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