Phase I/IIA Study of CART19 Cells for Patients With Chemotherapy Resistant or Refractory CD19+ Leukemia and Lymphoma

Inclusion Criteria:

Male and female subjects with CD 19+ 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:

Eligible diseases: CD 19+ leukemia or lymphoma

ALL without curative options for therapy, including those not eligible for allogeneic

SCT because of:

age
co-morbid disease
other contraindications to TBI-based conditioning (required for ALL SCT)
lack of suitable donor
prior SCT
Declines allo SCT (in CR3) as a therapeutic option after documented discussion about the role of SCT with a BMT physician not part of the study team. Note: Patient may be in any complete response, or patient may have active disease but responding or stable after most recent therapy. The intent is not to enroll patients with no degree of disease control, or rapidly increasing disease burden between enrollment and cell infusion.

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 24 years. Patients ages 22-24 will only be enrolled if they are currently being treated at CHOP or another pediatric facility/oncologist
Expected survival > 12 weeks
Creatinine < 2.5 mg/dl and less than 2.5x normal for age
ALT ≤ 5x normal
Bilirubin <2.0 mg/dl
Any relapse after prior 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 no active GVHD and require no immunosuppression
Are more than 4 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
Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy (at infusion)

Exclusion Criteria:

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 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, or hydrocortisone for physiological replacement in patients with adrenal insufficiency are permitted as well
Presence of grade 2-4 acute or extensive chronic GVHD
Under treatment for GVHD
Previous treatment with any gene therapy products
Any uncontrolled active medical disorder that would preclude participation as outlined.
HIV infection.
CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity