Determine Efficacy and Safety of CTL019 in Pediatric Patients With Relapsed and Refractory B-cell ALL

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. The study will have the following
sequential phases: Screening, Pre-Treatment (Cell Product Preparation & Lymphodepleting
Chemotherapy), Treatment and Primary Follow-up, Secondary Follow-up (if applicable) and
Survival Follow-up. The total duration of the study is 5 years from CTL019 cell infusion.

Inclusion Criteria:

- Relapsed or refractory pediatric B-cell ALL.

1. 2nd or greater Bone Marrow (BM) relapse OR.

2. Any BM relapse after allogeneic stem cell transplantation (SCT) and must be ≥ 6
months from SCT at the time of CTL019 infusion OR.

3. Primary refractory as defined by not achieving a CR after 2 cycles of a standard
chemotherapy regimen or chemorefractory as defined by not achieving a CR after 1
cycle of standard chemotherapy for relapsed leukemia OR.

4. Patients with Philadelphia chromosome positive (Ph+) ALL are eligible if they are
intolerant to or have failed 2 lines of tyrosine kinase inhibitor therapy (TKI),
or if TKI therapy is contraindicated OR.

5. Ineligible for allogeneic SCT.

- For relapsed patients, documentation of CD19 tumor expression demonstrated in bone
marrow or peripheral blood by flow cytometry within 3 months of study entry.

- Adequate organ function defined as:

1. Renal function defined as:

A serum creatinine based on age/gender as follows:

Maximum Serum Creatinine (mg/dL). Age Male Female

1 to < 2 years 0.6 0.6 2 to < 6 years 0.8 0.8 6 to < 10 years 1.0 1.0 10 to < 13
years 1.2 1.2 13 to < 16 years 1.5 1.4

≥ 16 years 1.7 1.4.

2. Alanine Aminotransferase (ALT) ≤ 5 times the upper limit of normal (ULN) for age.

3. Bilirubin < 2.0 mg/dL.

4. Must have a minimum level of pulmonary reserve as ≤ Grade 1 dyspnea and pulse
oxygenation > 91% on room air.

5. Left Ventricular Shortening Fraction (LVSF) ≥ 28% confirmed by echocardiogram
(ECHO), or Left Ventricular Ejection Fraction (LVEF) ≥ 45% confirmed by
echocardiogram or Multiple Uptake Gated Acquisition (MUGA).

- Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening.

- Life expectancy > 12 weeks.

- Age 3 at the time of screening to age 21 at the time of initial diagnosis

- Karnofsky (age ≥ 16 years) or Lansky (age < 16 years) performance status ≥ 50 at
screening.

- Must have an apheresis product of non-mobilized cells received and accepted by the
manufacturing site.

Exclusion Criteria:

- Isolated extra-medullary disease relapse

- Patients with concomitant genetic syndrome: such as patients with Fanconi anemia,
Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome.
Patients with Down Syndrome will not be excluded.

- Patients with Burkitt's lymphoma/leukemia (i.e. patients with mature B-cell ALL,
leukemia with B-cell [sIg positive and kappa or lambda restricted positivity] ALL,
with FAB L3 morphology and /or a MYC translocation)

- Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative
intent and with no evidence of active disease

- Treatment with any prior gene therapy product

- Has had treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19
therapy

- Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening),
or any uncontrolled infection at screening

- Human Immunodeficiency Virus (HIV) positive test within 8 weeks of screening

- Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD).

- Active CNS involvement by malignancy, defined by CNS-3 per NCCN guidelines.

- Patient has an investigational medicinal product within the last 30 days prior to
screening.

- Pregnant or nursing women.

- Women of child-bearing potential (defined as all women physiologically capable of
becoming pregnant) and all male participants, unless they are using highly effective
methods of contraception for a period of 1 year after the CTL019 infusion.

- The following medications are excluded:

1. Steroids: Therapeutic doses of steroids must be stopped > 72 hours prior to
CTL019 infusion. However, the following physiological replacement doses of
steroids are allowed:

< 12 mg/m2/day hydrocortisone or equivalent

2. Allogeneic cellular therapy: Any donor lymphocyte infusions (DLI) must be
completed > 6 weeks prior to CTL019 infusion

3. GVHD therapies: Any drug used for GVHD must be stopped > 4 weeks prior to CTL019
infusion (e.g. calcineurin inhibitors, methotrexate or other chemotherapy drugs,
mycophenolyate, rapamycin, thalidomide, or immunosuppressive antibodies such as
anti-CD20 (rituximab), anti-TNF, anti-IL6 or anti-IL6R)

4. Chemotherapy:

The following drugs must be stopped > 1 week prior to CTL019 infusion and should
not be administered concomitantly or following lymphodepleting chemotherapy:
hydroxyurea, vincristine, 6-mercaptopurine, 6-thioguanine, methotrexate < 25
mg/m2, cytosine arabinoside < 100 mg/m2/day, asparaginase (non-pegylated)

The following drugs must be stopped >2 weeks prior to CTL019 infusion:

salvage chemotherapy (e.g. clofarabine, cytosine arabinoside > 100 mg/m2,
anthracyclines, cyclophosphamide), excluding the required lymphodepleting
chemotherapy drugs Pegylated-asparaginase must be stopped > 4 weeks prior to
CTL019 infusion

5. CNS disease prophylaxis:

CNS prophylaxis treatment must be stopped > 1 week prior to CTL019 infusion (e.g.
intrathecal methotrexate)

- Anti T-cell therapy: Administration of any T cell or toxic agent is strongly
discouraged since residual lytic levels may destroy the infused CTL019 cell or prevent
their in vivo expansion.

Other protocol-defined inclusion/exclusion may apply.