 participants 1 participants 0 participants
133
(121.7%)
35.3 [2] 
(NA%)
[1]
N/A: No CTL019 was infused at the enrollment
[2]
N/A = not estimable because too few participants to calculate Geometric CV
[3]
N/A = not estimable because too few participants to calculate Geometric CV; also, the geometric mean was not applicable for NR group at Month 6 as the arithmetic mean was zero
[4]
NA = geometric mean is not estimable because the CTL019 transgene level for the only one patient is 0.
[5]
N/A = No CTL019 was infused at screening
12.Secondary Outcome
Title Humoral Immunogenicity Interpretation by Day 28 Disease Response Per IRC (Anti-CTL019 Antibodies)
Hide Description Humoral immunogenicity was measured by anti-CTL019 antibodies in human serum using a flow cytometry method. (Prevalence and incidence of immunogenicity to CTL019)
Time Frame Baseline; Day 14; Day 28; Month 3; Month 6; Month 12; Month 24, Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set: All subjects who received an infusion of tisagenlecleucel
Arm/Group Title CR/CRi No Response Unknown
Hide Arm/Group Description:
Participants had Complete remission (CR)/Complete remission with incomplete blood count recovery (CRi)
No response was defined as failure to attain the criteria needed for any response categories or relapse
unknown was assigned in case the baseline assessment or the response assessment was not done, incomplete, indeterminate or not performed within the respective time frame.
Overall Number of Participants Analyzed 52 6 6
Measure Type: Number
Unit of Measure: Percentage of participants
Baseline: Positive 67.3 66.7 83.3
Day 14: Positive 84.6 100 83.3
Day 28: Positive 80.8 100 50.0
Month 3: Positive 75.0 16.7 33.3
Month 6: Positive 63.5 16.7 16.7
Month 12: Positive 46.2 0 0
Month 24: Positive 11.5 0 0
Month 36: Positive 9.6 0 0
13.Secondary Outcome
Title ORR by Low Baseline Bone Marrow Burden Within 6 Months Post CTL019 Infusion
Hide Description ORR within 6 months after infusion of CTL019 per Local & IRC assessment by baseline bone marrow tumor burden presence.
Time Frame Within 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
EAS: Efficacy Analysis Set (EAS): A subset of full analysis set (FAS) who were treated with CTL019 at least 6 months prior to the clinical data cutoff FAS: All subjects who received an infusion of CTL019. Data is based on data cut-off date of 6-Oct-2017, with only 42 participants and 12 having a low bone marrow tumor burden at enrollment.
Arm/Group Title Tisagenlecleucel (CTL019) - Local Assessment Tisagenlecleucel (CTL019) - IRC Assessment
Hide Arm/Group Description:
Pediatric participants with r/r B-cell ALL
Pediatric participants with r/r B-cell ALL
Overall Number of Participants Analyzed 12 12
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
83.3
(51.6 to 97.9)
83.3
(51.6 to 97.9)
14.Secondary Outcome
Title ORR by High Baseline Bone Marrow Burden Within 6 Months Post CTL019 Infusion
Hide Description ORR within 6 months after infusion of CTL019 per Local Investigator & IRC assessment by high baseline bone marrow tumor burden presence.
Time Frame Within 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
EAS: Efficacy Analysis Set (EAS): A subset of full analysis set (FAS) who were treated with CTL019 at least 6 months prior to the clinical data cutoff FAS: All subjects who received an infusion of CTL019. Data is based on data cut-off date of 6-Oct-2017, with only 42 participants and 30 having a high bone marrow tumor burden at enrollment
Arm/Group Title Tisagenlecleucel (CTL019) - Local Assessment Tisagenlecleucel (CTL019) - IRC Assessment
Hide Arm/Group Description:
Pediatric participants with r/r B-cell ALL
Pediatric participants with r/r B-cell ALL
Overall Number of Participants Analyzed 30 30
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
63.3
(43.9 to 80.1)
63.3
(43.9 to 80.1)
15.Secondary Outcome
Title ORR by Baseline Extramedullary Disease Presence of Yes Within 6 Months Post CTL019 Infusion
Hide Description ORR within 6 months after infusion of CTL019 per Local Investigator & IRC assessment by baseline extramedullary disease presence of Yes.
Time Frame Within 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
EAS: Efficacy Analysis Set (EAS): A subset of full analysis set (FAS) who were treated with CTL019 at least 6 months prior to the clinical data cutoff FAS: All subjects who received an infusion of CTL019. Data is based on data cut-off date of 6-Oct-2017, with only 42 participants and 2 participants having a baseline extramedullary presence.
Arm/Group Title Tisagenlecleucel (CTL019) - Local Assessment Tisagenlecleucel (CTL019) - IRC Assessment
Hide Arm/Group Description:
Pediatric participants with r/r B-cell ALL
Pediatric participants with r/r B-cell ALL
Overall Number of Participants Analyzed 2 2
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
100 [1] 
(NA to NA)
100 [1] 
(NA to NA)
[1]
N/A: no confidence interval for 100% response
16.Secondary Outcome
Title ORR by Baseline Extramedullary Disease Presence of No Within 6 Months Post CTL019 Infusion
Hide Description ORR within 6 months after infusion of CTL019 per Local Investigator & IRC assessment by baseline extramedullary disease presence of No.
Time Frame Within 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
EAS: Efficacy Analysis Set (EAS): A subset of full analysis set (FAS) who were treated with CTL019 at least 6 months prior to the clinical data cutoff FAS: All subjects who received an infusion of CTL019. Data is based on data cut-off date of 6-Oct-2017, with only 42 participants and 40 participants having no baseline extramedullary presence.
Arm/Group Title Tisagenlecleucel (CTL019) - Local Assessment Tisagenlecleucel (CTL019) - IRC Assessment
Hide Arm/Group Description:
Pediatric participants with r/r B-cell ALL
Pediatric participants with r/r B-cell ALL
Overall Number of Participants Analyzed 40 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
67.5
(50.9 to 81.4)
67.5
(50.9 to 81.4)
17.Secondary Outcome
Title Bone Marrow (BM) Minimum Residual Disease (MRD) Status by Flow Cytometry Within 6 Months Post CTL019 Infusion by High Baseline Bone Marrow Tumor Burden
Hide Description BM MRD status was by Local Investigator and IRC assessment within 6 months after infusion of CTL019 by baseline bone marrow tumor burden. BM MRD were collected and measured only within responders.
Time Frame Within 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set: A subset of FAS treated with CTL019 at least 6 months prior to the clinical data cutoff FAS: All subjects who received an infusion of CTL019. Data is based on cut-off date of 6-Oct-2017, with only 42 participants and 30 having a high baseline bone marrow tumor burden. BM MRD were collected and measured only within responders
Arm/Group Title Tisagenlecleucel (CTL019) - Local Assessment Tisagenlecleucel (CTL019) - IRC Assessment
Hide Arm/Group Description:
Pediatric participants with r/r B-cell ALL
Pediatric participants with r/r B-cell ALL
Overall Number of Participants Analyzed 30 30
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Had BOR of CR/CRi with BM MRD -ve (MRD%< 0.01%)
56.7
(37.4 to 74.5)
56.7
(37.4 to 74.5)
Had BOR of CR/CRi with BM 0.01% <= MRD% < 5%
6.7 [1] 
(NA to NA)
6.7 [1] 
(NA to NA)
[1]
N/A = too few participants to calculate a meaningful CI
18.Secondary Outcome
Title Bone Marrow MRD Status Was by Flow Cytometry Within 6 Months Post CTL019 Infusion by Low Baseline Bone Marrow Tumor Burden
Hide Description BM MRD status was per Local Investigator and IRC assessment within 6 months after infusion of CTL019 by low baseline bone marrow tumor burden. BM MRD were collected and measured only within responders.
Time Frame Within 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set: A subset of FAS treated with CTL019 at least 6 months prior to the clinical data cutoff FAS: All subjects who received an infusion of CTL019. Data is based on cut-off date of 6-Oct-2017, with only 42 participants and 12 having a high baseline bone marrow tumor burden. BM MRD were collected and measured only within responders
Arm/Group Title Tisagenlecleucel (CTL019) - Local Assessment Tisagenlecleucel (CTL019) - IRC Assessment
Hide Arm/Group Description:
Pediatric participants with r/r B-cell ALL
Pediatric participants with r/r B-cell ALL
Overall Number of Participants Analyzed 12 12
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
83.3
(51.6 to 97.9)
83.3
(51.6 to 97.9)
19.Secondary Outcome
Title Bone Marrow MRD Status by Flow Cytometry Within 6 Months Post CTL019 Infusion by Baseline Extramedullary Disease Presence: Yes
Hide Description BM MRD status was by Local Investigator and IRC assessment within 6 months after infusion pf CTL019 by baseline extramedullary disease presence of Yes. BM MRD were collected and measured only within responders.
Time Frame Within 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set: A subset of FAS treated with CTL019 at least 6 months prior to the clinical data cutoff. FAS: All subjects who received an infusion of CTL019. Data is based on cut-off date of 6-Oct-2017, with only 42 participants & 2 having a BL extramedullary disease presence of Yes. BM MRD were collected & measured only within responders.
Arm/Group Title Tisagenlecleucel (CTL019) - Local Assessment Tisagenlecleucel (CTL019) - IRC Assessment
Hide Arm/Group Description:
Pediatric participants with r/r B-cell ALL
Pediatric participants with r/r B-cell ALL
Overall Number of Participants Analyzed 2 2
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
100
(15.8 to 100)
100
(15.8 to 100)
20.Secondary Outcome
Title Bone Marrow MRD Status by Flow Cytometry Within 6 Months Post CTL019 Infusion by Baseline Extramedullary Disease Presence: No
Hide Description BM MRD status WAS per Local Investigator and IRC assessment within 6 months after infusion pf CTL019 by baseline extramedullary disease presence of No. BM MRD were collected and measured only within responders.
Time Frame Within 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set: A subset of FAS treated with CTL019 at least 6 months prior to the clinical data cutoff. FAS: All subjects who received an infusion of CTL019. Data is based on cut-off date of 6-Oct-2017, with only 42 participants & 40 having a BL extramedullary disease presence of No. BM MRD were collected & measured only within responders.
Arm/Group Title Tisagenlecleucel (CTL019) - Local Assessment Tisagenlecleucel (CTL019) - IRC Assessment
Hide Arm/Group Description:
Pediatric participants with r/r B-cell ALL
Pediatric participants with r/r B-cell ALL
Overall Number of Participants Analyzed 40 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
With BM MRD -ve (MRD%< 0.01%)
62.5
(45.8 to 77.3)
62.5
(45.8 to 77.3)
With bone marrow 0.01% <= MRD% < 5%
5.0 [1] 
(NA to NA)
5.0 [1] 
(NA to NA)
[1]
N/A = too few participants to calculate CI
21.Secondary Outcome
Title Duration of Remission (DoR) Censoring Hematopoietic Stem Cell Transplantation (HSCT) by Low Baseline Bone Marrow Tumor Burden
Hide Description DoR per Local Investigator & IRC assessment by low baseline marrow tumor burden
Time Frame Within 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
EAS: Efficacy Analysis Set (EAS): A subset of full analysis set (FAS) who were treated with CTL019 at least 6 months prior to the clinical data cutoff FAS: All subjects who received an infusion of CTL019. Data is based on data cut-off date of 6-Oct-2017, with only 42 participants and 12 having a low baseline marrow tumor burden
Arm/Group Title Tisagenlecleucel (CTL019) - Local Assessment Tisagenlecleucel (CTL019) - IRC Assessment
Hide Arm/Group Description:
Pediatric participants with r/r B-cell ALL
Pediatric participants with r/r B-cell ALL
Overall Number of Participants Analyzed 12 12
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(5.4 to NA)
NA [1] 
(5.4 to NA)
[1]
N/A = median DoR was not reached as there were not enough participants with DoR events
22.Secondary Outcome
Title Duration of Remission (DoR) Censoring HSCT by High Baseline Bone Marrow Tumor Burden
Hide Description DoR per Local Investigator & IRC assessment by high baseline bone marrow tumor burden
Time Frame Within 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
EAS: Efficacy Analysis Set (EAS): A subset of full analysis set (FAS) who were treated with CTL019 at least 6 months prior to the clinical data cutoff FAS: All subjects who received an infusion of CTL019. Data is based on data cut-off date of 6-Oct-2017, with only 42 participants and 30 having a high baseline marrow tumor burden
Arm/Group Title Tisagenlecleucel (CTL019) - Local Assessment Tisagenlecleucel (CTL019) - IRC Assessment
Hide Arm/Group Description:
Pediatric participants with r/r B-cell ALL
Pediatric participants with r/r B-cell ALL
Overall Number of Participants Analyzed 30 30
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(5.3 to NA)
NA [1] 
(5.3 to NA)
[1]
N/A = median DoR was not reached as there were not enough participants with DoR events
23.Secondary Outcome
Title Duration of Remission (DoR) Censoring HSCT by Baseline Extramedullary Disease Presence: Yes
Hide Description DoR per Local Investigator & IRC assessment by baseline extramedullary disease presence of Yes.
Time Frame Within 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
EAS: Efficacy Analysis Set (EAS): A subset of full analysis set (FAS) who were treated with CTL019 at least 6 months prior to the clinical data cutoff FAS: All subjects who received an infusion of CTL019. Data is based on data cut-off date of 6-Oct-2017, with only 42 participants and 2 having a baseline extramedullary disease presence of Yes
Arm/Group Title Tisagenlecleucel (CTL019) - Local Assessment Tisagenlecleucel (CTL019) - IRC Assessment
Hide Arm/Group Description:
Pediatric participants with r/r B-cell ALL
Pediatric participants with r/r B-cell ALL
Overall Number of Participants Analyzed 2 2
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(3.4 to NA)
NA [2] 
(3.4 to NA)
[1]
N/A = median DoR was not reached as there were not enough participants with D0R events
[2]
N/A = median DoR was not reached as there were not enough participants with DoR events
24.Secondary Outcome
Title Duration of Remission (DoR) Censoring HSCT by Baseline Extramedullary Disease Presence: No
Hide Description DoR per Local Investigator & IRC assessment by baseline extramedullary disease presence of No
Time Frame Within 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
EAS: Efficacy Analysis Set (EAS): A subset of full analysis set (FAS) who were treated with CTL019 at least 6 months prior to the clinical data cutoff FAS: All subjects who received an infusion of CTL019. Data is based on data cut-off date of 6-Oct-2017, with only 42 participants and 40 having a baseline extramedullary disease presence of No
Arm/Group Title Tisagenlecleucel (CTL019) - Local Assessment Tisagenlecleucel (CTL019) - IRC Assessment
Hide Arm/Group Description:
Pediatric participants with r/r B-cell ALL
Pediatric participants with r/r B-cell ALL
Overall Number of Participants Analyzed 40 40
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(5.9 to NA)
NA [1] 
(5.9 to NA)
[1]
N/A = median DOR was not reached as there were not enough participants with DOR events
25.Secondary Outcome
Title Participants Achieving Cellular Immunogenicity Net Response by Day 28 Response Per IRC
Hide Description Activation of T cells in PBMC collected from subjects in response to mCAR19 -derived peptides was used to assess the cellular immunogenicity against tisagenlecleucel. CD4 and CD8 T cell net responses (in %) were calculated for 2 non-overlapping CTL019 peptide pools (i.e., Pool 1 and Pool 2). (Lymphocyte subsets of B and T cells and description of associated safety events)
Time Frame Baseline; Day 14; Day 28; Month 3; Month 6; Month 12; Month 24, Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set: All subjects who received an infusion of tisagenlecleucel
Arm/Group Title CR/CRi No Response Unknown
Hide Arm/Group Description:
Participants had Complete remission (CR)/Complete remission with incomplete blood count recovery (CRi)
No response was defined as failure to attain the criteria needed for any response categories or relapse
unknown was assigned in case the baseline assessment or the response assessment was not done, incomplete, indeterminate or not performed within the respective time frame.
Overall Number of Participants Analyzed 52 6 6
Measure Type: Number
Unit of Measure: Percentage of participants
Baseline: Pool 1 CD3+ CD4+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
92.3 83.3 50.0
Day 14: Pool 1 CD3+ CD4+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
82.7 100 50.0
Day 28: Pool 1 CD3+ CD4+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
94.2 100 50.0
Month 3: Pool 1 CD3+ CD4+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
82.7 16.7 33.3
Month 6: Pool 1 CD3+ CD4+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
67.3 16.7 57.8
Month 12: Pool 1 CD3+ CD4+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
48.1 0 0
Month 24: Pool 1 CD3+ CD4+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
17.3 0 0
Month 36: Pool 1 CD3+ CD4+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
9.6 0 0
Baseline: Pool 2 CD3+ CD4+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
92.3 83.3 50.0
Day 14: Pool 2 CD3+ CD4+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
82.7 100 50.0
Day 28: Pool 2 CD3+ CD4+ IFNg+ ) Number Analyzed 52 participants 6 participants 6 participants
94.2 100 50.0
Month 3: Pool 2 CD3+ CD4+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
82.7 16.7 33.3
Month 6: Pool 2 CD3+ CD4+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
67.3 16.7 16.7
Month 12: Pool 2 CD3+ CD4+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
48.1 0 0
Month 24: Pool 2 CD3+ CD4+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
17.3 0 0
Month 36: Pool 2 CD3+ CD4+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
9.6 0 0
Baseline: Pool 1 CD3+ CD8+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
92.3 83.3 50.0
Day 14: Pool 1 CD3+ CD8+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
82.7 100 50.0
Day 28: Pool 1 CD3+ CD8+ IFNg+ Number Analyzed 41 participants 6 participants 2 participants
94.2 100 50.0
Month 3: Pool 1 CD3+ CD8+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
82.7 16.7 33.3
Month 6: Pool 1 CD3+ CD8+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
67.3 16.7 16.7
Month 12: Pool 1 CD3+ CD8+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
48.1 0 0
Month 24: Pool 1 CD3+ CD8+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
17.3 0 0
Month 36: Pool 1 CD3+ CD8+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
9.6 0 0
Baseline: Pool 2 CD3+ CD8+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
92.3 83.3 50.0
Day 14: Pool 2 CD3+ CD8+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
82.7 100 50.0
Day 28: Pool 2 CD3+ CD8+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
94.2 100 50.0
Month 3: Pool 2 CD3+ CD8+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
82.7 16.7 33.3
Month 6: Pool 2 CD3+ CD8+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
67.3 16.7 16.7
Month 12: Pool 2 CD3+ CD8+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
48.1 0 0
Month 24: Pool 2 CD3+ CD8+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
17.3 0 0
Month 36: Pool 2 CD3+ CD8+ IFNg+ Number Analyzed 52 participants 6 participants 6 participants
9.6 0 0
26.Secondary Outcome
Title Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: AUC0-28d and AUC0-84d
Hide Description Characterize the in vivo cellular pharmacokinetic (PK) profile. AUC0-28d and AUC0-84d is defined as the AUC from time zero to day 28 and 84 or other disease assessment days, in peripheral blood (% or copies/μg x days). Data was only reported for evaluable PK parameters. The Overall Number of Participants Analyzed represents all participants for which a baseline assessment was collected for this Outcome Measure, and therefore these participants did contribute data to this estimation parameter, whereas the Number Analyzed per Row represents the number of participants with data available at either 28 or 84 days.
Time Frame 0 - 28 days post-infusion for AUC0-28d and 0 - 84 days post-infusion for AUC0-84d
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Analysis Set (PAS): A subset of FAS who have at least one sample providing evaluable pharmacokinetic (PK) data.
Arm/Group Title CR/CRi No Response (NR) Unknown
Hide Arm/Group Description:
Participants had Complete remission (CR)/Complete remission with incomplete blood count recovery (CRi)
No response was defined as failure to attain the criteria needed for any response categories or relapse
unknown was assigned in case the baseline assessment or the response assessment was not done, incomplete, indeterminate or not performed within the respective time frame.
Overall Number of Participants Analyzed 52 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: copies/µg*days
AUC0-28d Number Analyzed 52 participants 3 participants 1 participants
261000
(199.8%)
151000
(71.7%)
617000 [1] 
(NA%)
AUC0-84d Number Analyzed 45 participants 2 participants 1 participants
368000
(182.9%)
443000
(79.9%)
1340000 [1] 
(NA%)
[1]
N/A = Too few participants to calculate geometric CV
27.Secondary Outcome
Title Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Cmax
Hide Description Characterize the in vivo cellular pharmacokinetic (PK) profile. Cmax is defined as the maximum (peak) observed in peripheral blood drug concentration after single dose administration (% or copies/μg).
Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Analysis Set (PAS): A subset of FAS who have at least one sample providing evaluable pharmacokinetic (PK) data
Arm/Group Title CR/CRi No Response (NR) Unknown
Hide Arm/Group Description:
Participants had Complete remission (CR)/Complete remission with incomplete blood count recovery (CRi)
No response was defined as failure to attain the criteria needed for any response categories or relapse
unknown was assigned in case the baseline assessment or the response assessment was not done, incomplete, indeterminate or not performed within the respective time frame.
