Infusion of Allogeneic CD19-Specific T Cells From Peripheral Blood

Gene Transfer:

Gene transfer involves drawing blood from a transplant donor, and then separating out the
T-cells using a machine. Researchers then perform a gene transfer to change the T-cells' DNA,
and then inject the changed T-cells into the body of the patient receiving the transplant.
This process is called a modified donor lymphocyte infusion (DLI).

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to 1 of 4
study arms, based on your age, treatment schedule, and disease status:

- Participants in Arm 1 will receive the T-cells by vein about 6-12 weeks after the stem
cell transplant. (Adults participants only)

- Participants in Arm 2 will receive the T-cells by vein if, at any point, the disease
comes back after stem cell transplant. Your doctor may decide that you need to receive
chemotherapy before you are given the T-cells, in order to clear out the T-cells that
are in your body already. This may help the infused T-cells work better. If more
chemotherapy is needed, you will sign another informed consent document, which will the
chemotherapy and its risks in detail. (Pediatric and adult participants eligible)

- Participants in Arm 3 will receive the T-cells by vein about 6-12 weeks after the stem
cell transplant. (Pediatric participants [ages 1-17] only)

- Participants in Arm 4 will be given the T-cells as a scheduled infusion or if the
disease comes back. This group is also scheduled to receive a stem cell transplant from
a mismatched family member donor. (Pediatric and adult participants eligible)

Once you have been assigned to a study arm, you will be assigned to 1 of 4 dose levels of
genetically-changed T-cells, based on when you joined this study. The first group of
participants will receive the lowest dose of T-cells, and each new group will receive a
higher dose of changed T-cells than the group before it, as long as no intolerable side
effects were seen.

Chemotherapy and HSCT:

After your donor's stem cells have been successfully collected, you will be admitted to the
hospital to receive chemotherapy and the HSCT. These procedures are not considered part of
this research study. You will discuss these procedures with a study doctor and sign an
informed consent document with specific details of the HSCT procedure and possible risks, at
another time.

The T-cell Infusion:

After the HSCT, the study chair will decide when you will be eligible for the T-cell
infusion. You must be at least 42 days past your transplant without any serious evidence of
active graft versus host disease (GVHD). GVHD occurs when donor cells attack the cells of the
person receiving the transplant.

Before the infusion, you will receive drugs to lower your risk of allergic reaction to the
T-cells. Tylenol® (acetaminophen) will be given by mouth, and Benadryl® (diphenhydramine) may
be given by mouth or by vein over a few minutes.

The T-cell infusion is given by vein, usually over 15-30 minutes. During the infusion, your
vital signs will be checked. The infusion may be given on one day, or it may be divided into
two parts at least 24 hours apart. The first part of the infusion will be a much smaller part
to ensure that you have no immediate side effects.

Before the T cell infusion, you will receive drugs to lower your risk of allergic reaction to
the T cells. Acetaminophen (Tylenol®) will be given by mouth, and diphenhydramine (Benadryl®)
will be given by vein over a few minutes.

If your cancer returns after the transplant, you may receive an additional T-cell infusion.
If you receive an additional T-cell infusion, the screening tests will be repeated. The study
doctor will discuss the results of the repeated screening tests with you. If the screening
tests show that you are not eligible to receive the additional T-cell infusion, other
treatment options will be discussed with you.

Study Tests:

Within 3 days after the T-cell infusion, and then about 1 week, 2 weeks, 4 weeks, 8 weeks, 3
months, 6 months and 12 months after the T-cell infusion, the following tests will be
performed:

- You will have a physical exam, including measurement of your height, weight, and vital
signs.

- Your medical history will be recorded.

- Blood (about 4 tablespoons each time) will be drawn for research tests to check the
level of the infused T-cells and to measure the number of B-cells and other
(non-transplanted) T-cells.

- Blood (about 4 tablespoons each time) will be drawn for routine tests and tests of your
blood chemistry, and blood sugars. During the 4 week, 8 week, 3 month, 6 month, and 12
month visits, part of this blood sample will be used for tests of certain protein
levels. During the Month 3 visit, part of this blood sample will be used to check for
HAMA immune system reactions. If you leave the study before the Month 3 visit, blood
(about 1 tablespoon) may be collected for HAMA immune system reaction testing, if
possible.

- You will have be checked for possible reactions to your treatment, including GVHD and
graft failure. Graft failure occurs when donor cells may not be able to grow and
multiply in your body. If this happens, there will be a high risk of infections and/or
bleeding. If the number of white blood cells does not get back to high enough levels
within 3 weeks after the transplant, more blood stem cells from the stem cell donor may
be given.

