Precursor B Cell Acute Lymphoblastic Leukemia (B-ALL) Treated With Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19

• To assess the anti-leukemic effect of adoptively transferred anti-CD19 T cells. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• To assess the in vivo survival of gene-modified anti-CD19 T cells. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

This study is an investigational approach that uses immune cells, called "T cells", to kill leukemia. These T cells are removed from blood, modified in a laboratory, and then put back in the body. T cells fight infections and can also kill cancer cells in some cases. However, right now T cells are unable to kill the cancer cells. For this reason we will put one gene into the T cells that allows them to recognize and kill the leukemia cells. This gene will be put in the T cells by a weakened virus. The gene will produce proteins in the T cells that help the T cells recognize the leukemia cells and possibly kill them. The doctors have found that T cells modified in this way can cure an ALL-like cancer in mice.

The main goals of this study is to determine the safety of these modified T cells in patients with ALL. This will be done in a "clinical trial." If too many serious side effects are seen with the initial dose, and some additional patients may be treated with a lower dose to make sure that this dose is safe. The patient will also receive chemotherapy before the T cells. We will use normally chemotherapy that is used in patients with leukemia. The chemotherapy is given to reduce leukemia and to allow the T cells to live longer.

• Leukemia
• Acute Lymphoblastic Leukemia

Inclusion Criteria:

• Adult patients are eligible (> or = to 18 year old).
• Patients must have ALL refractory, relapsed, MRD, or in first CR as described below.
• Complete remission is defined as restoration of normal hematopoiesis with a neutrophil count > 1,000 x 106/L, a platelet count > 100,000 x 106/L, and hemoglobin > 10 g/dL. Blasts should be < 5% in a post-treatment bone marrow differential. Furthermore, there should be no clinical evidence of leukemia for a minimum of four weeks.
• MRD is defined as patients meeting the criteria for CR above, but with residual disease measured by a quantitative PCR, done by the Molecular Pathology Facility at MSKCC. or by flow cytometry performed by the Cell Marker Laboratory at MSKCC, or by deep-sequencing of the IgH rearrangements done by an accredited outside facility. The assay from blood and/or bone marrow defines MRD by qPCR as a cycle threshold (CT) that is at least 1 CT value < than the lowest CT value from the background. Outside laboratory tests may suffice for this assessment at the discretion of the Principal Investigator.

Relapsed B-ALL will be defined as patients that meet the above criteria for a CR before developing recurrent disease (increased bone marrow blasts). Refractory patients will be defined as patients that have not achieved a CR after 2 cycles of induction chemotherapy

• Patients must have a diagnosis of B-ALL by flow cytometry, or bone marrow histology, and/or cytogenetics. These studies are to be performed at Memorial Hospital.
• Patients must have CD19+ ALL as confirmed by flow cytometry.
• Creatinine < 2.0 mg/100 ml, bilirubin < 2.0 mg/100 ml, AST and ALT < 3x normal, PT and PTT < 2x normal outside the setting of stable chronic anticoagulation therapy.
• Adequate cardiac function (LVEF > 40%) as assessed by ECHO or MUGA performed within 1 month of enrollment.
• Adequate pulmonary function as assessed by > 92% oxygen saturation on room air by pulse oximetry.
• Patients must have adequate access for leukapheresis procedure as assessed by staff from the MSKCC Donor Room.
• Life expectancy > 3 months

Exclusion Criteria:

• Karnofsky performance status < 70.
• Patients previously treated with an allogeneic SCT that is currently complicated by active GVHD requiring T cell suppressive therapy.
• Patients with HIV, hepatitis B or hepatitis C infection.
• Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation.