Genetically Engineered Lymphocyte Therapy in Treating Patients With B-Cell Leukemia or Lymphoma That is 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