Allogeneic Second-generation CD19-CAR T Cells for Pediatric Relapsed/Refractory B-ALL

Patient Inclusion Criteria:

1. Patients with a diagnosis of CD19 expressing B ALL relapse, and one of thefollowing:

2. Relapse after alloHSCT OR

3. Relapsed/refractory disease, with failure of frontline therapy and at least 2rescue strategies, including CD19/CD22-directed monoclonal antibody andavailability of a fully matched related donor.

4. CD19+ count ≥ 50 cells/mcl and/or Minimal Residual Disease (MRD) ≥ 10^-4.

5. Voluntary informed consent. For subjects < 18-years old their legal guardian mustgive informed consent. Pediatric subjects will be included in age-appropriatediscussion and verbal assent will be obtained for those greater than or equal to 12years of age, when appropriate.

6. Clinical performance status: patients > 16 years of age: Karnofsky greater than orequal to 60%; patients ≤ 16 years of age: Lansky score than or equal to 60%.

7. Patients of child-bearing or child-fathering potential must be willing to practicebirth control from the time of enrollment on this study and for 4 months afterreceiving the lymphodepletion regimen.

8. Females of child-bearing potential must have a negative pregnancy test because ofthe potentially dangerous effects on the fetus.

Patients Exclusion Criteria:

1. Pregnant or lactating women.

2. Severe, uncontrolled active intercurrent infections.

3. HIV, or active HCV and/or HBV infection.

4. Life-expectancy < 6 weeks or rapidly progressive disease that in the evaluation ofthe investigator would compromise ability to complete study therapy.

5. Hepatic function: inadequate liver function defined as total bilirubin > 4x upperlimit of normal (ULN) or transaminase (ALT and AST) > 6x ULN.

6. Renal function: serum creatinine >3x ULN for age.

7. Blood oxygen saturation < 90%.

8. Cardiac function: left ventricular ejection fraction lower than 45% by ECHO.

9. Congestive heart failure, cardiac arrhythmia, psychiatric illness, or socialsituations that would limit compliance with study requirements or in the opinion ofthe PI would pose an unacceptable risk to the subject.

10. Presence of active, grade 2-4 acute or chronic Graf versus Host Disease (GvHD)requiring steroid therapy or other immune-suppressive treatment.

11. Relapse occurring before 60 days after alloHSCT.

12. Concurrent or recent prior therapies, before infusion: i. systemic steroids (at a dose of ≥ 2 mg/kg prednisone) in the 2 weeks beforeinfusion of CD19-CAR_Lenti_ALLO cells . Recent or recurrent use ofinhaled/topical/non-absorbable steroids is not exclusionary.

ii. systemic chemotherapy in the 2 weeks preceding infusion of CD19-CAR_Lenti_ALLO cells .

iii. anti-thymocyte globulin (ATG) or Alemtuzumab (Campath®)in the 8 weeks preceding infusion of CD19-CAR_Lenti_ALLO cells .

iv. immuno-suppressive agentis in the 2 weeks preceding infusion of CD19-CAR_Lenti_ALLO cells

v. radiation therapy must have been completed at least 2 weeks before infusion of CD19-CAR_Lenti_ALLO cells .

vi. other anti-neoplastic investigational agents currently administered or within 30 days prior to infusion of CD19-CAR_Lenti_ALLO cells (i.e, start of protocol therapy).

vii. Exceptions:

1. there is no time restrictions in regards to intrathecal chemotherapy, but there mustbe a complete recovery from any acute toxic effects from such treatment.

2. subjects receiving steroid therapy at physiologic replacement doses only are allowedprovided that there has been no increase for at least 2 weeks to starting apheresis.

Donor Eligibility Criteria

Conventional criteria for the eligibility of allogeneic donors will be adopted for the evaluation of cell donors, before apheresis, as required by law.