CART19 to Treat B-Cell Leukemia or Lymphoma That Are Resistant or Refractory to Chemotherapy

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