Overall Number of Participants Analyzed 52 5 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: copies/µg
28300
(197.0%)
15100
(49.4%)
52500
(91.1%)
28.Secondary Outcome
Title Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Tmax
Hide Description Characterize the in vivo cellular pharmacokinetic (PK) profile. Tmax is defined as the time to reach maximum (peak) peripheral blood drug concentration after single dose administration (days)
Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Analysis Set (PAS): A subset of FAS who have at least one sample providing evaluable pharmacokinetic (PK) data
Arm/Group Title CR/CRi No Response (NR) Unknown
Hide Arm/Group Description:
Participants had Complete remission (CR)/Complete remission with incomplete blood count recovery (CRi)
No response was defined as failure to attain the criteria needed for any response categories or relapse
unknown was assigned in case the baseline assessment or the response assessment was not done, incomplete, indeterminate or not performed within the respective time frame.
Overall Number of Participants Analyzed 52 5 2
Median (Full Range)
Unit of Measure: days
9.84
(6.74 to 54.8)
20.0
(13.9 to 22.8)
11.9
(11.0 to 12.9)
29.Secondary Outcome
Title Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: T1/2
Hide Description Characterize the in vivo cellular pharmacokinetic (PK) profile. T1/2 is defined as the half-life associated with the disposition phase slopes (alpha, beta, gamma etc.) of a semi logarithmic concentration-time curve (days) in peripheral blood
Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Analysis Set (PAS): A subset of FAS who have at least one sample providing evaluable pharmacokinetic (PK) data
Arm/Group Title CR/CRi No Response (NR) Unknown
Hide Arm/Group Description:
Participants had Complete remission (CR)/Complete remission with incomplete blood count recovery (CRi)
No response was defined as failure to attain the criteria needed for any response categories or relapse
unknown was assigned in case the baseline assessment or the response assessment was not done, incomplete, indeterminate or not performed within the respective time frame.
Overall Number of Participants Analyzed 34 2 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: days
31.9
(415.1%)
4.36
(421.2%)
42.1 [1] 
(NA%)
[1]
N/A = with only 1 subject, geometric CV could not be calculated
30.Secondary Outcome
Title Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Clast
Hide Description Characterize the in vivo cellular pharmacokinetic (PK) profile. Clast is defined as the last observed quantifiable concentration in peripheral blood (% or copies/ug)
Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Analysis Set (PAS): A subset of FAS who have at least one sample providing evaluable pharmacokinetic (PK) data
Arm/Group Title CR/CRi No Response (NR) Unknown
Hide Arm/Group Description:
Participants had Complete remission (CR)/Complete remission with incomplete blood count recovery (CRi)
No response was defined as failure to attain the criteria needed for any response categories or relapse
unknown was assigned in case the baseline assessment or the response assessment was not done, incomplete, indeterminate or not performed within the respective time frame.
Overall Number of Participants Analyzed 52 5 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: copies/µg
223
(283.4%)
1980
(207.5%)
80.3 [1] 
(NA%)
[1]
N/A = with only 1 subject, geometric CV could not be calculated
31.Secondary Outcome
Title Peripheral Blood PK Parameters for Tisagenlecleucel Transgene Levels by qPCR, by Day 28 Disease Response by Local & IRC Assessment: Tlast
Hide Description Characterize the in vivo cellular pharmacokinetic (PK) profile. Tlast is defined as the time of last observed quantifiable concentration in peripheral blood (days)"
Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Analysis Set (PAS): A subset of FAS who have at least one sample providing evaluable pharmacokinetic (PK) data
Arm/Group Title CR/CRi No Response (NR) Unknown
Hide Arm/Group Description:
Participants had Complete remission (CR)/Complete remission with incomplete blood count recovery (CRi)
No response was defined as failure to attain the criteria needed for any response categories or relapse
unknown was assigned in case the baseline assessment or the response assessment was not done, incomplete, indeterminate or not performed within the respective time frame.
Overall Number of Participants Analyzed 52 5 1
Median (Full Range)
Unit of Measure: days
179
(17.8 to 921)
26.9
(26.7 to 96.1)
210
(210 to 210)
32.Secondary Outcome
Title CD19 Status of Bone Marrow/Blood Relapse in FAS Patients Who Achieved CR or CRi and Then Relapsed
Hide Description The CD19 status of bone marrow/blood relapse was categorized as follows: CD19 positive, CD19 dim, CD19 negative, CD19 positive/negative & CD19 unknown
Time Frame At time of relapse up to 60 months
Hide Outcome Measure Data
Hide Analysis Population Description
FAS patients who achieved CR & CRi and then relapsed. FAS: All subjects who received an infusion of CTL019
Arm/Group Title Tisagenlecleucel - FAS Pts Who Achieved CR/CRi & Then Relapsed
Hide Arm/Group Description:
Pediatric participants with r/r B-cell who were infused with tisagenlecleucel and then relapsed
Overall Number of Participants Analyzed 21
Measure Type: Number
Unit of Measure: Percentage of participants
CD19 status of BM/blood relapse:positive 22.2
CD19 status of BM/blood relapse: dim 5.6
CD19 status of BM/blood relapse: negative 16.7
CD19 status of BM/blood relapse: +ve/-ve 16.7
CD19 status of BM/blood relapse: Unknown 55.6
33.Secondary Outcome
Title Site of Initial Relapse Among FAS Patients Who Achieved CR/CRi and Then Relapsed
Hide Description This is the site of involvement of initial relapse after achieving a best overall response of CR/CRi.
Time Frame At time of relapse up to 60 months
Hide Outcome Measure Data
Hide Analysis Population Description
FAS patients who achieved CR & CRi and then relapsed. FAS: All subjects who received an infusion of CTL019
Arm/Group Title Tisagenlecleucel - FAS Pts Who Achieved CR/CRi & Then Relapsed
Hide Arm/Group Description:
Pediatric participants with r/r B-cell who were infused with tisagenlecleucel and then relapsed
Overall Number of Participants Analyzed 21
Measure Type: Number
Unit of Measure: Percentage of participants
BM/blood relapse 72.2
Extramedullary only 27.8
Unknown 16.7
34.Secondary Outcome
Title Time to B-cell Recovery in Participants Who Achieved CR or CRi by IRC
Hide Description Time to B cell recovery was defined as the time from onset of remission to the earliest time when the percentage of CD19+ total B cell among viable WBC is ≥ 1% or among lymphocyte is at least 3%.
Time Frame during the whole study, up to 60 months
Hide Outcome Measure Data
Hide Analysis Population Description
FAS patients who achieved CR or CRi. FAS: All subjects who received an infusion of CTL019
Arm/Group Title Tisagenlecleucel (CTL019) - All Participants
Hide Arm/Group Description:
Pediatric participants with r/r B-cell who were infused with tisagenlecleucel
Overall Number of Participants Analyzed 54
Median (95% Confidence Interval)
Unit of Measure: Months
35.5 [1] 
(7.6 to NA)
[1]
N/A = not estimable because there were not enough participants who had events to estimate the upper limit of the median
35.Secondary Outcome
Title Percentage of CD19+ B Cell Levels in Peripheral Blood by Day 28 Disease Response by IRC Assessment
Hide Description The levels (%) of CD19+ total B cells amongst viable white blood cells (WBC) in peripheral blood
Time Frame Enrollment/Pre-Chemotherapy; Pre-infusion; Baseline; Day 7; Day 14; Day 21; Day 28; Month 3; Month 6; Month 9; Month 12; Month 24; Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set: All subjects who received an infusion of tisagenlecleucel
Arm/Group Title CR/CRi No Response Unknown
Hide Arm/Group Description:
Participants had Complete remission (CR)/Complete remission with incomplete blood count recovery (CRi)
No response was defined as failure to attain the criteria needed for any response categories or relapse
unknown was assigned in case the baseline assessment or the response assessment was not done, incomplete, indeterminate or not performed within the respective time frame.
Overall Number of Participants Analyzed 52 6 6
Mean (Standard Deviation)
Unit of Measure: Percentage of CD19+ B cell levels
Enrollment/Pre-Chemotherapy Number Analyzed 50 participants 6 participants 6 participants
26.8  (28.733) 52.29  (36.758) 32.66  (28.102)
Pre-infusion Number Analyzed 1 participants 0 participants 1 participants
0.02 [1]   (NA) 46.80 [1]   (NA)
Baseline Number Analyzed 50 participants 6 participants 6 participants
25.11  (28.584) 52.29  (36.758) 29.50  (24.466)
Day 7 Number Analyzed 45 participants 6 participants 6 participants
1.06  (3.735) 34.40  (46.922) 23.18  (38.772)
Day 14 Number Analyzed 50 participants 6 participants 5 participants
0.73  (5.096) 33.76  (45.359) 3.43  (7.520)
Day 21 Number Analyzed 46 participants 6 participants 5 participants
0.01  (0.017) 19.67  (32.553) 16.13  (35.929)
Day 28 Number Analyzed 48 participants 6 participants 3 participants
0.02  (0.069) 34.97  (36.648) 0.02  (0.012)
Month 3 Number Analyzed 44 participants 1 participants 2 participants
0.79  (1.971) 0.57 [1]   (NA) 11.26  (15.917)
Month 6 Number Analyzed 37 participants 1 participants 1 participants
1.86  (7.958) 9.70 [1]   (NA) 0.01 [1]   (NA)
Month 9 Number Analyzed 27 participants 0 participants 0 participants
0.63  (2.180)
Month 12 Number Analyzed 27 participants 0 participants 0 participants
0.85  (2.420)
Month 24 Number Analyzed 14 participants 0 participants 0 participants
1.74  (3.446)
Month 36 Number Analyzed 6 participants 0 participants 0 participants
1.10  (2.106)
[1]
N/A = Too few participants to calculate geometric SD
36.Secondary Outcome
Title Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: C Reactive Protein (CRP)
Hide Description C-Reactive Protein at Pre-infusion, baseline, and change from baseline for Days 7, 14, 21, 28, Month 3
Time Frame Pre-infusion, Baseline, Day 7, Day 14, Day 21, Day 28, Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set: All subjects who received an infusion of tisagenlecleucel
Arm/Group Title NO CRS Grade 1/2 Grade 3 Grade 4 All Participants
Hide Arm/Group Description:
No cytokine release syndrome
Grade 1 and 2 of cytokine release syndrome post tisagenlecleucel infusion
Grade 3 of cytokine release syndrome post tisagenlecleucel infusion
Grade 4 of cytokine release syndrome post tisagenlecleucel infusion
All participants with & without CRS
Overall Number of Participants Analyzed 14 31 8 11 64
Median (Full Range)
Unit of Measure: mg/L
Pre-infusion Number Analyzed 14 participants 29 participants 8 participants 9 participants 60 participants
9.21
(2.9 to 34.0)
8.27
(2.0 to 1530.0)
7.45
(0.6 to 50.0)
9.00
(2.0 to 153.0)
9.00
(0.6 to 1530.0)
Baseline (BL) Number Analyzed 14 participants 30 participants 8 participants 9 participants 61 participants
9.21
(2.9 to 34.0)
9.04
(2.0 to 1530.0)
7.45
(0.6 to 50.0)
9.00
(2.0 to 153.0)
9.00
(0.6 to 1530.0)
Change from BL Day7 Number Analyzed 14 participants 30 participants 8 participants 9 participants 61 participants
0.00
(-15.0 to 25.0)
15.00
(-460.0 to 215.0)
79.55
(-2.0 to 380.0)
108.00
(-125.0 to 255.0)
9.10
(-460.0 to 380.0)
Change from BL Day 14 Number Analyzed 14 participants 30 participants 8 participants 9 participants 61 participants
0.00
(-20.0 to 24.0)
0.00
(-1031.0 to 215.0)
10.50
(-42.0 to 199.0)
15.70
(-148.0 to 100.0)
0.00
(-1031.0 to 215.0)
Change from BL Day 21 Number Analyzed 14 participants 28 participants 8 participants 7 participants 57 participants
0.00
(-14.0 to 29.5)
-0.80
(-1460.0 to 677.0)
2.00
(-42.0 to 37.0)
-3.00
(-57.0 to 73.0)
0.00
(-1460.0 to 677.0)
Change from BL Day 28 Number Analyzed 14 participants 27 participants 8 participants 9 participants 59 participants
0.00
(-15.0 to 47.0)
-0.70
(-1487.0 to 47.0)
1.50
(-45.0 to 55.0)
-3.00
(-151.0 to 27.0)
0.00
(-1487.0 to 55.0)
Change from BL Month 3 Number Analyzed 11 participants 23 participants 5 participants 7 participants 46 participants
0.00
(-12.1 to 101.0)
-1.00
(-1501.0 to 7.1)
0.00
(-3.0 to 120.5)
-1.00
(-149.0 to 13.0)
-0.65
(-1501.0 to 120.5)
37.Secondary Outcome
Title Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Ferritin
Hide Description Ferritin at Pre-infusion, baseline, and change from baseline for Days 7, 14, 21, 28, Month 3
Time Frame Pre-infusion, Baseline, Day 7, Day 14, Day 21, Day 28, Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set: All subjects who received an infusion of tisagenlecleucel
Arm/Group Title NO CRS Grade 1/2 Grade 3 Grade 4 All Participants
Hide Arm/Group Description:
No cytokine release syndrome
Grade 1 and 2 of cytokine release syndrome post tisagenlecleucel infusion
Grade 3 of cytokine release syndrome post tisagenlecleucel infusion
Grade 4 of cytokine release syndrome post tisagenlecleucel infusion
All participants with & without CRS
Overall Number of Participants Analyzed 14 31 8 11 64
Median (Full Range)
Unit of Measure: ug/L
Pre-infusion Number Analyzed 14 participants 26 participants 8 participants 9 participants 54 participants
1865.20
(459.0 to 5015.0)
2202.22
(230.0 to 18061.0)
1906.95
(357.0 to 4200.0)
2078.40
(487.0 to 13553.9)
1983.90
(230.0 to 18061.0)
Baseline (BL) Number Analyzed 14 participants 30 participants 8 participants 9 participants 61 participants
1865.20
(459.0 to 5015.0)
2202.22
(230.0 to 18061.0)
1906.95
(357.0 to 4200.0)
2078.40
(487.0 to 13553.9)
1983.90
(230.0 to 18061.0)
Change from BL Day7 Number Analyzed 14 participants 29 participants 8 participants 9 participants 60 participants
-146.50
(-721.4 to 710.0)
377.80
(-1468.0 to 522220.0)
22735.10
(-330.0 to 182380.0)
