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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-001991-31 | EudraCT Number |
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This is a single arm, open-label, multi-center, phase III B study to determine the safety and efficacy of CTL019 in pediatric/young adult patients with r/r B-cell Acute Lymphoblastic Leukemia (ALL).
This was a single-arm, multi-centeric Phase IIIb study provided pediatric/young adult patients with r/r B-cell ALL the opportunity to be treated with CTL019. The main purpose of this study was to assess the safety of CTL019 for up to 12 months after the CTL019 infusion. The study had the following sequential phases for all patients: Screening including leukapheresis, Pre-Treatment (Cell Product Preparation and Lymphodepleting Chemotherapy), Treatment and Follow-up, and Long-Term Follow-Up (LTFU). The end of study (EOS) was defined as the last patient's last visit, which was the last patient's Month 12 evaluation, or the time of premature withdrawal. All patients were followed in this study for up to 12 months after the CTL019 infusion.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CTL019 | Experimental | CTL019 transduced T cells were given as a single dose of 0.2 to 5.0 × 10^6 autologous CTL019 transduced viable T cells per kg body weight (for patients ≤ 50 kg) and 0.1 to 2.5 × 10^8 CTL019 transduced viable T cells (for patients > 50 kg) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CTL019 | Biological | CTL019 transduced T cells were given as a single dose of 0.2 to 5.0 × 10^6 autologous CTL019 transduced viable T cells per kg body weight (for patients ≤ 50 kg) and 0.1 to 2.5 × 10^8 CTL019 transduced viable T cells (for patients > 50 kg) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment emergent adverse events were collected from CTL019 infusion until end of study, up to 12 months | From CTL019 infusion until end of study, up to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Remission Rate (ORR) | ORR is defined as the proportion of participants with a best overall disease response of Complete remission (CR) or CR with incomplete blood count recovery (CRi), where the best overall disease response is defined as the best disease response recorded from CTL019 infusion until Month 6. | From CTL019 infusion until Month 6 |
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Inclusion Criteria:
Relapsed or refractory B-cell ALL in pediatric or young adult patients:
For relapsed patients, CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry within 3 months of program entry.For relapsed or refractory patients previously treated with blinatumomab, CD19 tumor expression must be demonstrated (via flow cytometry) at Screening.
Adequate organ function defined as:
Life expectancy > 12 weeks.
Age less than 26 at the time of screening.
Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status ≥ 50 at screening.
Patients previously treated with blinatumomab who have detectable leukemia and documented CD19+ expression (via flow cytometry) and confirmed absence of CD19- leukemic blasts at Screening may be included. In this case, at least 1 week washout period must be applied from last dose of blinatumomab to start of leukapheresis. Patients previously treated with blinatumomab with no detectable MRD (i.e. MRD negative demonstrated by leukemic blasts < 0.01%) will be excluded.
Must have a leukapheresis product of non-mobilized cells received and accepted by the manufacturing site.
Patients with active CNS leukemia involvement defined as CNS-3 by CSF findings only are eligible but will have their CTL019 infusion delayed until CNS disease is reduced to CNS-1 or CNS-2 by CSF findings. Patients with other forms of active CNS-3 leukemic involvement such as CNS parenchymal or ocular disease, cranial nerve involvement or significant leptomeningeal disease are not eligible. However, such patients with other forms of CNS-3 leukemic involvement (non-CSF involvement) are eligible if there is documented evidence of disease stabilization for at least 3 months prior to CTL019 infusion. Patients must have no acute/ongoing neurologic toxicity > Grade 1 with the exception of a history of controlled seizures or fixed neurologic deficits that have been stable/improving over the past 3 months.
Exclusion criteria Isolated extra-medullary disease relapse. Concomitant genetic syndromes associated with bone marrow failure states: Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Patients with Down Syndrome will not be excluded.
Patients with Burkitt's lymphoma/leukemia (i.e. patients with mature B-cell ALL, leukemia with B-cell surface immunoglobulin (sIg) positive and kappa or lambda restricted positivity ALL, with FAB L3 morphology and /or a MYC translocation).
Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease.
Prior treatment with any gene therapy product. Prior treatment with any anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy, except for patients pre-treated with blinatumomab Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening), or any uncontrolled infection at screening Human immunodeficiency virus (HIV) positive test within 8 weeks of screening. Presence of grade 2 to 4 acute or extensive chronic GVHD. Uncontrolled acute life threatening bacterial, viral or fungal infection at Screening Investigational medicinal product within the last 30 days prior to screening. Pregnant or nursing women.Women of child-bearing potential and all male participants, unless they are using highly effective methods of contraception for a period of 1 year after the CTL019 infusion.
The following medications are excluded:
Steroids: Therapeutic systemic doses of steroids must be stopped > 72 hours prior to CTL019 infusion.
Allogeneic cellular therapy: Any donor lymphocyte infusions must be completed > 6 weeks prior to CTL019 infusion.
GVHD therapies: Any systemic drug used for GVHD must be stopped > 4 weeks prior to CTL019 infusion to confirm that GVHD recurrence is not observed.
Chemotherapy:
CNS disease prophylaxis: CNS prophylaxis treatment must be stopped > 1 week prior to CTL019 infusion (e.g. intrathecal methotrexate).
Radiotherapy
Anti T-cell antibodies: Administration of any T cell lytic or toxic antibody (e.g. alemtuzumab) within 8 weeks prior to CTL019 is prohibited Other protocol-defined inclusion/exclusion may apply
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Vienna | A 1090 | Austria | |||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35422096 | Derived | Laetsch TW, Maude SL, Balduzzi A, Rives S, Bittencourt H, Boyer MW, Buechner J, De Moerloose B, Qayed M, Phillips CL, Pulsipher MA, Hiramatsu H, Tiwari R, Grupp SA. Tisagenlecleucel in pediatric and young adult patients with Down syndrome-associated relapsed/refractory acute lymphoblastic leukemia. Leukemia. 2022 Jun;36(6):1508-1515. doi: 10.1038/s41375-022-01550-z. Epub 2022 Apr 14. |
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Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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This was a single arm study.
Participants were enrolled in 11 study centers across 9 countries (Austria, Belgium, Canada, Germany, Spain, France, Italy, Japan, Norway).
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| ID | Title | Description |
|---|---|---|
| FG000 | CTL019 | CTL019 transduced T cells were given as a single dose of 0.2 to 5.0 × 10^6 autologous CTL019 transduced viable T cells per kg body weight (for patients ≤ 50 kg) and 0.1 to 2.5 × 10^8 CTL019 transduced viable T cells (for patients > 50 kg) |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Full Analysis Set (FAS) comprised of all the participants who received an infusion of CTL019
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| ID | Title | Description |
|---|---|---|
| BG000 | CTL019 | CTL019 transduced T cells were given as a single dose of 0.2 to 5.0 × 10^6 autologous CTL019 transduced viable T cells per kg body weight (for patients ≤ 50 kg) and 0.1 to 2.5 × 10^8 CTL019 transduced viable T cells (for patients > 50 kg) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment emergent adverse events were collected from CTL019 infusion until end of study, up to 12 months | The Safety Set (SAF) comprised of all the participants who received an infusion of CTL019 | Posted | Count of Participants | Participants | From CTL019 infusion until end of study, up to 12 months |
|
Treatment-emergent adverse events were collected from CTL019 infusion, until approximately 12 months post infusion. For all-cause mortality, the data are presented from CTL019 infusion up to 24.4 months post infusion.
Any signs or symptoms that occurred from CTL019 infusion until end of study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Subjects - CTL019 | CTL019 transduced T cells were given as a single dose of 0.2 to 5.0 × 10^6 autologous CTL019 transduced viable T cells per kg body weight (for patients ≤ 50 kg) and 0.1 to 2.5 × 10^8 CTL019 transduced viable T cells (for patients > 50 kg) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | Novartis.email@novartis.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 6, 2019 | Apr 12, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 4, 2020 | Apr 12, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C000626284 | tisagenlecleucel |
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| Number of Participants Who Achieved CR or CRi at Month 6 Without Stem Cell Transplantation (SCT) | Proportion of participants who achieved CR or CRi at Month 6 without stem cell transplantation between CTL019 infusion and Month 6 response assessment | Month 6 |
| Number of Participants Who Achieved CR or CRi and Then Proceeded to Stem Cell Transplantation (SCT) While in Remission Before Month 6 Assessment | Proportion of participants who achieved CR or CRi and then proceeded to stem cell transplantation while in remission prior to Month 6 response assessment. | From CTL019 infusion until Month 6 |
| Duration of Response (DOR) | DOR is the duration of remission from the date when the response criteria of CR or CRi was first met post CTL019 infusion to the date of relapse or death due to acute lymphoblastic leukemia (ALL), whichever occured first. | Actual reported Time Frame: up to 14.4 months post CTL019 infusion (planned follow-up period per protocol was only 12 months post CTL019 infusion) |
| Relapse-free Survival (RFS) | RFS is measured by the time from achievement of CR or CRi whichever occured first post CTL019 infusion, to relapse or death due to any cause during CR or CRi. | Actual reported Time Frame: up to 14.4 months post CTL019 infusion (planned follow-up period per protocol was only 12 months post CTL019 infusion) |
| Event-free Survival (EFS) | EFS is the time from date of CTL019 infusion to the earliest of death, relapse or treatment failure. | Actual reported Time Frame: up to 15.1 months post CTL019 infusion (planned follow-up period per protocol was only 12 months post CTL019 infusion) |
| Overall Survival (OS) | OS is the time from date of CTL019 infusion to the date of death due to any reason | Actual reported Time Frame: up to 24.4 months post CTL019 infusion (planned follow-up period per protocol was only 12 months post CTL019 infusion) |
| Number of Participants Who Attained CR or CRi at Day 28 | Proportion of participants who attained CR or CRi at Day 28 post CTL019 infusion. | Day 28 |
| Number of Participants Who Attained CR or CRi at Day 28 by Baseline Bone Marrow Tumor Burden | Proportion of participants who attained CR or CRi at Day 28 post CTL019 infusion by baseline bone marrow tumor burden. | Day 28 |
| Bone Marrow Minimum Residual Disease (MRD) Status by Flow Cytometry on Day 28 Post CTL019 Infusion | MRD in ALL refers to the presence of leukemic cells below the threshold of detection using conventional morphologic methods. The most frequently used methods for MRD assessment include multicolor flow cytometry to detect abnormal immunophenotypes and polymerase chain reaction (PCR) assays to detect clonal rearrangements in immunoglobulin heavy chain genes and/or T-cell receptor genes or fusion transcripts (e.g. BCR-ABL (Philadelphia chromosome)). The results include the descriptive summary of MRD qualitative result (positive/negative) before treatment and at Day 28 after treatment and before HSCT by local assessment (flow cytometry). | Enrollment/Pre-chemotherapy and Day 28 |
| Bone Marrow Minimum Residual Disease (MRD) Status by qPCR on Day 28 Post CTL019 Infusion | MRD in ALL refers to the presence of leukemic cells below the threshold of detection using conventional morphologic methods. The most frequently used methods for MRD assessment include multicolor flow cytometry to detect abnormal immunophenotypes and polymerase chain reaction (PCR) assays to detect clonal rearrangements in immunoglobulin heavy chain genes and/or T-cell receptor genes or fusion transcripts (e.g. BCR-ABL (Philadelphia chromosome)). The results include the descriptive summary of MRD qualitative result (positive/negative) before treatment and at Day 28 after treatment and before HSCT by local assessment (qPCR). | Enrollment/Pre-chemotherapy and Day 28 |
| Incidence of Immunogenicity Against CTL019 - Humoral Immunogenicity | The humoral immunogenicity assessment included evaluation of pre-existing (pre-treatment) and post-treatment anti-CTL019 antibodies to examine the incidence of immunogenicity with treatment. | Baseline, Day 14, Day 28, Month 3, Month 6 and Month 12 |
| Incidence of Immunogenicity Against CTL019 - Cellular Immunogenicity | The cellular immunogenicity assessment included percentage of CD4+ and CD8+ T- cells specific for CTL019. | Baseline, Day 14, Day 28, Month 3, Month 6 and Month 12 |
| AUC0-28d: PK Parameters for CTL019 by qPCR | Area under the concentration-time curve of CTL019 in the peripheral blood after single dose administration from time zero to Day 28 after single dose administration as measured by qPCR. | Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28 |
| AUC0-84d: PK Parameters for CTL019 by qPCR | Area under the concentration-time curve of CTL019 in the peripheral blood after single dose administration from time zero to Day 84 after single dose administration as measured by qPCR. | Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28 and 84 |
| Cmax: PK Parameters for CTL019 by qPCR | The maximum (peak) observed in peripheral blood drug concentration after single dose administration | Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12 |
| Clast: PK Parameters for CTL019 by qPCR | The last observed in peripheral blood drug concentration after single dose administration. | Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12 |
| Tmax: PK Parameters for CTL019 by qPCR | The time to reach maximum (peak) peripheral blood drug concentration after single dose administration. | Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12 |
| T1/2: PK Parameters for CTL019 by qPCR | The half-life associated with the elimination phase slope of a semi logarithmic concentration-time curve (days) in peripheral blood. | Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12 |
| Tlast: PK Parameters for CTL019 by qPCR | The time to reach the last observed quantifiable concentration in peripheral blood after single dose administration. | Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12 |
| AUC0-28d by Maximum Cytokine Release Syndrome (CRS) Grade | AUC0-28d from time zero to Day 28 after single dose administration as measured by qPCR. PK results were presented by the maximum Penn Grading Scale (Grade 1 to 4):
| Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28 |
| Cmax by Maximum Cytokine Release Syndrome (CRS) Grade | The maximum (peak) observed in peripheral blood drug concentration after single dose administration. PK results were presented by the maximum Penn Grading Scale (Grade 1 to 4):
| Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12 |
| Ghent |
| 9000 |
| Belgium |
| Novartis Investigative Site | Toronto | Ontario | M5G 1X8 | Canada |
| Novartis Investigative Site | Montreal | Quebec | H3T 1C5 | Canada |
| Novartis Investigative Site | Paris | 75019 | France |
| Novartis Investigative Site | Paris | 75475 | France |
| Novartis Investigative Site | Frankfurt | 60590 | Germany |
| Novartis Investigative Site | Monza | MB | 20900 | Italy |
| Novartis Investigative Site | Kyoto | 606 8507 | Japan |
| Novartis Investigative Site | Oslo | 0424 | Norway |
| Novartis Investigative Site | Esplugues de Llobregat | Barcelona | 08950 | Spain |
| Subject/guardian decision |
|
| Lost to Follow-up |
|
| New therapy for study indication |
|
| Protocol deviation |
|
| Progressive disease |
|
| Discontinued prior to CTL019 infusion due to death |
|
| Discontinued prior to CTL019 infusion due to technical problems |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Secondary | Overall Remission Rate (ORR) | ORR is defined as the proportion of participants with a best overall disease response of Complete remission (CR) or CR with incomplete blood count recovery (CRi), where the best overall disease response is defined as the best disease response recorded from CTL019 infusion until Month 6. | Full Analysis Set (FAS) comprised of all the participants who received an infusion of CTL019 | Posted | Count of Participants | Participants | From CTL019 infusion until Month 6 |
|
|
|
