Allo CART-19 Protocol

The investigators propose an open label, single center, pilot study to evaluate the safety
and tolerability, and persistence of donor lymphocytes engineered to express a chimeric
antigen receptor targeting CD19 which is linked to the CD3:4-1BB signaling chains in
patients with CD19+ acute lymphoblastic leukemia (ALL). Upon enrollment, donors will undergo
leukapheresis and patients will undergo an optional bone marrow/lymph node biopsy
approximately four weeks prior to dosing. Between dosing and treatment, patients may undergo
an additional chemotherapy treatment depending upon their disease. At dosing, patients will
receive redirected donor lymphocytes targeted against CD19 (allo-CART-19 cells). The cell
dose will be given as a split infusion over three days to enhance the ability to manage any
infusion related toxicity. Patients will be monitored weekly for four weeks. At the end of
four weeks, patients will undergo a second leukapheresis and second optional bone
marrow/lymph node biopsy. At this point the patient will also undergo restaging. Observation
and monitoring of patients will continue on a monthly basis until week 24 post dosing.
Annual follow-up for lentiviral vector safety will be carried out for 15 years in accordance
with FDA guidelines for retroviral vectors. Ten subjects will be targeted for this study,
with an expected rate of drop out of 30% due to disease progression between enrollment and
week four post dosing.

Inclusion Criteria:

- CD19+ ALL relapsed after allogeneic SCT.

- No active GVHD and off immunosuppression for greater than or equal to 4 weeks.

- Age greater than or equal to 18 years.

- Creatinine less than or equal to2.5 mg/dl.

- ALT/AST less than or equal to3x normal

- Bilirubin less than or equal to2.0 mg/dl

- Donor is available and is able to undergo apheresis. A separate donor consent process
and form is described below.

- Voluntary informed consent is given.

Exclusion Criteria:

- Pregnant or lactating women. The safety of this therapy on unborn children is not
known. Female study participants of reproductive potential must have a negative serum
or urine pregnancy test performed within 48 hours before infusion.

- Uncontrolled active infection.

- Active hepatitis B or hepatitis C infection.

- Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not
exclusionary.

- Previously treatment with any gene therapy products.

- Feasibility assessment during screening demonstrates less than 30% transduction of
target lymphocytes, or insufficient expansion ( less than 5-fold) in response to
CD3/CD28 costimulation..

- Any uncontrolled active medical disorder that would preclude participation as
outlined.

- HIV infection.

- Patients with active CNS involvement with leukemia. Patients with prior CNS disease
that has been effectively treated will be eligible providing treatment was greater
than or equal to 4 weeks before enrollment

- Patients with active GVHD or requiring immune suppression.