Pilot Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCRζ and 4-1BB Signaling Domains in Patients With Chemotherapy Resistant or Refractory CD19+ Leukemia and Lymphoma (Pedi CART-19)

Inclusion Criteria:

• CD19+ leukemia or lymphoma
• ALL without curative options for therapy, including those not eligible for allogeneic SCT because of age, comorbid disease, lack of suitable donor or prior SCT.
• Patient may be in any complete response, or
• Patient may have active disease but responding or stable after most recent therapy
• 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).
• CLL
• At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy.
• Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval <1 year).
• Not eligible or appropriate for conventional allogeneic SCT.
• Disease responding or stable after most recent therapy (chemotherapy, MoAb)
• 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).
• 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 or other high-grade NHL, 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 for conventional allogeneic or autologous SCT.
• Age 1 to 21 years.
• Expected survival > 12 weeks
• Creatinine < 2.5 mg/dl and less than 2.5x normal for age
• ALT/AST < 3x normal
• Bilirubin <2.0 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
• Have reverted to recipient hematopoiesis (no evidence of donor cells by STR analysis on 2 occasions separated by at least 1 month).
• Have no active GVHD and require no immunosuppression
• Are more than 6 months from transplant
• For those patients who require leukapheresis for T cell collection (i.e. no previously collected product exists), adequate venous access for apheresis or eligible for appropriate catheter placement, and no other contraindications for leukapheresis.
• Voluntary informed consent is given.

Exclusion Criteria:

1. 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.
2. Uncontrolled active infection.
3. Active hepatitis B or hepatitis C infection.
4. Concurrent use of systemic steroids at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of inhaled steroids is permitted as well.
5. Previously treatment with any gene therapy products.
6. Feasibility assessment during screening demonstrates<30% transduction of target lymphocytes, or insufficient expansion (<5-fold) in response to CD3/CD28 costimulation.
7. Any uncontrolled active medical disorder that would preclude participation as outlined.
8. HIV infection.
9. Patients with active CNS involvement with malignancy. Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was >4 weeks before enrollment