Phase IIa Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCRz and 4-Signaling Domains in Patients With Chemotherapy Relapsed or Refractory CD19+ Lymphomas

Inclusion Criteria

- Male or female subjects with CD19+ B cell lymphomas with no available curative
treatment options (such as autologous or allogeneic SCT) who have a limited prognosis
(several months to <2 year survival) with currently available therapies will be
enrolled. The study will enroll 51 evaluable subjects as follows:

- CD19+ Lymphoma

Cohort A Subjects:

a. Follicular lymphoma, previously identified as CD19+ i. At least 2 prior chemotherapy or
immunochemotherapy regimens (not including single agent monoclonal antibody therapy) ii.
Patients who progress within 2 years after second or higher line of therapy will be
eligible. For instance, patients who have progression of lymphoma < 2 years after second or
greater line therapy, but who have responded to their most recent treatment (3rd line or
higher) will be eligible. Patients may have progression, stable disease or responding
disease at the time of enrollment.

iii. Patients with a history of large cell transformation are eligible. b. Mantle cell
lymphoma, previously identified as CD19+ i. Beyond 1st CR with relapsed disease,
progressive disease during first line rituximab-chemotherapy combination, or persistent
disease after first line rituximab-chemotherapy combination and not eligible or appropriate
for conventional allogeneic or autologous SCT.

ii. Relapsed after prior autologous SCT. c. Diffuse large B cell lymphoma, previously
identified as CD19+ i. Residual disease after primary therapy and not eligible for
autologous SCT ii. Relapsed or persistent disease after prior autologous SCT iii. Beyond
1st CR with relapsed or persistent disease and not eligible or appropriate for conventional
allogeneic or autologous SCT iv. Patients with an antecedent history of follicular lymphoma
or CLL/SLL are eligible.

Cohort B Subjects:

a. Diffuse large B cell lymphoma, previously identified as CD19+ CD19 i. Residual disease
after primary therapy and not eligible for autologous SCT ii. Relapsed or persistent
disease after prior autologous SCT iii. Beyond 1st CR with relapsed or persistent disease
and not eligible or appropriate for conventional allogeneic or autologous SCT iv. Patients
with an antecedent history of follicular lymphoma or CLL/SLL are eligible.

v. Patients with T cell/histiocyte-rich disease as confirmed by surgical pathology report

Cohort C Subjects:

a. Diffuse large B cell lymphoma, previously identified as CD19+ i. Residual disease after
primary therapy and not eligible for autologous SCT ii. Relapsed or persistent disease
after prior autologous SCT iii. Beyond 1st CR with relapsed or persistent disease and not
eligible or appropriate for conventional allogeneic or autologous SCT iv. Patients with an
antecedent history of follicular lymphoma or CLL/SLL are eligible.

- Age ≥18 years

- Creatinine < 1.6 mg/dL

- ALT/AST < 3x upper limit of normal

- Bilirubin <2.0 mg/dL, unless subject has Gilbert's Syndrome (<3.0 mg/dL)

- Any relapse after prior autologous SCT will make patient eligible regardless of other
prior therapy.

- Patients with relapsed disease after prior allogeneic SCT (myeloablative or
non-myeloablative) will be eligible if they meet all other inclusion criteria and:

1. Have no active GVHD and require no immunosuppression

2. Are more than 6 months from transplant

- Measurable or assessable disease according to the "Revised Response Criteria for
Malignant Lymphoma" (Cheson et al., J. Clin. Onc., 1999)108. Patients in complete
remission with no evidence of disease are not eligible.

- Performance status (ECOG) 0 or 1.

- Left Ventricle Ejection Fraction (LVEF) > 40% confirmed by ECHO/MUGA

- Written informed consent is given. Successful T cell test expansion (first 10
subjects).

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
pregnancy test at enrollment. A urine pregnancy test will be 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. For additional details regarding use of steroids

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

- Class III/IV cardiovascular disability according to the New York Heart Association
Classification (see Appendix 1).

- HIV infection.

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

- Patients in complete remission with no assessable disease.

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