Activated T Lymphocytes Expressing CARs, Relapsed CD19+ Malignancies Post-Allo HSCT(CARPASCIO)

The subject or his/her donor will give blood to make CD19/CD28 chimeric receptor-T cells in
the laboratory. These cells will be grown and frozen. To make the T cells, the
donor/subject's blood will be stimulated with growth factors to make the T cells grow. To get
the CD19 antibody with CD28 to attach to the surface of the T cell, an antibody gene will be
inserted into the T cell. This is done with a virus called a retrovirus that has been made
for this study and will carry the antibody gene into the T cell. This virus also helps
investigators find the T cells in the blood using a special laboratory test. Subjects will be
followed for a total of 15 years to see if there are any long term side effects of gene
transfer.

When a subject enrolls on this study, s/he will be assigned a dose of CD19/CD28 chimeric
receptor-T cells and should not receive other cancer treatment until 6 weeks after cell
infusion.

Several studies suggest that the infused T cells need room to be able to proliferate and
accomplish their functions and that this may not happen if there are too many other T cells
in circulation. Because of that, if the subject's level of circulating T cells is relatively
high, s/hemay receive treatment with cyclophosphamide (Cytoxan) and fludarabine (chemotherapy
drugs) before the T cells. If the subject is already receiving chemotherapy, this may not be
needed.

The subject will be given an injection of cells into the vein through an IV at the assigned
dose. The injection will take up to 10 minutes. The research staff will follow the subject in
the clinic after the injection for up to 4 hours. If after a 4-6 week evaluation period after
the infusion, the subject seems to be experiencing a benefit (confirmed by radiological
studies, physical exam and/or symptoms), s/he may be able to receive up to 5 additional doses
of the T cells. These additional infusions would be at least 4-6 weeks apart and at the same
dose level received the first time or a lower dose.

There will be medical tests during and after treatment. To learn more about the way the CD19
chimeric receptor-T cells are working and how long they last in the body, extra blood will be
drawn.

Inclusion Criteria:

PROCUREMENT

- Group A: CD19+ B-ALL undergoing allogeneic HSCT or Group B: CD19+ B cell CLL or NHL
undergoing allogeneic HSCT

- Life expectancy of ≥12 weeks.

- Patient has an appropriate donor identified for hematopoietic stem cell
transplantation

TREATMENT

- Any patient regardless of sex or age with CD19+ B-ALL undergoing allogeneic HSCT
(Group A) OR any patient regardless of sex or age with CD19+ B-CLL or NHL undergoing
allogeneic HSCT (Group B)

- Residual disease at the time of transplant (bulky or minimal) or post transplant
relapse as evidenced by PCR positivity, specific cytogenetic abnormalities, an
abnormal population on flow cytometry or increased blasts on bone marrow biopsy or in
the peripheral blood. MRD will be defined as detection in blood or marrow of any of
the following:

- Any leukemia specific marker (such as t(9:22) or t(4:11)) documented in the
patient's leukemia cells pre transplant on a post transplant evaluation.

- An immune globulin rearrangement known to be a disease marker for this patient
post transplant.

- A leukemia specific phenotype post transplant at a level of ≥ 0.01%

- Mixed donor chimerism (any level)

- Life expectancy ≥ 6 weeks

- Karnofsky/Lansky score ≥ 50%.

- Bilirubin ≤ 2 times the upper limit of normal.

- AST ≤ 3 times the upper limit of normal.

- Estimated GFR > 50 mL/min

- Hgb ≥ 7.0 (can be a transfused value)

- Pulse oximetry of > 90% on room air

- Sexually active patients must be willing to utilize one of the more effective birth
control methods during the study and for 6 months after ATL infusion. The male partner
should use a condom.

- Available allogeneic activated peripheral blood T cell products with >=15% expression
of CD19.CAR-CD28ζ determined by flow cytometry (cell dose is based on total cell
numbers and not individual antileukemic cell numbers).

- No other investigational antitumor therapy for one month prior to entry in this study.

- Patients or legal guardians must sign an informed consent.

Exclusion Criteria:

- Severe intercurrent infection.

- Evidence of GVHD > grade II.

- Pregnant or lactating.

- History of hypersensitivity reactions to murine protein-containing products.

- Currently taking corticosteroids (>0.5 mg/kg/day prednisone or equivalent) for therapy
of GVHD.