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NCT03610724: BIANCA

Phase II Open Label Trial to Determine Safety & Efficacy of Tisagenlecleucel in Pediatric Non-Hodgkin Lymphoma Patients

Completed Phase 2 Results posted Last updated 20 June 2024
What this trial tests

Phase 2 trial testing Tisagenlecleucel in Non-Hodgkin Lymphoma in 34 participants. Completed in 26 April 2023.

Timeline
15 February 2019
Primary endpoint
27 July 2021
26 April 2023

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment34
Start date15 February 2019
Primary completion27 July 2021
Estimated completion26 April 2023
Sites26 locations across Denmark, France, Finland, Italy, Japan, Netherlands, Austria, United Kingdom

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Under 25, any sex, with Non-Hodgkin Lymphoma. 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.

Overall Response Rate (ORR) as Determined by Local Investigator Primary · 6 months post-tisagenlecleucel infusion

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.

GroupValue95% CI
Tisagenlecleucel32.115.9 – 52.4
Duration of Response (DOR) Secondary · Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48

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.

GroupValue95% CI
TisagenlecleucelNA1.0 – NA
Event Free Survival (EFS) Secondary · Post-infusion Day 28, Month 3, Month 6, Month 9, Month 12, Month 18, Month 24, and then annually until Month 48

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).

GroupValue95% CI
Tisagenlecleucel2.11.1 – 2.8
Relapse Free Survival (RFS) Secondary · 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) 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.

GroupValue95% CI
TisagenlecleucelNA1.0 – NA
Progression Free Survival (PFS) Secondary · 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) 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

GroupValue95% CI
Tisagenlecleucel2.51.1 – 2.9
Overall Survival (OS) Secondary · 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) is defined as the time from date of first tisagenlecleucel infusion to the date of death due to any cause.

GroupValue95% CI
Tisagenlecleucel10.43.4 – NA
Cellular Kinetics Parameter: Cmax Secondary · 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

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.

GroupValue95% CI
Tisagenlecleucel5140± 238.9
Cellular Kinetics Parameter: Tmax Secondary · 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

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.

GroupValue95% CI
Tisagenlecleucel12.71.90 – 21.9
Cellular Kinetics Parameter: AUC0-28d Secondary · 0 to 28 days

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.

GroupValue95% CI
Tisagenlecleucel53500± 154.9
Cellular Kinetics Parameter: Clast Secondary · 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

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.

GroupValue95% CI
Tisagenlecleucel344± 350.4
Cellular Kinetics Parameter: Tlast Secondary · 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

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.

GroupValue95% CI
Tisagenlecleucel40.013.0 – 1090
Levels of Pre-existing and Treatment Induced Humoral Immunogenicity and Cellular Immunogenicity Against Tisagenlecleucel Cellular Kinetics, Safety and Efficacy Secondary · Until disease progression or through study completion, up to 4 years

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

anti-tisagenlecleucel antibodies (positive) at baseline (BL)
GroupValue95% CI
Tisagenlecleucel87.9
anti-tisagenlecleucel antibodies (positive) anytime post-BL
GroupValue95% CI
Tisagenlecleucel97.0

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 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). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Tisagenlecleucel - Post-infusion
Serious: 24/33 (73%)
Deaths: 17/33
Tisagenlecleucel - Pre-infusion Deaths
Serious: 0
Deaths: 1/34

Serious adverse events (38 terms)

ReactionSystemTisagenlecleucel - Post-in…Tisagenlecleucel - Pre-inf…
Cytokine release syndromeImmune system disorders
PyrexiaGeneral disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
Depressed level of consciousnessNervous system disorders
Peripheral sensorimotor neuropathyNervous system disorders
SeizureNervous system disorders
Acute kidney injuryRenal and urinary disorders
Cardiac arrestCardiac disorders
TachycardiaCardiac disorders
Vision blurredEye disorders
Dental cariesGastrointestinal disorders
Large intestinal obstructionGastrointestinal disorders
PancreatitisGastrointestinal disorders
ProctitisGastrointestinal disorders
Chest painGeneral disorders
Condition aggravatedGeneral disorders
Disease progressionGeneral disorders
Haemophagocytic lymphohistiocytosisImmune system disorders
Aspergillus infectionInfections and infestations
Candida infectionInfections and infestations
Pseudomonas infectionInfections and infestations
SepsisInfections and infestations
Urinary tract infectionInfections and infestations
Other adverse events (75 terms — click to expand)

