Trial Outcomes & Findings for A Study to Evaluate the Safety and Efficacy of JCAR017 in Pediatric Subjects With Relapsed/Refractory (r/r) B-cell Acute Lymphoblastic Leukemia (B-ALL) and B-cell Non-Hodgkin Lymphoma (B-NHL) (NCT NCT03743246)

The study was terminated and hence participants were not enrolled in Phase 2 cohorts (r/r B-ALL; MRD+ B-ALL; r/r B-NHL).

A Study to Evaluate the Safety and Efficacy of JCAR017 in Pediatric Subjects With Relapsed/Refractory (r/r) B-cell Acute Lymphoblastic Leukemia (B-ALL) and B-cell Non-Hodgkin Lymphoma (B-NHL)

An AE is defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 30 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater.

A DLT was defined as: * Death not related to disease progression * Grade (Gr) 4 (Life-threatening) neurotoxicity * Gr 3 (Severe) neurotoxicity of greater than 7 days * Gr 3 neurotoxicity does not revert to baseline within 28 days of the start date of the Grade 3 event * Seizures of grade that do not resolve within 7 days * Gr 4 cytokine release syndrome (CRS) that does not resolve to Grade ≤ 3 within 3 days * Gr 3 CRS that does not resolve to Grade ≤ 2 within 7 days * Any increase in aspartate aminotransferase (AST) or ALT \> 3 × ULN and concurrent increase in total bilirubin \> 2 × ULN that is unrelated to CRS and has no other probable reason to explain the combination of increases * Any cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic Gr 3 or 4 event not pre-existing or not due to the underlying malignancy * Any other Gr 3 or 4 event deemed unexpected by the Investigator and considered a DLT upon evaluation by the safety review committee

Concentration of JCAR017 in Peripheral Blood was assessed by droplet digital polymerase chain reaction.

An AE is defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 90 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater. The following scale for grading was used - Grade 3 = Severe, Grade 4 = Life-Threatening.

Serious adverse events (SAE) are defined as any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/ birth defect; constitutes an important medical event. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 90 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater.

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.

Successful product was defined as JCAR017 product was generated and able to be QC released (including nonconforming product) for infusion. Unsuccessful product is defined as no JCAR017 product could be generated after two manufacturing attempts using a single apheresis product for starting material or product was unable to be QC released for infusion.

ORR is defined as the percentage of participants who achieved either a complete response (CR) or complete response with incomplete blood recovery (CRi) on Day 28 that is confirmed on Day 56. Response assessment was performed according to the 2019 Comprehensive Cancer Network (NCCN) response criteria guidelines for pediatric acute lymphoblastic leukemia (ALL). CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets \< 100,000/μL or ANC is \< 1000/μL.

DOR is defined as time from first response (either CR or CRi) until progressive disease (PD), disease relapse, or death from any cause, whichever occurs first. Response assessment was performed according to the 2019 Comprehensive Cancer Network (NCCN) response criteria guidelines for pediatric ALL. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets \< 100,000/μL or ANC is \< 1000/μL. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease.

RFS is defined as time from conforming JCAR017 infusion to the first progressive disease (PD), relapsed disease or death from any cause, whichever occurs first. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. Relapsed disease is defined as Reappearance of blasts in the blood or bone marrow (\> 5%) or \> 1% with previous/supportive molecular findings or in any extramedullary site after a CR. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks.

EFS is defined as time from conforming JCAR017 infusion to progressive disease (PD), relapsed disease, start of a new anticancer therapy including HSCT or death from any cause, whichever occurs first. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. Relapsed disease is defined as Reappearance of blasts in the blood or bone marrow (\> 5%) or \> 1% with previous/supportive molecular findings or in any extramedullary site after a CR. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. Only responders are included in he analysis. Censored participants were also analyzed.

OS is defined as the interval from the date of first confirming JCAR017 infusion to the date of death due to any reason.

Minimal Residual Disease (MRD) Negative Response Rate is defined as the percentage of participants achieving either a CR or CRi with a MRD negative bone marrow on Day 28, confirmed on Day 56. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets \< 100,000/μL or ANC is \< 1000/μL. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. Disease assessments recorded on or after start of a new anticancer therapy, including HSCT, will not be considered, nor will disease assessments reported after a PD or relapse has been observed.

Number of participants who undergo HSCT after receiving a JCAR017 infusion and achieving a response are presented. The time of proceeding to HSCT is defined as the time of commencing the conditioning regimen as required for HSCT. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets \< 100,000/μL or ANC is \< 1000/μL. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease.