Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCR and 4-1BB Signaling Domains in Patients With Chemotherapy Resistant or Refractory Acute Lymphoblastic Leukemia

Inclusion Criteria

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

- Relapsed or refractory B-cell ALL

1. 1st or greater BM relapse OR

2. Any marrow relapse after allogeneic HSCT and > 100 days from transplant OR

3. For patients with refractory disease:

i. < 60 years old that have not achieved a CR after > 2 or more chemotherapy regimens
ii. >60 years old that have not achieved a CR after 1 prior chemotherapy regimen d.
Patients with Ph+ ALL are eligible if they have failed tyrosine kinase inhibitor
therapy

- Documentation of CD19 tumor expression in bone marrow or peripheral blood by flow
cytometry within 3 months of screening.

- Adequate organ function defined as:

1. Creatinine < 1.6 mg/dl

2. ALT/AST < 3x upper limit of normal range

3. Direct bilirubin <2.0 mg/dl

4. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea,
pulse oxygen > 92% on room air, and DLCO > 40% (corrected for anemia if
clinically appropriate)

5. Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA

- Bone marrow with ≥ 5% lymphoblasts

- Male or female age ≥ 18 years

- A ECOG Performance Status that is either 0 or 1

- No contraindications for leukapheresis.

Retreatment Inclusion Criteria

- Performance Status 0-1

- Adequate organ system function including:

- Creatinine < 1.6 mg/dl

- ALT/AST < 3x upper limit of normal

- Total Bilirubin < 2.0 mg/dl

- Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea,
pulse oxygen > 92% on room air, and DLCO > 40% (corrected for anemia if
clinically appropriate)

- Left Ventricular Ejection Fraction ≥ 40%

- No contraindications for leukapheresis (if required for retreatment)

- Gives voluntary informed consent for retreatment

Exclusion Criteria

- Isolated extramedullary disease relapse

- Active hepatitis B or active hepatitis C

- Class III/IV cardiovascular disability according to the New York Heart Association
Classification

- HIV infection

- Active acute or chronic graft-versus-host disease (GVHD) or requirement of
immunosuppressant medications for GVHD within 4 weeks of enrollment.

- Concurrent use of systemic steroids or chronic use of immunosuppressant medications.
Recent or current use of inhaled steroids is not exclusionary. For additional details
regarding use of steroid and immunosuppressant medications.

- Active CNS involvement by malignancy. Note: Patients with history of CNS disease that
has been effectively treated will be eligible provided that treatment was >4 weeks
before enrollment

- Pregnant or nursing (lactating) women, female study participants of reproductive
potential must have a negative serum or urine pregnancy test within 48 hours before
infusion

- Participation in a prior investigational study within 4 weeks prior to enrollment or
longer if required by local regulation. Participation in non-therapeutic research
studies is allowed.

- Patients with a known history or prior diagnosis of optic neuritis or other
immunologic or inflammatory disease affecting the central nervous system.

Retreatment Exclusion Criteria

- Pregnant or lactating women.

- Active hepatitis B or hepatitis C

- Concurrent use of systemic steroids or chronic use of immunosuppressant medications.
Recent or current use of inhaled steroids is not exclusionary. For additional details
regarding use of steroid or immunosuppressant medications.

- HIV infection

- Patients with active CNS involvement with malignancy. Patients with prior CNS disease
that has been effectively treated will be eligible providing treatment was >4 weeks
before enrollment on the retreatment cohort.

- Class III/IV cardiovascular disability according to the New York Heart Association
Classification

- Patients with a known history or prior diagnosis of optic neuritis or other
immunologic or inflammatory disease affecting the central nervous system.