23788.71
(-161.0 to 269529.0)
358.90
(-1468.0 to 269529.0)
Change from BL Day 14 Number Analyzed 14 participants 30 participants 8 participants 9 participants 61 participants
-321.30
(-2035.1 to 520.0)
861.50
(-3483.3 to 59435.9)
10728.40
(1262.0 to 104170.0)
18580.01
(707.0 to 110421.6)
973.00
(-3483.3 to 110421.6)
Change from BL Day 21 Number Analyzed 14 participants 29 participants 8 participants 8 participants 59 participants
58.00
(-2302.0 to 524.0)
331.00
(-3571.6 to 43336.0)
3299.85
(-600.0 to 121100.0)
3199.00
(-17.0 to 12957.4)
490.00
(-3571.6 to 121100.0)
Change from BL Day 28 Number Analyzed 14 participants 27 participants 8 participants 9 participants 58 participants
121.10
(-2952.0 to 1510.0)
283.00
(-6443. to 9879.0)
1104.00
(-890.0 to 331000.0)
1211.00
(-606.0 to 12957.4)
280.50
(-6443.7 to 33100.0)
Change from BL Month 3 Number Analyzed 11 participants 23 participants 5 participants 7 participants 46 participants
-124.90
(-2418.0 to 1985.5)
-358.00
(-5415.0 to 7050.0)
-487.60
(-1500.0 to 8140.0)
-377.00
(-1808.2 to 2641.6)
-330.00
(-5415.0 to 8140.0)
38.Secondary Outcome
Title Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: INF-gamma
Hide Description INF-gamma at Pre-infusion, baseline, and change from baseline for Days 7, 14, 21, 28, Month 3
Time Frame Pre-infusion, Baseline, Day 7, Day 14, Day 21, Day 28, Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set: All subjects who received an infusion of tisagenlecleucel
Arm/Group Title NO CRS Grade 1/2 Grade 3 Grade 4 All Participants
Hide Arm/Group Description:
No cytokine release syndrome
Grade 1 and 2 of cytokine release syndrome post tisagenlecleucel infusion
Grade 3 of cytokine release syndrome post tisagenlecleucel infusion
Grade 4 of cytokine release syndrome post tisagenlecleucel infusion
All participants with & without CRS
Overall Number of Participants Analyzed 14 31 8 11 64
Median (Full Range)
Unit of Measure: pg/mL
Pre-infusion Number Analyzed 14 participants 30 participants 8 participants 9 participants 61 participants
29.63
(1.0 to 283.0)
23.39
(1.0 to 242.8)
15.73
(6.4 to 31.5)
5.79
(2.5 to 34.1)
20.22
(1.0 to 283.0)
Baseline (BL) Number Analyzed 14 participants 31 participants 8 participants 9 participants 63 participants
29.63
(1.0 to 283.0)
22.51
(1.0 to 242.8)
15.73
(6.4 to 31.5)
4.77
(1.0 to 34.1)
15.75
(1.0 to 283.0)
Change from BL Day7 Number Analyzed 14 participants 31 participants 8 participants 10 participants 63 participants
0.47
(-167.9 to 140.6)
52.59
(-201.2 to 39452.4)
3023.82
(-14.7 to 162376.0)
1347.48
(60.2 to 89599.0)
72.09
(-201.2 to 162376.0)
Change from BL Day 14 Number Analyzed 13 participants 30 participants 8 participants 9 participants 60 participants
-5.10
(-278.3 to 39.2)
-4.44
(-194.8 to 131.1)
58.65
(-14.3 to 1328.7)
102.04
(-2.2 to 8925.9)
1.32
(-278.3 to 8925.9)
Change from BL Day 21 Number Analyzed 13 participants 29 participants 8 participants 8 participants 58 participants
-4.97
(-264.0 to 58.5)
1.06
(-219.7 to 1384.6)
0.53
(-22.8 to 1048.7)
5.23
(-4.0 to 167.1)
-0.89
(-264.0 to 1384.6)
Change from BL Day 28 Number Analyzed 14 participants 28 participants 8 participants 9 participants 59 participants
-6.93
(-269.9 to 60.4)
0.20
(-223.6 to 738.8)
-1.19
(-26.1 to 187.7)
0.36
(-4.7 to 138.4)
-0.62
(-269.9 to 738.8)
Change from BL Month 3 Number Analyzed 11 participants 22 participants 6 participants 6 participants 45 participants
-6.08
(-278.6 to 167.5)
-14.58
(-173.9 to 7.6)
21.25
(-7.7 to 37.2)
-0.67
(-4.4 to 23.1)
-5.71
(-278.6 to 167.5)
39.Secondary Outcome
Title Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-6 (IL-6)
Hide Description IL-6 at Pre-infusion, baseline, and change from baseline for Days 7, 14, 21, 28, Month 3
Time Frame Pre-infusion, Baseline, Day 7, Day 14, Day 21, Day 28, Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set: All subjects who received an infusion of tisagenlecleucel
Arm/Group Title NO CRS Grade 1/2 Grade 3 Grade 4 All Participants
Hide Arm/Group Description:
No cytokine release syndrome
Grade 1 and 2 of cytokine release syndrome post tisagenlecleucel infusion
Grade 3 of cytokine release syndrome post tisagenlecleucel infusion
Grade 4 of cytokine release syndrome post tisagenlecleucel infusion
All participants with & without CRS
Overall Number of Participants Analyzed 14 31 8 11 64
Median (Full Range)
Unit of Measure: pg/mL
Pre-infusion Number Analyzed 14 participants 30 participants 8 participants 9 participants 61 participants
2.42
(0.4 to 12.0)
2.89
(0.2 to 19.6)
1.00
(0.8 to 9.4)
2.27
(0.4 to 6.2)
2.27
(0.2 to 19.6)
Baseline (BL) Number Analyzed 14 participants 31 participants 8 participants 10 participants 63 participants
2.42
(0.4 to 12.0)
2.83
(0.2 to 19.6)
1.00
(0.8 to 9.4)
1.84
(0.2 to 6.2)
1.99
(0.2 to 19.6)
Change from BL Day7 Number Analyzed 14 participants 31 participants 8 participants 10 participants 63 participants
-0.23
(-9.6 to 4.3)
2.64
(-13.1 to 61.3)
52.75
(-0.6 to 7201.6)
141.68
(1.3 to 12615.8)
2.64
(-13.1 to 12615.8)
Change from BL Day 14 Number Analyzed 13 participants 30 participants 8 participants 9 participants 60 participants
-0.36
(-2.3 to 4.1)
-0.67
(-13.4 to 21.5)
8.88
(-0.6 to 30.4)
165.16
(-0.2 to 5734.8)
-0.11
(-13.4 to 5734.8)
Change from BL Day 21 Number Analyzed 13 participants 29 participants 8 participants 8 participants 58 participants
-0.97
(-5.3 to 5.3)
-0.46
(-15.4 to 103.4)
1.65
(-0.6 to 265.2)
50.75
(-0.2 to 5734.8)
-0.09
(-15.4 to 5734.8)
Change from BL Day 28 Number Analyzed 14 participants 28 participants 8 participants 9 participants 59 participants
-0.98
(-7.8 to 1.9)
-0.28
(-17.5 to 33.0)
0.91
(-0.6 to 138.6)
38.13
(-0.0 to 2148.4)
-0.03
(-17.5 to 2148.4)
Change from BL Month 3 Number Analyzed 11 participants 22 participants 6 participants 6 participants 45 participants
0.34
(-10.8 to 22.7)
-0.59
(-8.9 to 1.2)
0.56
(-0.6 to 30.3)
0.40
(-0.9 to 3.2)
-0.19
(-10.8 to 30.3)
40.Secondary Outcome
Title Key Inflammatory Markers and Cytokine Parameters in Blood Within 1 Month by Maximum Cytokine Release Syndrome (CRS) Grade: Interleukin-2 (IL-2)
Hide Description IL-2 at Pre-infusion, baseline, and change from baseline for Days 7, 14, 21, 28, Month 3
Time Frame Pre-infusion, Baseline, Day 7, Day 14, Day 21, Day 28, Month 3
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set: All subjects who received an infusion of tisagenlecleucel
Arm/Group Title NO CRS Grade 1/2 Grade 3 Grade 4 All Participants
Hide Arm/Group Description:
No cytokine release syndrome
Grade 1 and 2 of cytokine release syndrome post tisagenlecleucel infusion
Grade 3 of cytokine release syndrome post tisagenlecleucel infusion
Grade 4 of cytokine release syndrome post tisagenlecleucel infusion
All participants with & without CRS
Overall Number of Participants Analyzed 14 31 8 11 64
Median (Full Range)
Unit of Measure: pg/mL
Pre-infusion Number Analyzed 14 participants 30 participants 8 participants 9 participants 61 participants
2.3
(2.3 to 2.3)
2.3
(2.3 to 2.3)
2.3
(2.3 to 2.3)
2.3
(2.3 to 2.3)
2.3
(2.3 to 2.3)
Baseline (BL) Number Analyzed 14 participants 31 participants 8 participants 10 participants 63 participants
2.3
(2.3 to 2.3)
2.3
(2.3 to 2.3)
2.3
(2.3 to 2.3)
2.3
(2.3 to 2.3)
2.3
(2.3 to 2.3)
Change from BL Day7 Number Analyzed 14 participants 31 participants 8 participants 10 participants 63 participants
3.33
(0.0 to 6.7)
3.15
(0.0 to 7.0)
13.14
(5.0 to 63.7)
7.48
(2.9 to 12.1)
5.16
(0.0 to 63.7)
Change from BL Day 14 Number Analyzed 13 participants 30 participants 8 participants 9 participants 60 participants
NA [1] 
(NA to NA)
0.00
(0.00 to 0.00)
NA [1] 
(NA to NA)
4.56
(4.56 to 4.6)
0.00
(0.0 to 4.6)
Change from BL Day 21 Number Analyzed 13 participants 29 participants 8 participants 8 participants 58 participants
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Change from BL Day 28 Number Analyzed 14 participants 28 participants 8 participants 9 participants 59 participants
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Change from BL Month 3 Number Analyzed 11 participants 22 participants 6 participants 6 participants 45 participants
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
N/A = below limit of detection
Time Frame Adverse Event (AE) timeframe: Adverse events were collected during the post-infusion period (starting at the day of first infusion until the end of the study), up to maximum duration of 60 months for each patient.
Adverse Event Reporting Description AE description: Any sign or symptom that occurs during the post-infusion period (starting at the day of first infusion of CTL019 until the end of the study).
 
Arm/Group Title Tisagenlecleucel (CTL019) - All Participants
Hide Arm/Group Description Pediatric participants with r/r B-cell who were infused with tisagenlecleucel
All-Cause Mortality
Tisagenlecleucel (CTL019) - All Participants
Affected / at Risk (%)
Total   30/64 (46.88%) 
Hide Serious Adverse Events
Tisagenlecleucel (CTL019) - All Participants
Affected / at Risk (%)
Total   52/64 (81.25%) 
Blood and lymphatic system disorders   
Disseminated intravascular coagulation  1  2/64 (3.13%) 
Eosinophilia  1  1/64 (1.56%) 
Febrile neutropenia  1  23/64 (35.94%) 
Neutropenia  1  3/64 (4.69%) 
Cardiac disorders   
Atrioventricular block second degree  1  1/64 (1.56%) 
Ventricular tachycardia  1  1/64 (1.56%) 
Eye disorders   
Papilloedema  1  1/64 (1.56%) 
Vision blurred  1  1/64 (1.56%) 
Gastrointestinal disorders   
Diarrhoea  1  2/64 (3.13%) 
Enterocolitis  1  1/64 (1.56%) 
Intestinal obstruction  1  1/64 (1.56%) 
Pancreatitis  1  1/64 (1.56%) 
Stomatitis  1  1/64 (1.56%) 
Vomiting  1  1/64 (1.56%) 
General disorders   
Malaise  1  1/64 (1.56%) 
Physical deconditioning  1  1/64 (1.56%) 
Pyrexia  1  7/64 (10.94%) 
Immune system disorders   
Cytokine release syndrome  1  41/64 (64.06%) 
Graft versus host disease in gastrointestinal tract  1  1/64 (1.56%) 
Infections and infestations   
Bacterial sepsis  1  1/64 (1.56%) 
Campylobacter infection  1  1/64 (1.56%) 
Catheter site infection  1  1/64 (1.56%) 
Cellulitis of male external genital organ  1  1/64 (1.56%) 
Cholecystitis infective  1  1/64 (1.56%) 
Clostridium difficile colitis  1  2/64 (3.13%) 
Clostridium difficile infection  1  3/64 (4.69%) 
Corona virus infection  1  1/64 (1.56%) 
Enterovirus infection  1  1/64 (1.56%) 
Gastroenteritis  1  1/64 (1.56%) 
Gastroenteritis norovirus  1  1/64 (1.56%) 
Herpes zoster  1  1/64 (1.56%) 
Parainfluenzae virus infection  1  1/64 (1.56%) 
Pneumonia  1  2/64 (3.13%) 
Respiratory syncytial virus infection  1  1/64 (1.56%) 
Respiratory tract infection  1  1/64 (1.56%) 
Respiratory tract infection viral  1  1/64 (1.56%) 
Rhinovirus infection  1  1/64 (1.56%) 
Rotavirus infection  1  1/64 (1.56%) 
Sepsis  1  1/64 (1.56%) 
Septic embolus  1  1/64 (1.56%) 
Staphylococcal infection  1  1/64 (1.56%) 
Upper respiratory tract infection  1  1/64 (1.56%) 
Urinary tract infection  1  2/64 (3.13%) 
Vascular device infection  1  1/64 (1.56%) 
Viral upper respiratory tract infection  1  1/64 (1.56%) 
Vulvovaginal candidiasis  1  1/64 (1.56%) 
Injury, poisoning and procedural complications   
Procedural pain  1  1/64 (1.56%) 
Transfusion related complication  1  1/64 (1.56%) 
Investigations   
Alanine aminotransferase increased  1  1/64 (1.56%) 
White blood cell count decreased  1  1/64 (1.56%) 
Metabolism and nutrition disorders   
Acidosis  1  1/64 (1.56%) 
Decreased appetite  1  1/64 (1.56%) 
Dehydration  1  1/64 (1.56%) 
Tumour lysis syndrome  1  2/64 (3.13%) 
Musculoskeletal and connective tissue disorders   
Flank pain  1  1/64 (1.56%) 
Osteonecrosis  1  1/64 (1.56%) 
Pain in extremity  1  1/64 (1.56%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Glioblastoma multiforme  1  1/64 (1.56%) 
Myelodysplastic syndrome  1  1/64 (1.56%) 
Nervous system disorders   
Embolic stroke  1  1/64 (1.56%) 
Encephalopathy  1  4/64 (6.25%) 
Headache  1  1/64 (1.56%) 
Idiopathic intracranial hypertension  1  1/64 (1.56%) 
Seizure  1  4/64 (6.25%) 
Psychiatric disorders   
Delirium  1  1/64 (1.56%) 
Renal and urinary disorders   
Acute kidney injury  1  4/64 (6.25%) 
Renal failure  1  1/64 (1.56%) 
Reproductive system and breast disorders   
Vaginal haemorrhage  1  1/64 (1.56%) 
Respiratory, thoracic and mediastinal disorders   
Acute respiratory failure  1  1/64 (1.56%) 
Hypoxia  1  4/64 (6.25%) 
Pleural effusion  1  2/64 (3.13%) 
Pulmonary oedema  1  2/64 (3.13%) 
Respiratory failure  1  3/64 (4.69%) 
Skin and subcutaneous tissue disorders   
Ecchymosis  1  1/64 (1.56%) 
Vascular disorders   
Embolism  1  1/64 (1.56%) 
Hypotension  1  7/64 (10.94%) 
1
Term from vocabulary, MedDRA (22.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Tisagenlecleucel (CTL019) - All Participants
Affected / at Risk (%)
Total   64/64 (100.00%) 
Blood and lymphatic system disorders   
Anaemia  1  27/64 (42.19%) 
Lymphopenia  1  4/64 (6.25%) 
Neutropenia  1  8/64 (12.50%) 
Thrombocytopenia  1  10/64 (15.63%) 
Cardiac disorders   
Sinus tachycardia  1  6/64 (9.38%) 
Tachycardia  1  15/64 (23.44%) 
Eye disorders   
Periorbital oedema  1  4/64 (6.25%) 
Gastrointestinal disorders   
Abdominal pain  1  11/64 (17.19%) 
Constipation  1  7/64 (10.94%) 
Diarrhoea  1  22/64 (34.38%) 
Nausea  1  25/64 (39.06%) 
Vomiting  1  27/64 (42.19%) 
General disorders   
Catheter site pain  1  4/64 (6.25%) 
Chills  1  10/64 (15.63%) 
Fatigue  1  15/64 (23.44%) 
Pain  1  4/64 (6.25%) 
Pyrexia  1  21/64 (32.81%) 
Immune system disorders   
Cytokine release syndrome  1  19/64 (29.69%) 
Hypogammaglobulinaemia  1  33/64 (51.56%) 
Infections and infestations   
Gastroenteritis  1  4/64 (6.25%) 
Influenza  1  4/64 (6.25%) 
Otitis media  1  4/64 (6.25%) 
Rhinovirus infection  1  4/64 (6.25%) 
Sinusitis  1  4/64 (6.25%) 
Upper respiratory tract infection  1  8/64 (12.50%) 
Urinary tract infection  1  4/64 (6.25%) 
Injury, poisoning and procedural complications   
Infusion related reaction  1  4/64 (6.25%) 
Procedural pain  1  5/64 (7.81%) 
Investigations   
Activated partial thromboplastin time prolonged  1  5/64 (7.81%) 
Alanine aminotransferase increased  1  21/64 (32.81%) 
Aspartate aminotransferase increased  1  20/64 (31.25%) 
Blood bilirubin increased  1  8/64 (12.50%) 
Blood creatinine increased  1  9/64 (14.06%) 
Blood fibrinogen decreased  1  4/64 (6.25%) 
Blood immunoglobulin M decreased  1  4/64 (6.25%) 
International normalised ratio increased  1  9/64 (14.06%) 
Lymphocyte count decreased  1  16/64 (25.00%) 
Neutrophil count decreased  1  28/64 (43.75%) 
Platelet count decreased  1  20/64 (31.25%) 
Prothrombin time prolonged  1  9/64 (14.06%) 
Weight decreased  1  4/64 (6.25%) 
White blood cell count decreased  1  35/64 (54.69%) 
Metabolism and nutrition disorders   
Decreased appetite  1  21/64 (32.81%) 
Hypernatraemia  1  4/64 (6.25%) 
Hyperphosphataemia  1  8/64 (12.50%) 
Hypoalbuminaemia  1  5/64 (7.81%) 
Hypokalaemia  1  19/64 (29.69%) 
Hypophosphataemia  1  10/64 (15.63%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  5/64 (7.81%) 
Myalgia  1  5/64 (7.81%) 
Pain in extremity  1  10/64 (15.63%) 
Nervous system disorders   
Dizziness  1  6/64 (9.38%) 
Headache  1  24/64 (37.50%) 
Psychiatric disorders   
Anxiety  1  7/64 (10.94%) 
Confusional state  1  6/64 (9.38%) 
Renal and urinary disorders   
Acute kidney injury  1  5/64 (7.81%) 
Haematuria  1  5/64 (7.81%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  14/64 (21.88%) 
Epistaxis  1  10/64 (15.63%) 
Hypoxia  1  6/64 (9.38%) 
Nasal congestion  1  5/64 (7.81%) 
Oropharyngeal pain  1  6/64 (9.38%) 
Pleural effusion  1  6/64 (9.38%) 
Pulmonary oedema  1  5/64 (7.81%) 
Rhinitis allergic  1  4/64 (6.25%) 
Rhinorrhoea  1  6/64 (9.38%) 
Tachypnoea  1  5/64 (7.81%) 
Skin and subcutaneous tissue disorders   
Dry skin  1  5/64 (7.81%) 
Erythema  1  5/64 (7.81%) 
Hyperhidrosis  1  4/64 (6.25%) 
Petechiae  1  4/64 (6.25%) 
Pruritus  1  4/64 (6.25%) 
Rash  1  8/64 (12.50%) 
Rash maculo-papular  1  5/64 (7.81%) 
Vascular disorders   
Hypertension  1  12/64 (18.75%) 
Hypotension  1  9/64 (14.06%) 
1
Term from vocabulary, MedDRA (22.0)
Indicates events were collected by systematic assessment
Safety data reported is based on all the 64 infused patients with data cutoff of 24May2019.
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 terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02228096    
Other Study ID Numbers: CCTL019B2205J
2015-003736-13 ( EudraCT Number )
First Submitted: August 26, 2014
First Posted: August 28, 2014
Results First Submitted: November 22, 2019
Results First Posted: November 23, 2020
Last Update Posted: November 23, 2020