A Feasibility and Safety Study of Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy for CD19+CD22+ Leukemia

Inclusion Criteria:

- First 2 subjects: male and female subjects age ≥18 and < 27 years (as of 2/16/18 the
first 2 subjects were enrolled and treated); subsequent subjects: male and female
subjects age ≥12 months of age and <27 years.

- Diagnosis of CD19+22+ leukemia

- Disease status:

- If post allogeneic HCT: Confirmed CD19+CD22+ leukemia recurrence defined as at
least 0.01% disease following allogeneic HCT

- If relapse/refractory status with no prior history of allogeneic HCT, one of the
following:

- Second or greater marrow relapse, with or without extramedullary disease

- First marrow relapse at end of first month or re-induction with marrow having at
least 0.01 % blasts by morphology and/or MPF

- Primary refractory as defined as greater than 5% blasts by multi-parameter flow
after at least 2 separate induction regimens.

- Subject has indication for HCT but has been deemed ineligible, inclusive of
persistent MRD prior to HCT

- Asymptomatic from CNS involvement, if present, and in the opinion of the Principal
Investigator with a reasonable expectation that disease burden can be controlled in
the interval between enrollment and T-cell infusion. Subjects with significant
neurologic deterioration will not be eligible for T-cell infusion until stabilized.

- Free from active GVHD and off immunosuppressive GVHD therapy for 4 weeks prior to
enrollment

- Lansky or Karnofsky performance score of at least 50

- Life expectancy of at least 8 weeks

- Recovered from acute toxic effects of all prior chemotherapy, immunotherapy, and
radiotherapy

- At least 7 days post last chemotherapy administration (excluding intrathecal
maintenance chemotherapy)

- At least 7 das post last systemic corticosteroids administration (unless physiologic
replacement dosing)

- No prior genetically modified cell therapy that is still detectable or virotherapy

- Adequate organ function

- Adequate laboratory values

- Willing to participate in long-term follow-up for up to 15 years, if enrolled in the
study and receive T cell infusion

- Patients of childbearing/fathering potential must agree to use highly effective
contraception from the time of initial T cell infusion through 12 months following the
last T cell infusion

Exclusion Criteria:

- Presence of active clinically significant CNS dysfunction

- Pregnant or breast-feeding

- Unable to tolerate apheresis procedure

- Presence of active malignancy other than CD19+CD22+ leukemia

- Presence of active severe infection

- Presence of any concurrent medical condition that, in the opinion of the Principal
Investigator, would prevent the patient from undergoing protocol-specified therapy