Laboratory-Treated T Cells in Treating Patients With High-Risk Relapsed Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia Previously Treated With Donor Stem Cell Transplant

PRIMARY OBJECTIVES:

I. Determine the safety and potential toxicities associated with treating patients with high
risk or relapsed AML, MDS, and CML after allogeneic hematopoietic cell transplantation (HCT)
by adoptive transfer of virus-specific cluster of differentiation (CD)8 T cells
genetically-modified to express a high affinity Wilms tumor 1 (WT1)-specific T cell receptor
(TCR).

II. Determine the anti-leukemic activity associated with treating patients with relapsed AML,
MDS and CML after allogeneic HCT by adoptive transfer of virus-specific CD8 T cells
genetically-modified to express a high affinity WT1-specific T cell receptor (TCR).

SECONDARY OBJECTIVES:

I. Determine the in vivo persistence of transferred T cells and ability to migrate to and
accumulate in bone marrow.

II. Determine the maintenance of TCR expression and function of transduced T cells.

OUTLINE: Patients are assigned to 1 of 2 treatment arms.

ARM I: Patients with no evidence of leukemia post-HCT receive WT1-sensitized T cells
intravenously (IV) over 45 minutes (or longer for patients who are 15-30 kg) on days 0 and 14
and aldesleukin subcutaneously (SC) twice daily (BID) on days 14-28.

ARM II: Patients with evidence of AML (minimal residual disease or overt relapse) post-HCT
receive cyclophosphamide IV and fludarabine phosphate IV daily on days -4 to -2. Patients
also receive WT1-sensitized T cells IV over 45 minutes (or longer for patients who are 15-30
kg) on days 0 and 21 and aldesleukin SC BID on days 14-28.

After completion of study treatment, patients are followed up weekly for 4 weeks, at weeks 6
and 8, at 3, 6, 12 months, and then annually for up to 15 years.

Inclusion Criteria:

- Patients must express HLA-A*0201

- Patients who are currently undergoing or who previously underwent matched allogeneic
HCT for:

- AML: Prospective enrollment will now be limited to patients with relapsed disease
(overt relapse or minimal residual disease) at any time post allogeneic HCT

- MDS will no longer be a criterion for eligibility

- CML will no longer be a criterion for eligibility

- Patients must have an HLA-matched donor of hematopoietic stem cells (related or
unrelated)

- Patients must be able to provide blood and bone marrow samples and undergo the
procedures required for this protocol

- Patients must be >= 15 kg

- Patients must be able to give informed consent; parent or legal representative will be
asked to consent for patients younger than 18 year old

- DONOR: Patient and donor (related or unrelated) must be HLA-matched and express
HLA-A*0201

- DONOR: Donor must be Epstein-Barr virus (EBV) or cytomegalovirus (CMV) seropositive

- DONOR: Donor must be age 18 or older

- DONOR: In good general health

- DONOR: Able to give informed consent

Exclusion Criteria:

- Central nervous system (CNS) tumor refractory to intrathecal chemotherapy and/or
cranio-spinal radiation

- In patients whose leukemic cells are available for evaluation, the expression of WT1
in the patient's bone marrow will be determined; if WT1 expression in the patient's
bone marrow is not highly expressed by polymerase chain reaction (PCR), the patient
will be excluded from the study; patients with no evaluable leukemia will be eligible
for enrollment based on the high frequency of positive leukemias (> 90%), and leukemia
will be evaluated for WT1 expression if recurrence is detected

- Human immunodeficiency virus (HIV) seropositive; testing for HIV should be within 6
months of enrollment

- Medical or psychological conditions that would make the patient unsuitable candidate
for cell therapy at the discretion of the principal investigator (PI)

- Pregnancy or breast-feeding; women of childbearing potential must have a negative
serum or urine beta-human chorionic gonadotropin (B-hCG) pregnancy test result within
14 days before the first dose of WT1-specific T cell infusion; woman of
non-childbearing potential will be defined as being postmenopausal greater than one
year or who have had a bilateral tubal ligation or hysterectomy; all recipients of
WT1-specific T cells will be counseled to use effective birth control during
participation in this study and for 12 months after the last T cell infusion

- DONOR: Less than 18 years old

- DONOR: Active infectious hepatitis

- DONOR: HIV or human T-lymphotropic virus (HTLV) seropositive

- DONOR: Pregnancy or nursing

- DONOR: Significant medical conditions (e.g. immunosuppressive therapy) that would make
the donor an unsuitable T cell donor

- DONOR: Unable to give informed consent