At entry subjects will be staged and the suitability of their T cells for CART-19
manufacturing will be determined. Subjects who have adequate T cells will be leukapheresed
to obtain large numbers of peripheral blood mononuclear cells (PBMC) for CART-19
manufacturing. The T cells will be purified from the PBMC, transduced with CART-19
lentiviral vector, expanded in vitro and then frozen for future administration. Chemotherapy
will then be given. Following tumor burden reassessment, CART-19 cells will be thawed and
Subjects will have blood tests to assess safety, and engraftment and persistence of the
CART-19 cells at regular intervals through four weeks after their last infusion of the
study. Following the 6 months of intensive follow-up, subjects will be evaluated quarterly
for two years with a medical history, a physical examination, and blood tests. Following
this evaluation, subjects will enter a roll-over study for annual follow-up by phone and
questionnaire for an additional thirteen years to assess for the diagnosis of long-term
health problems, such as development of new malignancy.
1. Determine the safety and feasibility of administration of chimeric antigen receptor T
cells transduced with the anti-CD 19 lentiviral vector (referred to as "CART-19"
2. Determine duration of in vivio survival of CART-19 cells. Real Time polymerase chain
receptor (RT-PCR) analysis of whole blood will be used to detect and quantify survival
of CART-19 TCR:4-1BB and TCR cells over time.
1. For patients with detectable disease, measure anti-tumor response due to CART-19 cell
2. To determine if the 4-1BB transgene is superior to the TCR only transgene as measured
by the relative engraftment levels of CART-19 TCR:4-1BB and TCR cells over time.
3. For patients with stored or accessible tumor cells (such as patients with active
chronic lymphocytic leukemia (CLL), acute lymphoblastic leukema (ALL), etc) determine
tumor cell killing by CART-19 cells in vitro.
4. Determine if cellular or humoral host immunity develops against the murine anti-CD19,
and assess correlation with loss of detectable CART-19 (loss of engraftment).
5. Determine the relative subsets of CART-19 T cells (Tcm, Tem, and Treg)
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
1. Eligible diseases: CD19+ leukemia or lymphoma
a. ALL without curative options for therapy, including those not eligible for
allogeneic SCT because of: i. age ii. comorbid disease iii. other contraindications
to TBI-based conditioning (required for ALL SCT) iv. lack of suitable donor v. prior
SCT vi. 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
. 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.
b. Diffuse large cell lymphoma or other high-grade NHL, previously identified as
CD19+ i. Residual disease after primary therapy and not eligible for autologous SCT.
ii. Relapsed after prior autologous SCT. iii. Beyond 1st CR with relapsed or
persistent disease and not eligible or appropriate for conventional allogeneic or
2. 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.
3. Expected survival > 12 weeks
4. Creatinine < 2.5 mg/dl and less than 2.5x normal for age
5. ALT <= 5x normal
6. Bilirubin <2.0 mg/dl
7. Any relapse after prior SCT will make patient eligible regardless of other prior
8. Patients with relapsed disease after prior allogeneic SCT (myeloablative or
non-myeloablative) will be eligible if they meet all other inclusion criteria and
1. Have no active GVHD and require no immunosuppression
2. Are more than 4 months from transplant (6 months at infusion)
9. 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
10. Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy.
10. Voluntary informed consent is given.
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, or hydrocortisone for physiological replacement in patients with
adrenal insufficiency are permitted as well.
5. Presence of grade 2-4 acute or extensive chronic GVHD.
6. Under treatment for GVHD.
7. Previous treatment with any gene therapy products.
8. Feasibility assessment during screening shows insufficient expansion in response to
9. Any uncontrolled active medical disorder that would preclude participation as
10. HIV infection.
11. Patients with active CNS involvement with malignancy (i.e. CNS3 for ALL). Patients
with prior CNS disease that has been effectively treated will be eligible. Routine
CNS prophylaxis for ALL is permitted.
Minimum Eligible Age: 1 Year
Maximum Eligible Age: 24 Years
Eligible Gender: Both