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)

This is a Phase 1b/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 1b, twenty r/r B-ALL pediatric (< 18 years of age) subjects will be treated. The
first 10 pediatric subjects will be treated at a target dose of 0.5x10^6 JCAR017 CAR+ T
cells/kg, with a maximum dose of 0.5x10^8 JCAR017 CAR+ T cells (non-weight adjusted). If this
dose is confirmed to be safe and tolerable, an additional 10 pediatric subjects will be
treated at a target dose of 1x10^6 JCAR017 CAR+ T cells/kg, with a maximum dose of 1.0x10^8
JCAR017 CAR+ T cells (non-weight adjusted). The highest dose tested with no more than 2
subjects experiencing a dose-limiting toxicity (DLT) will be declared the RP2D that will be
applied in Phase 2. 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.

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.

- Cohort 1 (r/r B-ALL): 38 evaluable pediatric subjects. The 10 pediatric subjects treated
at the RP2D in Phase 1b will be included in, and form part of, the sample size of Phase
2, totaling 48 evaluable pediatric subjects in Cohort 1 (13 subjects in Stage 1 and 35
in Stage 2)

- 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 subjects between 18 and 25 years of age will 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.

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

1. Phase 1b: Subject < 18 years of age and weighs ≥ 12 kg (for subjects receiving a dose
of 0.5x10^6 JCAR017 CAR+ T cells/kg) or ≥ 6 kg (for subjects receiving a dose of
1x10^6 JCAR017 CAR+ T cells/kg) at the time of signing the informed consent form
(ICF)/informed assent form (IAF). Phase 2: Subject ≤ 25 years of age and weighs ≥ 12
kg (if RP2D is 0.5 x 10^6 JCAR017 CAR+ T cells/kg) or ≥ 6 kg (if RP2D is 1 x 10^6
JCAR017 CAR+ T cells/kg) at the time of signing the ICF/IAF.

2. Subject (when applicable, parental/legal representative) must understand and
voluntarily provide permission to the ICF/IAF prior to conducting any study-related
assessments/procedures.

3. Subject is willing and able to adhere to the study visit schedule and other protocol
requirements.

4. Investigator considers the subject is appropriate for adoptive T cell therapy.

5. Evidence of CD19 expression via flow cytometry (peripheral blood or bone marrow) or
immunohistochemistry (bone marrow biopsy)

6. Subject has a Karnofsky score of ≥ 50 (subjects ≥ 16 years of age) or a Lansky score ≥
50 (subjects < 16 years of age).

7. Phase 1b: Subjects with r/r B-ALL, defined as morphological evidence of disease in BM
(5% or greater lymphoblast by morphology) and either of the following:

- First or greater marrow relapse, or

- Any marrow relapse after allogeneic HSCT, or

- Primary refractory defined as not achieving a CR or a CRi after 2 or more
separate induction regimens (or chemo-refractory as not achieving CR/CRi after 1
cycle of standard chemotherapy for relapsed leukemia), or

- Ineligible for allogeneic HSCT

Phase 2: Subjects with one of the following:

- Cohort 1: r/r B-ALL, defined as morphological evidence of disease in BM (5% or
greater lymphoblast by morphology) and either:

- First or greater marrow relapse, or

- Any marrow relapse after allogeneic HSCT, or

- Primary refractory defined as not achieving a CR or a CRi after 2 or more
separate induction regimens (or chemo-refractory as not achieving CR/CRi
after 1 cycle of standard chemotherapy for relapsed leukemia), or

- Ineligible for allogeneic HSCT.

- Cohort 2: MRD+ B-ALL, defined as:

- < 5% lymphoblasts by morphology

- MRD detected by a validated assay at a frequency of 1 x10-4 or greater in BM
cells after two lines of therapy.

- Cohort 3: r/r B-NHL, defined as measurable disease after 1 or more lines of
chemotherapy and/or having failed HSCT or being ineligible for HSCT.

8. Subjects with Philadelphia chromosome positive ALL are eligible if they are intolerant
to or have failed one or more lines of tyrosine-kinase inhibitor (TKI) therapy or if
TKI therapy is contraindicated.

9. Adequate organ function, defined as:

- Adequate BM function to receive LD chemotherapy as assessed by the Investigator.

- Subject with adequate renal function, which is defined as:

Creatinine clearance calculated using the Schwartz formula, or radioisotope glomerular
filtration rate (GFR) > 70 mL/min/1.73 m2.

- Adequate pulmonary function, defined as ≤ Grade 1 dyspnea according to Common
Toxicity Criteria for Adverse Events (CTCAE) and oxygen saturation (SaO2) ≥ 92%
on room air.

- Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) ≥
40% as assessed by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA)
within 4 weeks prior to leukapheresis.

10. Adequate vascular access for leukapheresis procedure.

11. Participants must agree to use effective contraception

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

1. Subject has any significant medical condition, laboratory abnormality, or psychiatric
illness that would prevent the subject from participating in the study.

2. Subject has any condition including the presence of laboratory abnormalities, which
places the subject at unacceptable risk if he/she were to participate in the study.

3. Subject has any condition that confounds the ability to interpret data from the study.

4. Subject with a history of another primary malignancy that has not been in remission
for at least 2 years prior to enrollment.

5. Subjects who have received previous CD19-targeted therapy must have CD19-positive
disease confirmed since completing the prior CD19-targeted therapy.

6. Prior CAR T cell or other genetically-modified T cell therapy.

7. Subject with a previous history of or active hepatitis B, hepatitis C, or human
immunodeficiency virus (HIV) infection.

8. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection
(including tuberculosis) despite appropriate antibiotics or other treatment at the
time of leukapheresis or JCAR017 infusion.

9. Subject has presence of acute or chronic graft-versus-host disease (GVHD).

10. Subject with active autoimmune disease requiring immunosuppressive therapy.

11. Subject has cardiac disorders (CTCAE version 4.03 Grade 3 or 4) within the past 6
months.

12. Subject with a concomitant genetic syndrome, with the exception of Down's syndrome.

13. Subject with active CNS disease and significant neurological deterioration. Subjects
with CNS-2 or CNS-3 involvement are eligible provided they are asymptomatic and do not
have significant neurological deterioration and, in the opinion of the study
investigator.

14. Subject with a history or presence of clinically relevant CNS pathology.

15. Subject is pregnant or nursing.

16. Subject has used the following:

- Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or
equivalent) within 7 days prior to leukapheresis or 72 hours prior to JCAR017
infusion. Physiologic replacement, topical, and inhaled steroids are permitted.

- Low-dose chemotherapy (eg, vincristine, rituximab, cyclophosphamide ≤ 300 mg/m2)
given after leukapheresis to maintain disease control must be stopped ≥ 7 days
prior to LD chemotherapy.

- Cytotoxic chemotherapeutic agents that are not considered lymphotoxic (see below)
within 1 week prior to leukapheresis. Oral anticancer agents, including
lenalidomide and ibrutinib, are allowed if at least 3 half-lives have elapsed
prior to leukapheresis.

- Lymphotoxic chemotherapeutic agents (eg, cyclophosphamide, ifosfamide,
bendamustine) within 2 weeks prior to leukapheresis.

- Experimental agents within 4 weeks prior to leukapheresis unless no response or
PD is documented on the experimental therapy and at least 3 half-lives have
elapsed prior to leukapheresis.

- Immunosuppressive therapies within 4 weeks prior to leukapheresis and JCAR017
infusion (eg, calcineurin inhibitors, methotrexate or other chemotherapeutics,
mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as
antitumor necrosis factor [TNF], anti-IL-6, or anti-IL-6R).

- Donor lymphocyte infusions (DLI) within 6 weeks prior to JCAR017 infusion.

- Radiation within 6 weeks prior to leukapheresis. Subjects must have PD in
irradiated lesions or have additional non-irradiated lesions to be eligible.
Radiation to a single lesion, if additional non-irradiated, measurable lesions
are present, is allowed up to 2 weeks prior to leukapheresis.

- Allogeneic HSCT within 90 days prior to leukapheresis.

17. Tumor invasion of venous or arterial vessels (B-NHL subjects only).

18. Deep Venous Thrombosis (DVT)/Pulmonary Embolism (PE) within 3 months of ICF signature
and/or DVT/PE that requires ongoing therapeutic levels of anti-coagulation.