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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-005019-15 | EudraCT Number |
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The purpose of the study was to assess the efficacy and safety of tisagenlecleucel in pediatric, adolescent and young adult patients with relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL) including Burkitt Lymphoma and Burkitt Leukemia.
For pediatric patients who have r/r B-NHL including Burkitt Lymphoma and Burkitt Leukemia, survival rates are dismal, only ~20-50% subjects are alive at 2 years with overall response rate (ORR) of 20-30% after conventional salvage chemotherapy.
This study was part of an agreed Pediatric Investigation Plan (PIP). The single-arm study design included r/r B-cell NHL including Burkitt Lymphoma and Burkitt Leukemia subject population with poor prognosis, lack of approved effective therapies in this setting. Subject population included aggressive subtypes of B-cell NHL including Burkitt Lymphoma and Burkitt Leukemia who were allowed to receive "bridging therapy" of investigator's choice. After assessment of eligibility, subjects qualifying for the study were enrolled and were allowed to start lymphodepleting chemotherapy as recommended in protocol after which a single dose of tisagenlecleucel product was infused. The efficacy of tisagenlecleucel was evaluated through the primary endpoint of Overall Response Rate (ORR) which included complete response (CR) and partial response (PR) as determined by local assessment. Safety assessments were conducted until study completion.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tisagenlecleucel | Experimental | Participants were infused once with CAR-positive viable T cells |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tisagenlecleucel | Biological | Tisagenlecleucel was infused once as an intravenous infustion at a dose of either 0.2 to 5 x 106 CAR-positive viable T cells per kg body weight for subjects ≤ 50 kg or 0.1 to 2.5 x 108 CAR-positive viable T cells for subjects > 50 kg. |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate (ORR) as Determined by Local Investigator | The overall response rate (ORR) is defined as the percentage of subjects with a best overall disease response of complete response (CR) or partial response (PR), where the best overall disease response is defined as the best disease response recorded from tisagenlecleucel infusion until progressive disease or start of new anticancer therapy, whichever comes first. | 6 months post-tisagenlecleucel infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of Response (DOR) | Duration of response (DOR) is defined as the time from the date of first documented disease response (CR or PR) as determined by local investigator assessments to the date of first documented progression or death due to underlying cancer. | Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48 |
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Inclusion Criteria:
Histologically confirmed pediatric mature B-cell non-Hodgkin lymphoma (B-cell NHL) including the following subtypes; Burkitt lymphoma/ Burkitt leukemia (BL), diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), gray zone lymphoma (GZL), and follicular lymphoma (FL) Note: Patients with B-cell NHL associated with Nijmegen breakage syndrome will be allowed.
Patients <25 years of age and weighing at least 6 kg at the time of screening
Patients who have relapsed after one or more prior therapies (can include allogeneic and autologous hematopoietic stem cell transplant) or are primary refractory (have not achieved a CR or PR after the first line of therapy)
Measurable disease by radiological criteria in all patients at the time of screening. Patients with Burkitt leukemia who don't meet radiological criteria must have bone marrow involvement of >25% by local assessment of bone marrow aspirate and/or biopsy.
Karnofsky (age ≥16 years) or Lansky (age <16 years) performance status ≥60.
Adequate bone marrow reserve without transfusions (transfusion >2 weeks prior to laboratory assessment is allowed) defined as:
Adequate organ function defined as:
a serum creatinine (sCR) based on gender/age as follows: Maximum Serum Creatinine (mg/dL) Age Male Female
1 to <2 years 0.6 0.6 2 to <6 years 0.8 0.8 6 to <10 years 1.0 1.0 10 to <13 years 1.2 1.2 13 to <16 years 1.5 1.4
≥16 years 1.7 1.4
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 times the upper limit of normal (ULN) for age
Total bilirubin <2 mg/dL (for Gilbert's Syndrome patients total bilirubin <4 mg/dL)
Adequate pulmonary function
i. Oxygen saturation of >91% on room air ii. No or mild dyspnea (≤Grade 1)
Must have a leukapheresis material of non-mobilized cells accepted for manufacturing.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Childrens Hospital Los Angeles | Los Angeles | California | 90027 | United States | ||
| UCSF Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34515338 | Derived | Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2. |
| Label | URL |
|---|---|
| Patient Lay Trial Summary | View source |
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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 expert 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 is currently available according to the process described on www.clinicalstudydatarequest.com.