ReactionSystemTisagenlecleucel - Post-in…Tisagenlecleucel - Pre-inf…
Cytokine release syndromeImmune system disorders
PyrexiaGeneral disorders
VomitingGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
Neutrophil count decreasedInvestigations
NauseaGastrointestinal disorders
Platelet count decreasedInvestigations
White blood cell count decreasedInvestigations
HeadacheNervous system disorders
NeutropeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
LeukopeniaBlood and lymphatic system disorders
StomatitisGastrointestinal disorders
FatigueGeneral disorders
Alanine aminotransferase increasedInvestigations
Blood creatinine increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
TachycardiaCardiac disorders
ChillsGeneral disorders
HypomagnesaemiaMetabolism and nutrition disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Sinus tachycardiaCardiac disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Catheter site painGeneral disorders
HypogammaglobulinaemiaImmune system disorders
Infusion related reactionInjury, poisoning and procedural complications
Blood lactate dehydrogenase increasedInvestigations
Lymphocyte count decreasedInvestigations
Weight decreasedInvestigations
HyperphosphataemiaMetabolism and nutrition disorders
ParaesthesiaNervous system disorders
PruritusSkin and subcutaneous tissue disorders
HypertensionVascular disorders
Bone marrow failureBlood and lymphatic system disorders
CoagulopathyBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders

Most-reported serious reactions: Cytokine release syndrome, Pyrexia, Pleural effusion, Febrile neutropenia, Abdominal pain, Depressed level of consciousness, Peripheral sensorimotor neuropathy, Seizure.

Data from ClinicalTrials.gov NCT03610724 adverse events section.

Sponsor's own description

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.

Publications & conference data

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

  1. Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials.
    Westin JR, Kersten MJ, Salles G, Abramson JS, et al · · 2021 · cited 163× · PMID 34310745 · DOI 10.1002/ajh.26301
  2. CAR-T cell therapy for cancer: current challenges and future directions.
    Zugasti I, Espinosa-Aroca L, Fidyt K, Mulens-Arias V, et al · · 2025 · cited 81× · PMID 40610404 · DOI 10.1038/s41392-025-02269-w
  3. State of the art in CAR T cell therapy for CD19+ B cell malignancies.
    Frigault MJ, Maus MV. · · 2020 · cited 77× · PMID 32235098 · DOI 10.1172/jci129208
  4. CAR T-cell product performance in haematological malignancies before and after marketing authorisation.
    Elsallab M, Levine BL, Wayne AS, Abou-El-Enein M. · · 2020 · cited 65× · PMID 32007196 · DOI 10.1016/s1470-2045(19)30729-6
  5. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma.
    Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, et al · · 2021 · cited 36× · PMID 34515338 · DOI 10.1002/14651858.cd013365.pub2
  6. CD19-Targeted Immunotherapies for Diffuse Large B-Cell Lymphoma.
    Gambella M, Carlomagno S, Raiola AM, Giannoni L, et al · · 2022 · cited 21× · PMID 35280988 · DOI 10.3389/fimmu.2022.837457
  7. Children's Oncology Group's 2023 blueprint for research: Non-Hodgkin lymphoma.
    El-Mallawany NK, Alexander S, Fluchel M, Hayashi RJ, et al · · 2023 · cited 11× · PMID 37449925 · DOI 10.1002/pbc.30565
  8. Refractory Burkitt Lymphoma: Diagnosis and Interventional Strategies.
    Malfona F, Testi AM, Chiaretti S, Moleti ML. · · 2024 · cited 10× · PMID 38510818 · DOI 10.2147/blctt.s407804

Verify or expand the search:

Other trials of Tisagenlecleucel

Trials testing the same drug.

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Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03610724.

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