Study of huCART19 for Very High-Risk (VHR) Subsets of Pediatric B-ALL

Inclusion Criteria:

Relapsed or refractory B-cell ALL:

- Cohort A: Patients with newly diagnosed VHR B-ALL or high-risk relapse of B-ALL who
meet one of the following criteria:

- Newly diagnosed NCI HR B-ALL with induction failure: M3 marrow (>25% blasts) at
end of induction OR

- First marrow relapse of B-ALL at < 36 months from diagnosis OR

- 2nd or greater relapse OR

- Any relapse after allogeneic hematopoietic stem cell transplantation (HSCT) and ≥
4 months from stem cell transplant (SCT) at enrollment OR

- Refractory disease defined as having not achieved a minimal residual disease
(MRD)_-negative and/or cerebral spinal fluid (CSF)-negative complete response
(CR) after ≥ 2 chemotherapy regimens/cycles of frontline therapy or 1 cycle of
reinduction therapy for patients in first relapse OR

- Ineligible for allogeneic stem cell transplant

- Cohort B: Patients previously treated with B cell directed engineered cell therapy who
meet one of the following criteria:

- partial response or no response to prior cell therapy

- CD19+ relapse after prior cell therapy

- demonstrated early (≤6 months from infusion) B cell recovery suggesting loss of
engineered cells

- Patients with prior or current history of CNS3 disease will be eligible if central
nervous system (CNS) disease is responsive to therapy

- Documentation of CD19 tumor expression in bone marrow, peripheral blood, CSF, or tumor
tissue by flow cytometry at relapse

- Adequate organ function

- Age 1-29 years

- Adequate performance status

Exclusion Criteria:

- Active hepatitis B or active hepatitis C.

- HIV Infection.

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

- Concurrent use of systemic steroids at the time of cell infusion or cell collection,
or a condition, in the treating physician's opinion, that is likely to require steroid
therapy during collection or after infusion. Steroids for disease treatment at times
other than cell collection or at the time of infusion are permitted. Use of
physiologic replacement hydrocortisone or inhaled steroids is permitted as well.

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

- Pregnant or nursing (lactating) women.

- Uncontrolled active infection.