- You may need a skin biopsy or an endoscopy to check for GVHD and/or graft failure, as
well. To collect a skin biopsy, the biopsy area is numbed with anesthetic, and a small
amount of skin is collected using a needle or scalpel. An endoscopy is an exam where you
will be mildly sedated to allow a thin, flexible, lighted tube, called an endoscope, to
be inserted inside the esophagus, stomach, and first part of the small intestine. This
will allow the doctor to look for abnormal areas that might not be so easily seen in
x-rays.

Within 3 months after the T-cell infusion, you will have CT scans and/or a bone marrow biopsy
to check the status of the disease. An extra sample of bone marrow aspirate (about 2
teaspoons each time) will be drawn for research tests whenever a bone marrow aspirate/biopsy
is being done if possible. These samples will be used for research tests to study how your
immune system responds to the infusion of T-cells. To collect a bone marrow aspirate, an area
of the hip is numbed with anesthetic, and a small amount of bone marrow is withdrawn through
a large needle.

Length of Study:

You may continue taking part in this study for up to 3 months. You will be taken off study if
the disease gets worse, you have any infections, or intolerable side effects occur.

Your participation on this study will be over once you have completed the planned study
visits at 3 months after the T-cell infusion.

Retreatment:

If you are taken off study because the disease got worse, you may be able to enroll on study
again once the highest tolerated dose of T-cells is found. If this happens, you will follow
the same schedule for dosing and study tests as described above.

Long-Term Follow-Up:

For safety reasons, the U.S. Food and Drug Administration (FDA) requires that patients who
receive infusions of stem cells treated with a gene transfer procedure must have long-term
follow-up for at least 15 years after receiving the gene transfer.

This is an investigational study. The gene transfer or DLI (infusion with genetically-changed
T-cells) are not commercially available or FDA approved for use in this type of disease.
Their use in this study is considered investigational. The donor's leukapheresis procedure to
collect cells for the manufacture of changed T-cells will be provided at no cost to you while
you are on study.

Up to 140 patients (and up to 140 donors) will take part in this study. All will be enrolled
at MD Anderson.

Inclusion Criteria:

1. Patients with a history of CD19+ lymphoid malignancies that are primary refractory to
treatment (do not achieve complete remission after first course of therapy) or are
beyond first remission including second or greater remission or active disease.
Patients in first remission are eligible if they are considered high risk, defined as
any of the following detected at any time:1) Acute Lymphoblastic Leukemia (ALL) with
translocations 9;22 or 4;11, hypodiploidy, complex karyotype, secondary leukemia
developing after cytotoxic drug exposure,and/or evidence of minimal residual disease,
2) acute biphenotypic leukemia, or 3) double hit nonHodgkin's lymphoma. Non-Hodgkin's
Lymphoma (NHL) in second or third complete remission, or relapse (including relapse
post autologous hematopoietic stem cell transplant). Double hit lymphomas in first
remission or more advanced disease. Small Lymphocytic Lymphoma (SLL), or Chronic
Lymphocytic Leukemia (CLL) with progressive disease following standard therapy.

2. Age 1 to 65 years old.

3. Lansky performance score >/= 60% for patients performance 0-1 or Karnofsky greater than or equal to 80% for patients > 16 years of
age.

4. Patient or patient's legal representative, parent(s) or guardian able to provide
written informed consent.

5. Patient or patient's legal representative, parent(s) or guardian able to provide
written informed consent for the long-term follow-up gene therapy study.

6. Patient is planning to receive or has received an HLA-identical matched family,
related haploidentical donor ( allogeneic HSCT.

Exclusion Criteria:

1. Patients with known allergy to bovine or murine products.

2. Active grade 2-4 acute GVHD at time of DLI.

3. Systemic corticosteroid use within 72 hours of DLI unless required for physiologic
replacement.

4. Less than 80% donor chimerism from peripheral blood within 30 days of DLI
administration, if T cells are made from allogeneic donor.

5. Experiencing any new Grade >2 (CTC version 4) adverse neurologic, pulmonary, cardiac,
gastrointestinal, renal or hepatic (excluding albumin) event within 24 hours prior to
DLI.

6. Currently using an investigational agent at time of DLI.

7. Active infection defined as positive culture, if available, for bacteria, fungus, or
virus within a 3-day period prior to DLI and/or fever greater than 38°C within 24
hours prior to DLI.

8. Positive beta HCG in female of child-bearing potential defined as not post menopausal
for 12 months or absence of previous surgical sterilization.

9. Active CNS disease in patient with history of CNS malignancy.

10. Positive serology for HIV.