| Secondary | Number of Participants Who Achieved CR or CRi at Month 6 Without Stem Cell Transplantation (SCT) | Proportion of participants who achieved CR or CRi at Month 6 without stem cell transplantation between CTL019 infusion and Month 6 response assessment | Full Analysis Set (FAS) comprised of all the participants who received an infusion of CTL019 | Posted | Count of Participants | Participants | Month 6 |
|
|
|
| Secondary | Number of Participants Who Achieved CR or CRi and Then Proceeded to Stem Cell Transplantation (SCT) While in Remission Before Month 6 Assessment | Proportion of participants who achieved CR or CRi and then proceeded to stem cell transplantation while in remission prior to Month 6 response assessment. | Full Analysis Set (FAS) comprised of all the participants who received an infusion of CTL019 | Posted | Count of Participants | Participants | From CTL019 infusion until Month 6 |
|
|
|
| Secondary | Duration of Response (DOR) | DOR is the duration of remission from the date when the response criteria of CR or CRi was first met post CTL019 infusion to the date of relapse or death due to acute lymphoblastic leukemia (ALL), whichever occured first. | Full Analysis Set (FAS) comprised of all the participants who received an infusion of CTL019 and had a best overall response of CR or CRi | Posted | Median | Full Range | Months | Actual reported Time Frame: up to 14.4 months post CTL019 infusion (planned follow-up period per protocol was only 12 months post CTL019 infusion) |
|
|
|
| Secondary | Relapse-free Survival (RFS) | RFS is measured by the time from achievement of CR or CRi whichever occured first post CTL019 infusion, to relapse or death due to any cause during CR or CRi. | Full Analysis Set (FAS) comprised of all the participants who received an infusion of CTL019 and had a best overall response of CR or CRi | Posted | Median | Full Range | Months | Actual reported Time Frame: up to 14.4 months post CTL019 infusion (planned follow-up period per protocol was only 12 months post CTL019 infusion) |
|
|
|
| Secondary | Event-free Survival (EFS) | EFS is the time from date of CTL019 infusion to the earliest of death, relapse or treatment failure. | Full Analysis Set (FAS) comprised of all the participants who received an infusion of CTL019 | Posted | Median | Full Range | Months | Actual reported Time Frame: up to 15.1 months post CTL019 infusion (planned follow-up period per protocol was only 12 months post CTL019 infusion) |
|
|
|
| Secondary | Overall Survival (OS) | OS is the time from date of CTL019 infusion to the date of death due to any reason | Full Analysis Set (FAS) comprised of all the participants who received an infusion of CTL019 | Posted | Median | Full Range | Months | Actual reported Time Frame: up to 24.4 months post CTL019 infusion (planned follow-up period per protocol was only 12 months post CTL019 infusion) |
|
|
|
| Secondary | Number of Participants Who Attained CR or CRi at Day 28 | Proportion of participants who attained CR or CRi at Day 28 post CTL019 infusion. | Full Analysis Set (FAS) comprised of all the participants who received an infusion of CTL019 | Posted | Count of Participants | Participants | Day 28 |
|
|
|
| Secondary | Number of Participants Who Attained CR or CRi at Day 28 by Baseline Bone Marrow Tumor Burden | Proportion of participants who attained CR or CRi at Day 28 post CTL019 infusion by baseline bone marrow tumor burden. | Full Analysis Set (FAS) comprised of all the participants who received an infusion of CTL019 and had a baseline bone marrow tumor burden result | Posted | Count of Participants | Participants | Day 28 |
|
|
|
| Secondary | Bone Marrow Minimum Residual Disease (MRD) Status by Flow Cytometry on Day 28 Post CTL019 Infusion | MRD in ALL refers to the presence of leukemic cells below the threshold of detection using conventional morphologic methods. The most frequently used methods for MRD assessment include multicolor flow cytometry to detect abnormal immunophenotypes and polymerase chain reaction (PCR) assays to detect clonal rearrangements in immunoglobulin heavy chain genes and/or T-cell receptor genes or fusion transcripts (e.g. BCR-ABL (Philadelphia chromosome)). The results include the descriptive summary of MRD qualitative result (positive/negative) before treatment and at Day 28 after treatment and before HSCT by local assessment (flow cytometry). | Full Analysis Set (FAS) comprised of all the participants who received an infusion of CTL019 | Posted | Count of Participants | Participants | Enrollment/Pre-chemotherapy and Day 28 |
|
|
|
| Secondary | Bone Marrow Minimum Residual Disease (MRD) Status by qPCR on Day 28 Post CTL019 Infusion | MRD in ALL refers to the presence of leukemic cells below the threshold of detection using conventional morphologic methods. The most frequently used methods for MRD assessment include multicolor flow cytometry to detect abnormal immunophenotypes and polymerase chain reaction (PCR) assays to detect clonal rearrangements in immunoglobulin heavy chain genes and/or T-cell receptor genes or fusion transcripts (e.g. BCR-ABL (Philadelphia chromosome)). The results include the descriptive summary of MRD qualitative result (positive/negative) before treatment and at Day 28 after treatment and before HSCT by local assessment (qPCR). | Full Analysis Set (FAS) comprised of all the participants who received an infusion of CTL019 | Posted | Count of Participants | Participants | Enrollment/Pre-chemotherapy and Day 28 |
|
|
|
| Secondary | Incidence of Immunogenicity Against CTL019 - Humoral Immunogenicity | The humoral immunogenicity assessment included evaluation of pre-existing (pre-treatment) and post-treatment anti-CTL019 antibodies to examine the incidence of immunogenicity with treatment. | The Safety Set (SAF) comprised of all the participants who received an infusion of CTL019 | Posted | Count of Participants | Participants | Baseline, Day 14, Day 28, Month 3, Month 6 and Month 12 |
|
|
|
| Secondary | Incidence of Immunogenicity Against CTL019 - Cellular Immunogenicity | The cellular immunogenicity assessment included percentage of CD4+ and CD8+ T- cells specific for CTL019. | The Safety Set (SAF) comprised of all the participants who received an infusion of CTL019 | Posted | Count of Participants | Participants | Baseline, Day 14, Day 28, Month 3, Month 6 and Month 12 |
|
|
|
| Secondary | AUC0-28d: PK Parameters for CTL019 by qPCR | Area under the concentration-time curve of CTL019 in the peripheral blood after single dose administration from time zero to Day 28 after single dose administration as measured by qPCR. | Cellular kinetic analysis set (CKAS) consisted of participants in the FAS who had at least 1 sample providing evaluable cellular kinetic data and had non-missing data | Posted | Geometric Mean | Geometric Coefficient of Variation | copies/ug*day | Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28 |
|
|
|
| Secondary | AUC0-84d: PK Parameters for CTL019 by qPCR | Area under the concentration-time curve of CTL019 in the peripheral blood after single dose administration from time zero to Day 84 after single dose administration as measured by qPCR. | Cellular kinetic analysis set (CKAS) consisted of participants in the FAS who had at least 1 sample providing evaluable cellular kinetic data and had non-missing data | Posted | Geometric Mean | Geometric Coefficient of Variation | Copies/ug*day | Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28 and 84 |
|
|
|
| Secondary | Cmax: PK Parameters for CTL019 by qPCR | The maximum (peak) observed in peripheral blood drug concentration after single dose administration | Cellular kinetic analysis set (CKAS) consisted of participants in the FAS who had at least 1 sample providing evaluable cellular kinetic data and had non-missing data | Posted | Geometric Mean | Geometric Coefficient of Variation | copies/ug | Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12 |
|
|
|
| Secondary | Clast: PK Parameters for CTL019 by qPCR | The last observed in peripheral blood drug concentration after single dose administration. | Cellular kinetic analysis set (CKAS) consisted of participants in the FAS who had at least 1 sample providing evaluable cellular kinetic data and had non-missing data | Posted | Geometric Mean | Geometric Coefficient of Variation | copies/ug | Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12 |
|
|
|
| Secondary | Tmax: PK Parameters for CTL019 by qPCR | The time to reach maximum (peak) peripheral blood drug concentration after single dose administration. | Cellular kinetic analysis set (CKAS) consisted of participants in the FAS who had at least 1 sample providing evaluable cellular kinetic data and had non-missing data | Posted | Median | Full Range | days | Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12 |
