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NCT02435849: ELIANA

Study of Efficacy and Safety of CTL019 in Pediatric ALL Patients

Completed Phase 2 Results posted Last updated 13 February 2024
What this trial tests

Phase 2 trial testing CTL019 in B-cell Acute Lymphoblastic Leukemia in 80 participants. Completed in 17 November 2022.

Timeline
8 April 2015
Primary endpoint
21 January 2020
17 November 2022

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment80
Start date8 April 2015
Primary completion21 January 2020
Estimated completion17 November 2022
Sites23 locations across France, Italy, Japan, Belgium, Austria, Germany, Norway, Canada

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Under 25, any sex, with B-cell Acute Lymphoblastic Leukemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Overall Remission Rate (ORR) as Determined by Independent Review Committee (IRC) Assessment. Primary · during the 3 months after tisagenlecleucel administration

Evaluating the efficacy of tisagenlecleucel therapy from all manufacturing facilities as measured by overall remission rate (ORR) during the 3 months after tisagenlecleucel administration. ORR included complete response (CR) and CR with incomplete blood count recovery (CRi) as determined by an Independent Review Committee assessment. Per response criteria defined by National Comprehensive Cancer Network (NCCN), American Society of Hematology (ASH) and International Working Group (IWG) guidelines. CR is defined as: Bone marrow \<5% blasts, Peripheral blood: Neutrophils \>1.0 x 10\^9/L, and Pl

GroupValue95% CI
Main Cohort: Single Dose of CTL01982.372.1 – 90.0
Cohort 1: Single Dose of CTL019100.0NA – NA
Percentage of Participants With Overall Remission Rate (ORR) as Per IRC From US Manufacturing Facilities in the Main Cohort Only (Key Secondary) Secondary · 3 months after tisagenlecleucel administration

These are the percentage of participants with ORR who achieved overall remission rate which includes complete response (CR) and CR with incomplete blood count recovery (CRi) as determined by IRC assessment after having been infused with tisagenlecleucel from US manufacturing facilities.

GroupValue95% CI
Main Cohort: Single Dose of CTL01982.170.8 – 90.4
Percentage of Participants With Best Overall Response (BOR) of CR or CRi With Minimal Residue Disease (MRD) Negative Bone Marrow From US Manufacturing Facility as Per IRC in the Main Cohort Only (Key Secondary) Secondary · 3 months after tisagenlecleucel administration

These are the percentage of participants who achieved Best Overall Response (BOR) of complete response (CR) or complete response with incomplete blood count recovery (CRi) with an MRD-negative bone marrow by central analysis using flow cytometry among participants who received tisagenlecleucel from US manufacturing facilities only, by IRC assessment.

GroupValue95% CI
Main Cohort: Single Dose of CTL01982.170.8 – 90.4
Percentage of Participants With Best Overall Response (BOR) of CR or CRi With MRD Negative Bone Marrow by Flow Cytometry From All Manufacturing Facilities as Per IRC in the Main Cohort Only (Key Secondary) Secondary · 3 months after tisagenlecleucel administration

These are the percentage of participants who achieved Best Overall Response (BOR) of CR or CRi with an MRD-negative bone marrow by central analysis using flow cytometry among participants who received tisagenlecleucel from all manufacturing facilities by IRC assessment. MRD negative = MRD% \< 0.01%

GroupValue95% CI
Main Cohort: Single Dose of CTL01981.070.6 – 89.0
Percentage of Participants Who Achieved CR or CRi Without Hematopoietic Stem Cell Transplantation (HSCT) Secondary · 6 months after tisagenlecleucel administration

These are the participants who achieved CR or CRi without HSCT between tisagenlecleucel (CTL019) infusion and Month 6 response assessment.

GroupValue95% CI
Main Cohort: Single Dose of CTL01960.849.1 – 71.6
Cohort 1: Single Dose of CTL019100.0NA – NA
Percentage of Participants Who Achieved CR or CRi and Then Proceeded to Hematopoietic Stem Cell Transplantation (HSCT) While in Remission Prior to Month 6 Resoonse Secondary · 6 months

These are the participants who achieved CR or CRi and then proceeded to HSCT while in remission prior to Month 6 response assessment

GroupValue95% CI
Main Cohort: Single Dose of CTL0197.62.8 – 15.8
Cohort 1: Single Dose of CTL0190.0NA – NA
Number of Participants Who Proceeded to Hematopoietic Stem Cell Transplantation (HSCT) After Tisagenlecleucel (CTL019) Infusion Secondary · up to 6 months

These are the participants who achieved CR or CRi and then proceeded to SCT after being infused by tisagenlecleucel.

GroupValue95% CI
Main Cohort: Single Dose of CTL01918
Cohort 1: Single Dose of CTL0190
Duration of Remission (DOR) Secondary · 60 months

DOR is the time from achievement of CR or CRi at any time post-infusion, whichever occurs first, to relapse or death.

GroupValue95% CI
Main Cohort: Single Dose of CTL01946.817.8 – NA
Cohort 1: Single Dose of CTL019NANA – NA
Site of Involvement of Subsequent Relapse Secondary · 60 months

Anatomical location of relapse in participants who achieved prior CR/CRi subsequent to tisagenlecleucel infusion.

BM and/or blood relapse
GroupValue95% CI
Main Cohort: Single Dose of CTL01923
Extramedullary only
GroupValue95% CI
Main Cohort: Single Dose of CTL0192
Unknown
GroupValue95% CI
Main Cohort: Single Dose of CTL0194
Relapse-free Survival Per IRC Assessment Secondary · 60 months

RFS is the time from achievement of CR or CRi at any time post-infusion, whichever occurs first, to relapse or death due to any cause during CR or CRi.

GroupValue95% CI
Main Cohort: Single Dose of CTL01946.817.8 – NA
Cohort 1: Single Dose of CTL019NANA – NA
Event-free Survival Per IRC Assessment Secondary · 60 months

EFS is the time from date of tisagenlecleucel infusion to the earliest of death, relapse or treatment failure.

GroupValue95% CI
Main Cohort: Single Dose of CTL01923.79.2 – NA
Cohort 1: Single Dose of CTL019NANA – NA
Overall Survival (OS) Secondary · 60 months

OS, is the time from date of tisagenlecleucel infusion to the date of death due to any reason.

GroupValue95% CI
Main Cohort: Single Dose of CTL019NA45.6 – NA
Cohort 1: Single Dose of CTL019NANA – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: 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 60 months for each patient. Deaths were collected at all points post-treatment (including post-treatment survival follow-up period) until the patient completed the study duration (60 months) or further safety follow-up under the study protocol. Therefore on-treatment deaths include post-treatment survival follow-up deaths.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Main Cohort (On-treatment + Post-treatment Survival Follow-up Deaths)
Serious: 63/79 (80%)
Deaths: 33/79
Cohort 1 (On-treatment + Post-treatment Survival Follow-up Deaths)
Serious: 0/1 (0%)
Deaths: 0/1

Serious adverse events (123 terms)

ReactionSystemMain Cohort (On-treatment …Cohort 1 (On-treatment + P…
Cytokine release syndromeImmune system disorders
Febrile neutropeniaBlood and lymphatic system disorders
HypotensionVascular disorders
PyrexiaGeneral disorders
Acute kidney injuryRenal and urinary disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Disseminated intravascular coagulationBlood and lymphatic system disorders
Cardiac arrestCardiac disorders
Multiple organ dysfunction syndromeGeneral disorders
SepsisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Back painMusculoskeletal and connective tissue disorders
Cardiac failureCardiac disorders
DiarrhoeaGastrointestinal disorders
PancreatitisGastrointestinal disorders
Haemophagocytic lymphohistiocytosisImmune system disorders
Candida infectionInfections and infestations
EncephalitisInfections and infestations
Encephalitis viralInfections and infestations
GastroenteritisInfections and infestations
Herpes zosterInfections and infestations
PneumoniaInfections and infestations
Respiratory syncytial virus infectionInfections and infestations
Rhinovirus infectionInfections and infestations
Other adverse events (110 terms — click to expand)