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Consent, Screening, Pre-treatment, Treatment and Follow-up. In the Pretreatment phase, the subject may have undergone optional bridging therapy or lymphodepleting chemotherapy. Full Analysis Set: 33 Efficacy Analysis Set (EAS): 28; 4 patients with Complete Response prior to infusion & 1 without a scan prior to infusion excluded from EAS.
This study was conducted in twenty-four centers across 14 countries. Although 34 participants met the eligibility criteria and apheresis was accepted by the manufacturing facility, only 33 were infused in the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tisagenlecleucel | These participants were infused once with CAR-positive viable T cells. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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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 | Jan 14, 2020 | Oct 25, 2023 |
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|
| lymphodepleting chemotherapy | Drug | Prior to tisagenlecleucel infusion, each subject underwent lymphodepletion with recommended Fludarabine and cyclophosphamide (unless contra-indicated for subject) |
|
| Bridging Therapy | Drug | Pre-treatment phase could also include bridging therapy of investigator's choice |
|
| Event Free Survival (EFS) | Event free survival (EFS) is defined as the time from date of first tisagenlecleucel infusion to the earliest date of death from any cause, disease progression as determined by local investigator assessments, or starting new anticancer therapy for underlying cancer, excluding hematopoietic stem cell transplant (HSCT). | Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48 |
| Relapse Free Survival (RFS) | Relapse free survival (RFS) is defined as the time from the date of first documented disease response (CR or PR) as determined by local investigator assessments to the date of first documented disease progression or death due to any cause. | Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48 |
| Progression Free Survival (PFS) | Progression free survival (PFS) is defined as the time from the date of first tisagenlecleucel infusion to the date of first documented disease progression as determined by local investigator assessments or death due to any cause. Progression is defined using the International non-Hodgkin Lymphoma Response Criteria. For a PET-based response, progressive disease is defined as a 4 or 5 on the 5 point scale with increased uptake compared to the nadir or new FDG-avid foci consistent with lymphoma. For a CT/MRI based response progressive disease is defined as a 25% increase in the SPD (sum of the products of two largest perpendicular diameters) of index lesions, or unequivocal progression in either non-index lesions or the spleen. Any new disease attributable to lymphoma would also constitute progressive disease. | Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48 |
| Overall Survival (OS) | Overall survival (OS) is defined as the time from date of first tisagenlecleucel infusion to the date of death due to any cause. | Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48 |
| Cellular Kinetics Parameter: Cmax | The maximum (peak) transgene level (copies/μg) observed in peripheral blood or other body fluid after single dose administration as measured by qPCR. Pharmacokinetics of tisagenlecleucel were based on chimeric antigen receptor (CAR) transgene levels in peripheral blood as detected by qPCR, unless otherwise noted. Pharmacokinetics of tisagenlecleucel were based on chimeric antigen receptor (CAR) transgene levels in peripheral blood as detected by qPCR, unless otherwise noted. | Post-infusion day 4, day 7, day 11, day 14, day 21, day 28, month 3, month 6, month 9, month 12, month 18, month 24, and then annually until Month 48 |
| Cellular Kinetics Parameter: Tmax | The time to reach maximum (peak) transgene level (days) in peripheral blood or other body fluid after single dose administration. Pharmacokinetics of tisagenlecleucel were based on chimeric antigen receptor (CAR) transgene levels in peripheral blood as detected by qPCR, unless otherwise noted. | Post-infusion day 4, day 7, day 11, day 14, day 21, day 28, month 3, month 6, month 9, month 12, month 18, month 24, and then annually until Month 48 |
| Cellular Kinetics Parameter: AUC0-28d | Area Under the Concentration-time Curve (AUCs) from the time course of transgene levels in peripheral blood following tisagenlecleucel infusion (days*copies/μg), from day of infusion to day 28. D28 refers to the timepoint for definition of responder populations. Pharmacokinetics of tisagenlecleucel were based on chimeric antigen receptor (CAR) transgene levels in peripheral blood as detected by qPCR, unless otherwise noted. | 0 to 28 days |
| Cellular Kinetics Parameter: Clast | The last observed quantifiable transgene level in peripheral blood. Pharmacokinetics of tisagenlecleucel were based on chimeric antigen receptor (CAR) transgene levels in peripheral blood as detected by qPCR, unless otherwise noted. | Post-infusion day 4, day 7, day 11, day 14, day 21, day 28, month 3, month 6, month 9, month 12, month 18, month 24, and then annually until Month 48 |
| Cellular Kinetics Parameter: Tlast | The time of last observed quantifiable transgene level in peripheral blood. Pharmacokinetics of tisagenlecleucel were based on chimeric antigen receptor (CAR) transgene levels in peripheral blood as detected by qPCR, unless otherwise noted. | Post-infusion day 4, day 7, day 11, day 14, day 21, day 28, month 3, month 6, month 9, month 12, month 18, month 24, and then annually until Month 48 |
| Levels of Pre-existing and Treatment Induced Humoral Immunogenicity and Cellular Immunogenicity Against Tisagenlecleucel Cellular Kinetics, Safety and Efficacy | The humoral immunogenicity assay measures the antibody titers specific to tisagenlecleucel prior to and following infusion by flow cytometry. A subject was only defined as positive for tisagenlecleucel treatment-induced or -boosted anti-mCAR19 antibodies when the anti-mCAR19 antibody median fluorescence intensity at any time post-infusion was at least 2.28-fold higher (for samples analyzed on or prior to 05-May-2021) or 2.38-fold higher (for samples analyzed on or after 06-May-2021) than pre-infusion levels for participants whose baseline status was positive (boosted) or if the baseline status was negative but any post-baseline interpretation was positive (induced). | Until disease progression or through study completion, up to 4 years |
| Percentage of Participants Who Proceeded to Stem Cell Transplant (SCT) After Tisagenlecleucel Infusion | These participants proceeded to transplant any time post-tisagenlecleucel therapy until end of study (EOS). | Through study completion, up to 4 years |
| Maximum Positive Predictive Value (PPV) | Retrospective assessment of potential cytokine release syndrome (CRS) predictive models considering also data from other CTL019 trials. The Positive Predictive Value (PVV) is the percentage of participants who actually had severe CRS out of all the cases where the prediction model predicts that severe CRS will occur. The maximum PPV is the highest value attained across all potential CRS predictive models. | Through study completion, up to 4 years |
| San Francisco |
| California |
| 94143 |
| United States |
| Johns Hopkins Oncology Center ORA | Baltimore | Maryland | 21231 | United States |
| Dana Farber Cancer Institute Dept.of DFCI | Boston | Massachusetts | 02215 | United States |
| Memorial Sloan Kettering Cancer Center MSKCC (8) | New York | New York | 10065 | United States |
| Cinn Children Hosp Medical Center | Cincinnati | Ohio | 45229-3039 | United States |
| The Childrens Hospital of Philadelphia Drug Shipment | Philadelphia | Pennsylvania | 19104 | United States |
| University of Texas Southwestern Medical Center . | Dallas | Texas | 75235 | United States |
| Novartis Investigative Site | Randwick | New South Wales | 2031 | Australia |
| Novartis Investigative Site | Parkville | Victoria | 3052 | Australia |
| Novartis Investigative Site | Vienna | A 1090 | Austria |
| Novartis Investigative Site | Toronto | Ontario | M5G 1X8 | Canada |
| Novartis Investigative Site | Copenhagen | 2100 | Denmark |
| Novartis Investigative Site | Helsinki | 00029 | Finland |
| Novartis Investigative Site | Paris | 75019 | France |
| Novartis Investigative Site | Villejuif | 94800 | France |
| Novartis Investigative Site | Münster | 48149 | Germany |
| Novartis Investigative Site | Monza | MB | 20900 | Italy |
| Novartis Investigative Site | Roma | RM | 00165 | Italy |
| Kyoto University Hospital | Sakyō-ku | Kyoto | 606 8507 | Japan |
| Novartis Investigative Site | Setagaya-ku | Tokyo | 157-8535 | Japan |
| Prinses Maxima Centrum voor Kinderoncologie | Utrecht | CS | 3584 | Netherlands |
| Novartis Investigative Site | Oslo | 0424 | Norway |
| Novartis Investigative Site | Barcelona | Catalonia | 08035 | Spain |
| Novartis Investigative Site | Madrid | 28046 | Spain |
| Novartis Investigative Site | London | WC1N 1EH | United Kingdom |
| Met Eligibilty Criteria and Were Infused |
|
| Met Eligibilty Criteria But Was Not Infused* | *Patient died prior to infusion |
|
| Completed Treatment & Primary Follow-up Phase |
|
| Discont. Treatment & Primary Follow-up Phase |
|
| COMPLETED |
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| NOT COMPLETED |
|
|
FAS and safety set: all subjects who received an infusion of tisagenlecleucel
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| ID | Title | Description |
|---|---|---|
| BG000 | Tisagenlecleucel | These participants were infused once with CAR-positive viable T cells. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Standard Deviation | years |
| ||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Race/Ethnicity, Customized | Number | Participants | No |
| ||||||||||||||||||||||
| Histology (type of lymphoma) | Count of Participants | Participants |
|
| 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 | Overall Response Rate (ORR) as Determined by Local Investigator | The overall response rate (ORR) is defined as the percentage of subjects with a best overall disease response of complete response (CR) or partial response (PR), where the best overall disease response is defined as the best disease response recorded from tisagenlecleucel infusion until progressive disease or start of new anticancer therapy, whichever comes first. | Efficacy Analysis Set (EAS): all subjects with aggressive r/r B-cell NHL who received an infusion of tisagenlecleucel and had measurable disease at baseline, i.e participants with complete or unknown response after bridging therapy were excluded from the efficacy analysis set. | Posted | Number | 95% Confidence Interval | Percentage of participants | 6 months post-tisagenlecleucel infusion |
|
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| Secondary | Duration of Response (DOR) | Duration of response (DOR) is defined as the time from the date of first documented disease response (CR or PR) as determined by local investigator assessments to the date of first documented progression or death due to underlying cancer. | EAS: all subjects with aggressive r/r B-cell NHL who received an infusion of tisagenlecleucel and had measurable disease at baseline. Only participants with best response of CR/PR post-infusion were included in the DOR analysis. | Posted | Median | 95% Confidence Interval | months | Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48 |
|
| ||||||||||||||||||||||||||
| Secondary | Event Free Survival (EFS) | Event free survival (EFS) is defined as the time from date of first tisagenlecleucel infusion to the earliest date of death from any cause, disease progression as determined by local investigator assessments, or starting new anticancer therapy for underlying cancer, excluding hematopoietic stem cell transplant (HSCT). | EAS: all subjects with aggressive r/r B-cell NHL who received an infusion of tisagenlecleucel and had measurable disease at baseline, i.e participants with complete or unknown response after bridging therapy were excluded from the efficacy analysis set. | Posted | Median | 95% Confidence Interval | months | Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48 |
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| Secondary | Relapse Free Survival (RFS) | Relapse free survival (RFS) is defined as the time from the date of first documented disease response (CR or PR) as determined by local investigator assessments to the date of first documented disease progression or death due to any cause. | EAS: all subjects with aggressive r/r B-cell NHL who received an infusion of tisagenlecleucel and had measurable disease at baseline. Only participants with best response of CR/PR post-infusion were included in the RFS analysis. | Posted | Median | 95% Confidence Interval | months | Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48 |
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| Secondary | Progression Free Survival (PFS) | Progression free survival (PFS) is defined as the time from the date of first tisagenlecleucel infusion to the date of first documented disease progression as determined by local investigator assessments or death due to any cause. Progression is defined using the International non-Hodgkin Lymphoma Response Criteria. For a PET-based response, progressive disease is defined as a 4 or 5 on the 5 point scale with increased uptake compared to the nadir or new FDG-avid foci consistent with lymphoma. For a CT/MRI based response progressive disease is defined as a 25% increase in the SPD (sum of the products of two largest perpendicular diameters) of index lesions, or unequivocal progression in either non-index lesions or the spleen. Any new disease attributable to lymphoma would also constitute progressive disease. | EAS: all subjects with aggressive r/r B-cell NHL who received an infusion of tisagenlecleucel and had measurable disease at baseline, i.e participants with complete or unknown response after bridging therapy were excluded from the efficacy analysis set. | Posted | Median | 95% Confidence Interval | months | Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48 |
|
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| Secondary | Overall Survival (OS) | Overall survival (OS) is defined as the time from date of first tisagenlecleucel infusion to the date of death due to any cause. | EAS: all subjects with aggressive r/r B-cell NHL who received an infusion of tisagenlecleucel and had measurable disease at baseline, i.e participants with complete or unknown response after bridging therapy were excluded from the efficacy analysis set. | Posted | Median | 95% Confidence Interval | months | Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48 |
|
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| Secondary | Cellular Kinetics Parameter: Cmax | The maximum (peak) transgene level (copies/μg) observed in peripheral blood or other body fluid after single dose administration as measured by qPCR. Pharmacokinetics of tisagenlecleucel were based on chimeric antigen receptor (CAR) transgene levels in peripheral blood as detected by qPCR, unless otherwise noted. Pharmacokinetics of tisagenlecleucel were based on chimeric antigen receptor (CAR) transgene levels in peripheral blood as detected by qPCR, unless otherwise noted. | Cellular kinetic analysis set (CKAS): subjects in the FAS who provided at least 1 valid cellular kinetic concentration for tisagenlecleucel. Certain PK parameters were not estimable for all subjects due to insufficient samples. | Posted | Geometric Mean | Geometric Coefficient of Variation | copies/μg | Post-infusion day 4, day 7, day 11, day 14, day 21, day 28, month 3, month 6, month 9, month 12, month 18, month 24, and then annually until Month 48 |
|
| ||||||||||||||||||||||||||
| Secondary | Cellular Kinetics Parameter: Tmax | The time to reach maximum (peak) transgene level (days) in peripheral blood or other body fluid after single dose administration. Pharmacokinetics of tisagenlecleucel were based on chimeric antigen receptor (CAR) transgene levels in peripheral blood as detected by qPCR, unless otherwise noted. | CKAS: subjects in the FAS who provided at least 1 valid cellular kinetic concentration for tisagenlecleucel. Certain PK parameters were not estimable for all subjects due to insufficient samples. | Posted | Median | Full Range | days | Post-infusion day 4, day 7, day 11, day 14, day 21, day 28, month 3, month 6, month 9, month 12, month 18, month 24, and then annually until Month 48 |
|
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| Secondary | Cellular Kinetics Parameter: AUC0-28d | Area Under the Concentration-time Curve (AUCs) from the time course of transgene levels in peripheral blood following tisagenlecleucel infusion (days*copies/μg), from day of infusion to day 28. D28 refers to the timepoint for definition of responder populations. Pharmacokinetics of tisagenlecleucel were based on chimeric antigen receptor (CAR) transgene levels in peripheral blood as detected by qPCR, unless otherwise noted. | CKAS: subjects in the FAS who provided at least 1 valid cellular kinetic concentration for tisagenlecleucel. Certain PK parameters were not estimable for all subjects due to insufficient samples. | Posted | Geometric Mean | Geometric Coefficient of Variation | copies/μg*days | 0 to 28 days |
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| Secondary | Cellular Kinetics Parameter: Clast | The last observed quantifiable transgene level in peripheral blood. Pharmacokinetics of tisagenlecleucel were based on chimeric antigen receptor (CAR) transgene levels in peripheral blood as detected by qPCR, unless otherwise noted. | CKAS: subjects in the FAS who provided at least 1 valid cellular kinetic concentration for tisagenlecleucel. Certain PK parameters were not estimable for all subjects due to insufficient samples. | Posted | Geometric Mean | Geometric Coefficient of Variation | copies/μg | Post-infusion day 4, day 7, day 11, day 14, day 21, day 28, month 3, month 6, month 9, month 12, month 18, month 24, and then annually until Month 48 |
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| Secondary | Cellular Kinetics Parameter: Tlast | The time of last observed quantifiable transgene level in peripheral blood. Pharmacokinetics of tisagenlecleucel were based on chimeric antigen receptor (CAR) transgene levels in peripheral blood as detected by qPCR, unless otherwise noted. | CKAS: subjects in the FAS who provided at least 1 valid cellular kinetic concentration for tisagenlecleucel. Certain PK parameters were not estimable for all subjects due to insufficient samples. | Posted | Median | Full Range | days | Post-infusion day 4, day 7, day 11, day 14, day 21, day 28, month 3, month 6, month 9, month 12, month 18, month 24, and then annually until Month 48 |
|
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| Secondary | Levels of Pre-existing and Treatment Induced Humoral Immunogenicity and Cellular Immunogenicity Against Tisagenlecleucel Cellular Kinetics, Safety and Efficacy | The humoral immunogenicity assay measures the antibody titers specific to tisagenlecleucel prior to and following infusion by flow cytometry. A subject was only defined as positive for tisagenlecleucel treatment-induced or -boosted anti-mCAR19 antibodies when the anti-mCAR19 antibody median fluorescence intensity at any time post-infusion was at least 2.28-fold higher (for samples analyzed on or prior to 05-May-2021) or 2.38-fold higher (for samples analyzed on or after 06-May-2021) than pre-infusion levels for participants whose baseline status was positive (boosted) or if the baseline status was negative but any post-baseline interpretation was positive (induced). | Safety set: All participants who received an infusion of tisagenlecleucel | Posted | Number | Percentage of participants | Until disease progression or through study completion, up to 4 years |
|
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| Secondary | Percentage of Participants Who Proceeded to Stem Cell Transplant (SCT) After Tisagenlecleucel Infusion | These participants proceeded to transplant any time post-tisagenlecleucel therapy until end of study (EOS). | Safety set: All participants who received an infusion of tisagenlecleucel | Posted | Number | Percentage of participants | Through study completion, up to 4 years |
|
| |||||||||||||||||||||||||||
| Secondary | Maximum Positive Predictive Value (PPV) | Retrospective assessment of potential cytokine release syndrome (CRS) predictive models considering also data from other CTL019 trials. The Positive Predictive Value (PVV) is the percentage of participants who actually had severe CRS out of all the cases where the prediction model predicts that severe CRS will occur. The maximum PPV is the highest value attained across all potential CRS predictive models. | Safety set: All participants who received an infusion of tisagenlecleucel | Posted | Number | Percentage of participants | Through study completion, up to 4 years |
|
| |||||||||||||||||||||||||||
| Post-Hoc | All Collected Deaths | On-treatment deaths were collected during the post-infusion period starting at the day of first infusion until the end of the study, up to 48 months. All deaths is the sum of pre-infusion and post-infusion deaths. | Clinical Database Population: All infused and non-infused participants who met the criteria to be enrolled in the study | Posted | Number | Participants | Pre-treatment deaths: from enrollment to pre-infusion; On-treatment deaths: post-infusion up to 48 months |
|
|
Adverse Event (AE) timeframe: AEs were collected during the post-infusion period (starting at the day of 1st infusion until the end of the study), up to maximum duration of 48 months for each patient. Deaths were collected at all points: pre-infusion period and post-infusion period until the patient completed the study duration (48 months) or further safety follow-up under the study protocol. Therefore on-treatment deaths include post-infusion deaths until Last patient Last Visit (LPLV)
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) and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events while still included in the All-Cause Mortality table.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tisagenlecleucel - Post-infusion | AEs/deaths collected during and post- infusion until patient completed study. | 17 | 33 | 24 | 33 | 33 | 33 |
| EG001 | Tisagenlecleucel - Pre-infusion Deaths | Deaths collected prior to infusion. No AEs were collected during this period. | 1 | 34 | 0 | 0 | 0 | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Large intestinal obstruction | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Proctitis | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Condition aggravated | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Disease progression | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Cytokine release syndrome | Immune system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Haemophagocytic lymphohistiocytosis | Immune system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Aspergillus infection | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Candida infection | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Pseudomonas infection | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Vascular device infection | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Depressed level of consciousness | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Disturbance in attention | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Memory impairment | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Motor dysfunction | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Peripheral sensorimotor neuropathy | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (26.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Bone marrow failure | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Coagulopathy | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Catheter site pain | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Chills | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Generalised oedema | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Cytokine release syndrome | Immune system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hypogammaglobulinaemia | Immune system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Myelitis | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (26.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| SARS-CoV-2 test positive | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Serum ferritin increased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Depressed level of consciousness | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Neuralgia | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (26.0) | 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 pooled data (i.e., data from all sites) in clinical trial or disclosure of trial results in their entirety.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | novartis.email@novartis.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 17, 2023 | Oct 25, 2023 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D016393 | Lymphoma, B-Cell |
| D002051 | Burkitt Lymphoma |
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| D008224 | Lymphoma, Follicular |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D020031 | Epstein-Barr Virus Infections |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D014412 | Tumor Virus Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| C000626284 | tisagenlecleucel |
Not provided
Not provided
Not provided
| Asian |
|
| Missing |
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| Participants |
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| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
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