Pilot Study of Redirected Autologous T-cells Engineered to Contain Anti-CD19 Attached to TCR and 4-1BB Signaling Domains in Patient With Chemotherapy Resistant or Refractory CD19+ Leukemia and Lymphoma

Inclusion Criteria

Inclusion

- Male and female subjects with CD19+ B cell malignancies in patients with no available
curative treatment options (such as autologous or allogeneic SCT) who have limited
prognosis (several months to < 2 year survival) with currently available therapies
will be enrolled

- CD19+ leukemia or lymphoma

- ALL in CR2 or CR3 and not eligible for allogeneic SCT because of age, comorbid
disease, or lack of available family member or unrelated donor

- Follicular lymphoma, previously identified as CD19+:

- At least 2 prior combination chemotherapy regimens (not including single agent
monoclonal antibody (Rituxan) therapy

- Stage III-IV disease

- Less than 1 year between last chemotherapy and progression (i.e. most recent
progression free interval < 1 year)

- Disease responding or stable after most recent therapy (chemotherapy, MoAb, etc)

- CLL:

- At least 2 prior chemotherapy regimens (not including single agent monoclonal
antibody (Rituxan) therapy. Patients with high risk disease manifested by deletion
chromosome 17p will be eligible if they fail to achieve a CR to initial therapy or
progress within 2 years of 1 prior

- Less than 2 years between last chemotherapy and progression (i.e. most recent
progression free interval < 2 years)

- Not eligible or appropriate for conventional allogeneic SCT

- Patients who achieve only a partial response to FCR as initial therapy will be
eligible.

- Mantle cell lymphoma:

- Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for
conventional allogeneic or autologous SCT

- Disease responding or stable after most recent therapy (chemotherapy, MoAb, etc...)

- Relapsed after prior autologous SCT

- B-cell prolymphocytic leukemia (PLL) with relapsed or residual disease after at least
1 prior therapy and not eligible for allogeneic SCT

- Diffuse large cell lymphoma, previously identified as CD19+:

- Residual disease after primary therapy and not eligible for autologous SCT

- Relapsed after prior autologous SCT

- Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate of
conventional allogeneic or autologous SCT

- Expected survival > 12 weeks

- Creatinine < 2.5 mg/dl

- ALT/AST < 3x normal

- Bilirubin < 2.0 mg/dl

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

- Adequate venous access for apheresis, and no other contraindications for
leukapheresis

- Voluntary informed consent is given

Exclusion

- 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 < 30% transduction of target
lymphocytes, or insufficient expansion (< 5-fold) in response to CD3/CD28
costimulation

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

- HIV infection