Administration of Donor MultiTAA-Specific T Cells for ALL

To make donor-derived multiTAA-specific T cells, the investigators will collect blood from
the patient's stem cell donor, and mix the donor's T cells with small pieces of the tumor
proteins WT1, PRAME and Survivin. These protein fragments stimulate the donor T cells to grow
and react against these proteins in such a way that they will recognize and kill cancer cells
that express these proteins. Once sufficient numbers of multiTAA-specific T cells have been
made, the investigators test them to make sure they target the patient's cancer cells, but
not their normal healthy cells.

The multiTAA-specific T cells will be administered as a single intravenous (IV) infusion over
10 minutes. The patient's cancer will be assessed within 4 weeks prior to the T cell
infusion, at 4-6 weeks, and again at 8-12 weeks after the infusion. If at least 4 weeks after
the infusion there is no change or a reduction in the number of cancer cells measured in the
bone marrow, or a decline in cancer-specific markers in the blood, patients may receive up to
six (6) additional doses of the T cells at least 4 weeks apart. All of the treatments will be
given by the Center for Cell and Gene Therapy at Houston Methodist Hospital or Texas
Children's Hospital.

For at least 4 weeks after the infusion, patients may not receive any other anti-cancer
treatments, such as radiation therapy or chemotherapy, with the exception of drugs like
dasatinib. Patients who do receive any other therapies will be taken off treatment, and will
not be able to receive additional doses of T cells.

This is a dose escalation study, which means that at the beginning, patients will be started
on the lowest dose (1 of 3 different levels) of T cells. Once that dose level proves safe,
the next group of patients will be started at the next highest dose. This process will
continue until all 3 dose levels have been studied. If side-effects are too severe, the dose
will be lowered or the T cell injections will be stopped.

Before being treated, patients will undergo a series of standard medical tests:

- Physical exam.

- Blood tests to measure blood cells, kidney and liver function.

- Measurement of ALL (done by a bone marrow biopsy or blood tests).

- Pregnancy test, if patient is a female who can have children.

Patients will undergo standard medical tests both during the T cell infusions and after:

- Blood tests to measure blood cells, kidney and liver function.

- Measurement of disease 4-6 weeks and 8-12 weeks after the T cell infusion (done by bone
marrow biopsy or blood tests).

Active participation in this study will last for approximately one (1) year. If the patient
receives additional doses of the T cells as described above, their active participation will
last until one (1) year after the last dose of T cells. We will then contact the patient once
a year for up to 4 additional years (total of 5 years follow-up) in order to evaluate disease
response long-term.

Inclusion Criteria:

Only patients who receive infusions in the integrated Cell and Gene Therapy (CAGT)
Transplant program at Texas Children's Hospital (TCH) or Houston Methodist Hospital (HMH)
are eligible for this study.

1. Patients will be eligible to receive donor-derived multiTAA-specific T cells following
any type of allogeneic HSCT as:

(i) Adjuvant therapy for ALL (Group A), or (ii) Treatment for relapsed/residual ALL
disease (Group B)

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

(i) Any leukemia-specific marker (such as t(12;21); t(9;22) or t(4;11)) documented in
the patient's leukemia cells pre-transplant on a post-transplant evaluation.

(ii) A leukemia-specific phenotype (e.g. expression of markers including CD10 and/or
CD19 or CD3 and/or CD4 or CD8) post-transplant at a level greater than or equal to
0.01%.

(iii) Mixed donor chimerism (greater than 20%).

2. Life expectancy greater than or equal to 6 weeks.

3. Karnofsky/Lansky score of greater than or equal to 50.

4. Patient or parent/guardian capable of providing informed consent.

5. Bilirubin less than or equal to 2X upper limit of normal.

6. AST less than or equal to 3X upper limit of normal.

7. Serum creatinine less than or equal to 2X upper limit of normal.

8. Hgb greater than 8.0 g/dL (can be transfused).

9. Pulse oximetry of greater than 90% on room air.

10. Sexually active patients must be willing to utilize one of the more effective birth
control methods for 6 months after the ATL infusion. Male partner should use a condom.

11. Available donor-derived multiTAA-specific T cell line.

12. No other investigational anti-neoplastic therapy for one month prior to entry in this
study.

Exclusion Criteria:

1. Patients receiving ATG or Campath within 28 days of infusion.

2. Patients receiving a Donor Lymphocyte Infusion (DLI) within 4 weeks of planned T cell
infusion.

3. Less than 30 days post-allogeneic stem cell transplant.

4. Severe intercurrent infection.

5. Evidence of GVHD greater than Grade II.

6. Pregnant or lactating.

7. Currently taking corticosteroids (greater than 0.5 mg/kg/day prednisone or
equivalent).

Donor Eligibility:

Donors for allogeneic (i.e. HLA matched or mismatched related or unrelated) stem cell
transplants who have fulfilled eligibility for and consented to stem cell donation as per
the stem cell transplant program's standard operating procedures. Subjects must be at least
12 kg or 24 pounds to be eligible for stem cell donation. The stem cell donor will have
already been selected by the primary Bone Marrow Transplant attending according to CAGT
SOPs for Donor Evaluation, Donor Selection, and Donor Deferral. If a donor has been chosen
for the transplant based on urgent medical need, that same donor will also be used for T
cell generation, provided that there are no new reasons for ineligibility since the stem
cell collection. In this study, the subject's hematopoietic stem cell donor will also be
the donor for the T cells.