ReactionSystemMain Cohort (On-treatment …Cohort 1 (On-treatment + P…
Cytokine release syndromeImmune system disorders
HypogammaglobulinaemiaImmune system disorders
PyrexiaGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
HeadacheNervous system disorders
AnaemiaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
White blood cell count decreasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
HypokalaemiaMetabolism and nutrition disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
HypophosphataemiaMetabolism and nutrition disorders
HypotensionVascular disorders
TachycardiaCardiac disorders
FatigueGeneral disorders
Lymphocyte count decreasedInvestigations
Pain in extremityMusculoskeletal and connective tissue disorders
HypocalcaemiaMetabolism and nutrition disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
AnxietyPsychiatric disorders
Febrile neutropeniaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations
Blood bilirubin increasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
NeutropeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
HypoalbuminaemiaMetabolism and nutrition disorders
Pulmonary oedemaRespiratory, thoracic and mediastinal disorders
MyalgiaMusculoskeletal and connective tissue disorders
International normalised ratio increasedInvestigations
HyperglycaemiaMetabolism and nutrition disorders
HyperuricaemiaMetabolism and nutrition disorders
Acute kidney injuryRenal and urinary disorders

Most-reported serious reactions: Cytokine release syndrome, Febrile neutropenia, Hypotension, Pyrexia, Acute kidney injury, Hypoxia, Respiratory failure, Disseminated intravascular coagulation.

Data from ClinicalTrials.gov NCT02435849 adverse events section.

Sponsor's own description

This is a single arm, open-label, multi-center, phase II study to determine the efficacy and safety of CTL019 in pediatric patients with r/r B-cell ALL.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia.
    Maude SL, Laetsch TW, Buechner J, Rives S, et al · · 2018 · cited 4269× · PMID 29385370 · DOI 10.1056/nejmoa1709866
  2. Engineered T cells: the promise and challenges of cancer immunotherapy.
    Fesnak AD, June CH, Levine BL. · · 2016 · cited 812× · PMID 27550819 · DOI 10.1038/nrc.2016.97
  3. Recent advances and discoveries in the mechanisms and functions of CAR T cells.
    Larson RC, Maus MV. · · 2021 · cited 644× · PMID 33483715 · DOI 10.1038/s41568-020-00323-z
  4. Global Manufacturing of CAR T Cell Therapy.
    Levine BL, Miskin J, Wonnacott K, Keir C. · · 2017 · cited 485× · PMID 28344995 · DOI 10.1016/j.omtm.2016.12.006
  5. Clinical development of CAR T cells-challenges and opportunities in translating innovative treatment concepts.
    Hartmann J, Schüßler-Lenz M, Bondanza A, Buchholz CJ. · · 2017 · cited 353× · PMID 28765140 · DOI 10.15252/emmm.201607485
  6. Exploratory trial of a biepitopic CAR T-targeting B cell maturation antigen in relapsed/refractory multiple myeloma.
    Xu J, Chen LJ, Yang SS, Sun Y, et al · · 2019 · cited 309× · PMID 30988175 · DOI 10.1073/pnas.1819745116
  7. Three-Year Update of Tisagenlecleucel in Pediatric and Young Adult Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia in the ELIANA Trial.
    Laetsch TW, Maude SL, Rives S, Hiramatsu H, et al · · 2023 · cited 282× · PMID 36399695 · DOI 10.1200/jco.22.00642
  8. Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel.
    Porter D, Frey N, Wood PA, Weng Y, et al · · 2018 · cited 266× · PMID 29499750 · DOI 10.1186/s13045-018-0571-y

Verify or expand the search:

Other trials of CTL019

Trials testing the same drug.

Other recruiting trials for B-cell Acute Lymphoblastic Leukemia

Currently open trials in the same condition.

Other Novartis Pharmaceuticals trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing