Study of Efficacy and Safety of Tisagenlecleucel in HR B-ALL EOC MRD Positive Patients

Inclusion Criteria:

1. CD19 expressing B-cell Acute Lymphoblastic Leukemia

2. De novo NCI HR B-ALL who received first-line treatment and are MRD ≥ 0.01% at EOC.EOC bone marrow MRD will be collected prior to screening and will be assessed bymulti-parameter flow cytometry using central laboratory analysis.

3. Age 1 to 25 years at the time of screening

4. Lansky (age < 16 years) or Karnofsky (age ≥ 16 years) performance status ≥ 60%

5. Adequate organ function during the screening period: A. Renal function based on age/gender B. ALT ≤ 5 times ULN for age C. AST ≤ 5 timesULN for age D. Total bilirubin < 2 mg/dL (for Gilbert's Syndrome subjects totalbilirubin < 4 mg/dL) E. Adequate pulmonary function defined as:

• no or mild dyspnea (≤ Grade 1)

• oxygen saturation of > 90% on room air F. Adequate cardiac function defined asLVSF ≥ 28% confirmed by echocardiogram or LVEF ≥ 45% confirmed byechocardiogram or MUGA within 6 weeks of screening

6. Prior induction and consolidation chemotherapy allowed: 1st line subjects: ≤ 3blocks of standard chemotherapy for first-line B-ALL, defined as 4-drug induction,Berlin-Frankfurt-Münster (BFM) consolidation or Phase 1b, and interim maintenancewith high-dose methotrexate.

Exclusion Criteria:

1. M3 marrow at the completion of 1st line induction therapy

2. M2 or M3 marrow or persistent extramedullary disease at the completion of first-lineconsolidation therapy or evidence of disease progression in the peripheral blood ornew extramedullary disease prior to enrollment. Patients with previous CNS diseaseare eligible if there is no active CNS involvement of leukemia at the time ofscreening.

3. Philadelphia chromosome positive ALL

4. Hypodiploid: less than 44 chromosomes and/or DNA index < 0.81, or other clearevidence of a hypodiploid clone

5. Prior tyrosine kinase inhibitor therapy

6. Subjects with concomitant genetic syndromes associated with bone marrow failurestates: such as subjects with Fanconi anemia, Kostmann syndrome, Shwachman syndromeor any other known bone marrow failure syndrome. Subjects with Down syndrome willnot be excluded.

7. Subjects with Burkitt's lymphoma/leukemia (i.e. subjects with mature B-ALL, leukemiawith B-cell [sIg positive and kappa or lambda restricted positivity] ALL, with FABL3 morphology and /or a MYC translocation)

8. Has had treatment with any prior anti-CD19 therapy 9. Treatment with any prior geneor engineered T cell therapy

Other protocol-defined inclusion/exclusion may apply.