This is a Phase 1/2, open-label, single arm, multicohort study to evaluate the safety and
efficacy of JCAR017 in pediatric subjects aged 25 years with CD19+ r/r B-ALL and B-NHL.
Phase 1 will identify a recommended Phase 2 dose (RP2D). Phase 2 will evaluate the efficacy
of JCAR017 RP2D in the following three disease cohorts: Cohort 1 (r/r B-ALL), Cohort 2 (MRD+
B-ALL) and Cohort 3 (r/r B-NHL, [DLBCL, BL, or PMBCL]). A Simon's Optimal two-stage study
design will be applied to Cohort 1 and 2 in Phase 2.
This is a Phase 1/2, open-label, single arm, multicohort study incorporating Simon's Optimal
two-stage design to evaluate the safety and efficacy of JCAR017 in pediatric subjects aged
25 years with CD19+ r/r B-ALL and B-NHL.
In the Phase 1, up to 5 dose levels will be of JCAR017 will be evaluated. Enrollment will
commence in pediatric subjects with r/r B-ALL at Dose Level 1 (DL1) of 0.05x10^6 CAR+ T
cells/kg (maximum DL1 of 5x10^6 JCAR017 CAR+ T cells [non-weight adjusted]). If this dose is
confirmed to be safe and tolerable, additional subjects will be enrolled at higher dose(s) up
to 0.75 x10^6 CAR+ T cells/kg (maximum of 75x10^6 JCAR017 CAR+ T cells [non-weight adjusted])
with the aim to identify the RP2D. Dose escalation/de-escalation will follow a modified
toxicity probability interval (mTPI-2) algorithm. A Safety Review Committee (SRC) will
recommend the Phase 2 dose (defined as RP2D) based on an integrated assessment of the safety,
PK and preliminary efficacy information from at least 10 pediatric subjects treated at the
In Phase 2, a minimum of 71 additional subjects (< 18 years of age) will be enrolled into one
of the 3 cohorts listed below. The sample size for Cohorts 1 and 2 is calculated according to
Simon's Optimal two-stage design. The 10 or more pediatric subjects treated at the RP2D in
Phase 1 will form part of the sample size (ie, Cohort 1 and Cohort 2). Therefore, the
protocol intends to treat 81 primary endpoint evaluable pediatric subjects in Phase 2, if
warranted by the evaluation of results at the completion of the first stage of the study in
Cohort 1 (r/r B-ALL): 48 evaluable pediatric subjects (13 subjects in Stage 1 and 35 in
Cohort 2 (MRD+ B-ALL): 23 evaluable pediatric subjects (9 subjects in Stage 1 and 14
subjects in Stage 2)
Cohort 3 (r/r B-NHL [DLBCL, BL, or PMBCL]): 10 evaluable pediatric subjects. Due to the
very low incidence rate and therefore expected low subject accrual, there is no formal
sample size for this arm.
Up to 20 additional B-ALL subjects between 18 and 25 years of age may be enrolled in Phase 2.
Following treatment with JCAR017 subjects will then enter the post-treatment period for
disease progression/relapse, safety, CAR T cell persistence, and survival up to 24 months
after administration of JCAR017.
Efficacy will be assessed both locally and by an Independent Review Committee. Response
assessments will be based on bone marrow and blood morphologic criteria, physical examination
findings, along with laboratory assessments of cerebral spinal fluid (CSF) and bone marrow
MRD (B-ALL only) assessments. B-NHL subjects will also have radiographic disease assessment
by CT/MRI scans and tumor biopsies, if accessible.
Post-study follow-up for survival, relapse, long-term toxicity, and lentiviral vector safety
will continue under a separate long-term follow-up protocol for up to 15 years after the
JCAR017 infusion as per health authority regulatory guidelines.
An Independent Data Monitoring Committee will monitor the study conduct.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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