CD22 Redirected Autologous T Cells for ALL

1. Signed informed consent form must be obtained prior to any study procedure.

2. Relapsed or refractory B-cell ALL:

3. 2nd or greater relapse OR

4. Any marrow or extramedullary relapse after allogeneic HSCT and ≥ 6 months fromSCT at infusion OR

5. Any marrow relapse after CAR-modified T cell therapy OR

6. Refractory disease defined as having not achieved a CR after > 2 chemotherapyregimens OR

7. Patients with Ph+ ALL are eligible if they are intolerant to or have failedtyrosine kinase inhibitor therapy OR

8. Ineligible for allogeneic SCT because of: i. Comorbid disease ii. Other contraindications to allogeneic SCT conditioningregimen iii. Lack of suitable donor iv. Prior SCT v. Declines allogeneic SCT as atherapeutic option after documented discussion, with expected outcomes, about therole of SCT with a BMT physician not part of the study team g. Patients with CNS3disease will be eligible if CNS disease is responsive to therapy (at infusion, mustmeet criteria in Section 5.2)

9. Documentation of CD22 tumor expression in bone marrow, other tumor biopsy, CSF orperipheral blood by flow cytometry (or a recent marrow in the case of refractorydisease). If the patient has received CD22-directed therapy (i.e., inotuzumab), thenthe marrow or other sample should be obtained after this therapy to show CD22expression.

10. Adequate organ function defined as: a. A serum creatinine based on age/gender as follows:

11. A serum creatinine based on age/gender as follows:Maximum Serum Creatinine (mg/dL) Age 1 to < 2 years Male 0.6 Female 0.6 Age 2to < 6 years Male 0.8 Female 0.8 Age 6 to < 10 years Male 1.0 Female 1.0 Age 10to < 13 years Male 1.2 Female 1.2 Age 13 to < 16 years Male 1.5 Female 1.4 Age ≥ 16 years Male 1.7 Female 1.4

12. Adequate liver function i. ALT < 500 U/L ii. Bilirubin <3x upper limit of normal iii. ALT and/or bilirubin that exceed these ranges is acceptable if, in the opinionof the investigator (or by liver biopsy), the abnormalities are directly related toALL infiltration of the liver c. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea,pulse oxygen > 92% on room air; DLCO > 40% (corrected for anemia) if PFTs areclinically appropriate as determined by the treating investigator d. Left Ventricle Shortening Fraction (LVSF) ≥ 28% or Ejection Fraction (LVEF) ≥ 40%confirmed by ECHO/MUGA; in cases where quantitative assessment of LVEF is notpossible, a statement by the cardiologist that the ECHO shows qualitatively normalventricular function will suffice.

13. Evidence of disease by standard morphologic or by MRD criteria. If the results of ahistorical biopsy (obtained at the time of the patient's most recent relapse) areavailable, this does not need to be repeated at screening.

14. Age 1-29 years.

15. Adequate performance status (Lansky or Karnofsky score ≥50).

16. Subjects of reproductive potential must agree to use acceptable birth controlmethods.

Exclusion Criteria:

1. Active hepatitis B or active hepatitis C.

2. HIV Infection.

3. Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy.

4. Concurrent use of systemic steroids or immunosuppressant medications. Recent orcurrent use of inhaled steroids or physiologic replacement with hydrocortisone isnot exclusionary.

5. CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions thatmight increase the risk of CNS toxicity.

6. Pregnant or nursing (lactating) women.

7. Receipt of a prior investigational study agent within 4 weeks prior to screeningvisit. *Note - patients who have received anti-CD19 CART cells (e.g., CART19/CTL019)on an investigational study where cell infusion occurred greater than 4 weeks beforethe screening visit are NOT excluded.