AML Therapy With Irradiated Allogeneic Cells

PRIMARY OBJECTIVES:

I. Toxicity of haploidentical allogeneic cellular therapy in patients in complete remission
(CR) (or CR with incomplete platelet recovery [CRp]) after induction chemotherapy with
fludarabine (fludarabine phosphate)-cytarabine.

II. Efficacy of haploidentical allogeneic cellular therapy in patients in CR (or CRp) after
induction chemotherapy with fludarabine-cytarabine (remission rates at 6, 12, 18, 24 months).

SECONDARY OBJECTIVES:

I. Immunologic parameters before and after haploidentical therapy: host anti-leukemia T
cells; host regulatory T cells.

OUTLINE:

INDUCTION CHEMOTHERAPY: Patients receive fludarabine phosphate intravenously (IV) over 1 hour
once daily (QD) for 5 days and cytarabine IV over 4 hours for 5 days. Treatment may continue
for 1 or 2 courses at the discretion of the treating physician.

ALLOGENEIC CELLULAR THERAPY: Patients undergo irradiated donor lymphocyte infusion (DLI) of 3
x 10^8 cluster of differentiation (CD)3+ cells/kg at 8 weeks. Patients with stable disease
may repeat irradiated DLI every 8-12 weeks in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for up to 2 years.

Inclusion Criteria:

- Histologically proven non-M3 AML:

- Refractory/relapsed AML OR

- Initial diagnosis of AML in patient >= 60 years old

- Total bilirubin =< 1.5 times upper limit of normal (ULN) institutional limits (unless
Gilbert's disease)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 X institutional ULN

- Cardiac left ventricular ejection fraction (LVEF) >= 35%

- Serum creatinine =< 1.5 mg/dl

- Any organ dysfunction thought to be secondary to disease will be considered separately
and the patient will be included at the investigators discretion

- Patients must give informed consent

- Eastern Cooperative Oncology Group (ECOG) performance status =< 3

- Must have a potential haploidentical donor (parent, sibling, child)

- A patient is eligible for second enrollment (allo-cellular therapy) if all of the
following inclusion criteria are met:

- Patient must have documented CR or CRp after 1 or 2 cycles of fludarabine + cytarabine

- Patient must not be a candidate for an allo-hematopoietic stem cell transplant (HSCT)

- Patient must have a partially (>= 3/6 class I antigen) human leukocyte antigen
(HLA)-matched (by serology or low resolution deoxyribonucleic acid [DNA] testing)
relative able to serve as a donor

- Patients must not have active uncontrolled infections, other medical or
psychological/social conditions that might increase the likelihood of patient adverse
effects or poor outcomes

- Total bilirubin < 1.5 times upper limit of normal (ULN) institutional limits (unless
Gilbert's disease)

- AST(SGOT)/ALT(SGPT) =< 2.5 X institutional ULN

- Serum creatinine < 2.0 mg/dl

- ECOG performance status =< 2

- DONOR: donor must be related to patient and be partially (>= 3/6 antigen) HLA-matched

- DONOR: donor must meet all New Brunswick Affiliated Hospitals (NBAH) requirements for
hematopoietic stem cell donation, including:

- DONOR: age >= 18 years old

- DONOR: white blood cells (WBC) 4.0-10.0 x 10^3/mm^3

- DONOR: platelet count 150,000 to 440,000/mm^3

- DONOR: hemoglobin/hematocrit; 12.5-18 g/dl, 38 to 54%

- DONOR: not pregnant or lactating

- DONOR: not human immunodeficiency virus (HIV)-1, HIV-2, hepatitis C virus (HCV),
hepatitis B core or human T-lymphotropic virus (HTLV)-I/II seropositive; hepatitis B
surface antigen (HB S ag) (-); meet other infectious disease screening criteria
utilized by NBAH Blood Center

- DONOR: no uncontrolled infections, other medical or psychological/social conditions,
or medications that might increase the likelihood of patient or donor adverse effects
or poor outcomes

- DONOR: meet other blood bank criteria for blood product donation (as determined by
NBAH Blood Center screening history and laboratory studies)

Exclusion Criteria:

- History of current or prior medical problems that the investigator feels will prevent
administration of therapy or assessment of response due to excess toxicity

- Patients with known active central nervous system (CNS) leukemia will be excluded from
this clinical study

- Known HIV-positive patients are excluded from the study

- Patients may not be pregnant or breast feeding