|
|
|
| Secondary | T1/2: PK Parameters for CTL019 by qPCR | The half-life associated with the elimination phase slope of a semi logarithmic concentration-time curve (days) in peripheral blood. | Cellular kinetic analysis set (CKAS) consisted of participants in the FAS who had at least 1 sample providing evaluable cellular kinetic data and had non-missing data | Posted | Geometric Mean | Geometric Coefficient of Variation | days | Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12 |
|
|
|
| Secondary | Tlast: PK Parameters for CTL019 by qPCR | The time to reach the last observed quantifiable concentration in peripheral blood after single dose administration. | Cellular kinetic analysis set (CKAS) consisted of participants in the FAS who had at least 1 sample providing evaluable cellular kinetic data and had non-missing data | Posted | Median | Full Range | days | Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12 |
|
|
|
| Secondary | AUC0-28d by Maximum Cytokine Release Syndrome (CRS) Grade | AUC0-28d from time zero to Day 28 after single dose administration as measured by qPCR. PK results were presented by the maximum Penn Grading Scale (Grade 1 to 4):
| Cellular kinetic analysis set (CKAS) consisted of participants in the FAS who had at least 1 sample providing evaluable cellular kinetic data and had non-missing data | Posted | Geometric Mean | Geometric Coefficient of Variation | copies/ug*day | Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28 |
|
|
|
| Secondary | Cmax by Maximum Cytokine Release Syndrome (CRS) Grade | The maximum (peak) observed in peripheral blood drug concentration after single dose administration. PK results were presented by the maximum Penn Grading Scale (Grade 1 to 4):
| Cellular kinetic analysis set (CKAS) consisted of participants in the FAS who had at least 1 sample providing evaluable cellular kinetic data and had non-missing data | Posted | Geometric Mean | Geometric Coefficient of Variation | copies/ug | Day 1 10 min post-infusion, Day 4, 7, 11, 14, 28, Month 3, 6, 9 and 12 |
|
|
|
| Post-Hoc | Total Number of Deaths | Deaths were reported in the pre-treatment period (without receiving a CTL019 infusion) and post-treatment period (after receiving a CTL019 infusion). | all enrolled participants | Posted | Number | Participants | Pre-treatment period: up to 81 days post signed informed consent; Post-treatment period: up to 24.4 months post CTL019 infusion (planned follow-up period per protocol was only 12 months post CTL019 infusion) |
|
|
|
| 9 |
| 69 |
| 50 |
| 69 |
| 66 |
| 69 |
| Bone marrow failure | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Left ventricular dysfunction | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Drug withdrawal syndrome | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Multiple organ dysfunction syndrome | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hepatocellular injury | Hepatobiliary disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hepatosplenomegaly | Hepatobiliary disorders | MedDRA (23.1) | Systematic Assessment |
|
| Cytokine release syndrome | Immune system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Haemophagocytic lymphohistiocytosis | Immune system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Alternaria infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Aspergillus infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Bacterial infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Candida infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Cellulitis orbital | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Central nervous system infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Cerebral fungal infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Device related infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Enterococcal infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Meningitis aseptic | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Periorbital cellulitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Pneumonia haemophilus | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Respiratory syncytial virus infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Septic shock | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Tonsillitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Splinter | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment |
|
| Blood fibrinogen decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Chest X-ray abnormal | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Immunoglobulins decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
|
| Lactic acidosis | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
|
| Tumour lysis syndrome | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Joint effusion | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Acute lymphocytic leukaemia recurrent | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.1) | Systematic Assessment |
|
| B precursor type acute leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.1) | Systematic Assessment |
|
| Leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.1) | Systematic Assessment |
|
| Neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.1) | Systematic Assessment |
|
| Depressed level of consciousness | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Dysarthria | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Dyskinesia | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Encephalopathy | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Facial paralysis | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Seizure | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA (23.1) | Systematic Assessment |
|
| Completed suicide | Psychiatric disorders | MedDRA (23.1) | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA (23.1) | Systematic Assessment |
|
| Disorientation | Psychiatric disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hallucination | Psychiatric disorders | MedDRA (23.1) | Systematic Assessment |
|
| Irritability | Psychiatric disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Jugular vein thrombosis | Vascular disorders | MedDRA (23.1) | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (23.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Chills | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Face oedema | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (23.1) | Systematic Assessment |
|
| Allergy to immunoglobulin therapy | Immune system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Cytokine release syndrome | Immune system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hypogammaglobulinaemia | Immune system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Blood fibrinogen decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Immunoglobulins decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA (23.1) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Seizure | Nervous system disorders | MedDRA (23.1) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (23.1) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (23.1) | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA (23.1) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (23.1) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (23.1) | Systematic Assessment |
|
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 (ie, data from all sites) in the clinical trial.
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Not done |
|
| Missing |
|
| Day 28 |
|
| Not done |
|
| Missing |
|
| Day 28 |
|
| Day 14 |
|
| Day 28 |
|
| Month 3 |
|
| Month 6 |
|
| Month 12 |
|
| Title | Measurements |
|---|---|
|
| CTL019 Pool 1 CD3+ CD4+ IFNg+ Month 3 |
|
| CTL019 Pool 1 CD3+ CD4+ IFNg+ Month 6 |
|
| CTL019 Pool 1 CD3+ CD4+ IFNg+ Month 12 |
|
| CTL019 Pool 2 CD3+ CD4+ IFNg+ Baseline |
|
| CTL019 Pool 2 CD3+ CD4+ IFNg+ Day 14 |
|
| CTL019 Pool 2 CD3+ CD4+ IFNg+ Day 28 |
|
| CTL019 Pool 2 CD3+ CD4+ IFNg+ Month 3 |
|
| CTL019 Pool 2 CD3+ CD4+ IFNg+ Month 6 |
|
| CTL019 Pool 2 CD3+ CD4+ IFNg+ Month 12 |
|
| CTL019 Pool 1 CD3+ CD8+ IFNg+ Baseline |
|
| CTL019 Pool 1 CD3+ CD8+ IFNg+ Day 14 |
|
| CTL019 Pool 1 CD3+ CD8+ IFNg+ Day 28 |
|
| CTL019 Pool 1 CD3+ CD8+ IFNg+ Month 3 |
|
| CTL019 Pool 1 CD3+ CD8+ IFNg+ Month 6 |
|
| CTL019 Pool 1 CD3+ CD8+ IFNg+ Month 12 |
|
| CTL019 Pool 2 CD3+ CD8+ IFNg+ Baseline |
|
| CTL019 Pool 2 CD3+ CD8+ IFNg+ Day 14 |
|
| CTL019 Pool 2 CD3+ CD8+ IFNg+ Day 28 |
|
| CTL019 Pool 2 CD3+ CD8+ IFNg+ Month 3 |
|
| CTL019 Pool 2 CD3+ CD8+ IFNg+ Month 6 |
|
| CTL019 Pool 2 CD3+ CD8+ IFNg+ Month 12 |
|
|
| Grade 3 |
|
|
| Grade 4 |
|
|
|
| Grade 3 |
|
|
| Grade 4 |
|
|
|
| Post-treatment: >30 days (after CTL019 infusion) |
|
|