Decitabine, Donor Natural Killer Cells, and Aldesleukin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

PRIMARY OBJECTIVES:

I. To determine the feasibility and safety of decitabine followed by natural killer (NK)
cells and IL-2 (Interleukin).

II. To define the specific toxicities and the dose limiting toxicity (DLT) of decitabine plus
NK cells and IL-2.

III. To determine the feasibility and safety of manufacturing processes for NK cells.

SECONDARY OBJECTIVES:

I. To determine the overall response rate (ORR). II. To determine the rate of complete
remission (CR) to this regimen of decitabine plus NK cells and IL-2 (interleukin) in acute
myeloid leukemia (AML).

TERTIARY OBJECTIVES:

I. To correlate the biological activity of decitabine as in upregulating ligands that mediate
susceptibility to NK mediated cytotoxicity.

II. To characterize the biological activity of infused NK cells and persistence as defined by
NK chimerism.

III. To evaluate if decitabine has immunosuppressive properties or modulates changes in
endogenous cytokines in patients.

OUTLINE:

Patients receive decitabine intravenously (IV) over 60 minutes on days -4 to 0 and undergo
infusion of allogeneic NK cells on day 0. Beginning 1 hour after infusion allogeneic NK
cells, patients also receive aldesleukin subcutaneously (SC) every other day for 6 doses.

After completion of study treatment, patients are followed up for 30 days.

Inclusion Criteria:

- Patients with relapsed or refractory AML

- Patients without a response after two cycles of decitabine

- Patients with primary refractory AML (persistent disease after standard induction
with 7+3) or relapsed AML

- Patients who have relapsed post-allogeneic transplant

- Patients with secondary AML or therapy related disease (t-AML) are eligible; patients
who received decitabine or 5-azacytidine as prior treatment for myelodysplastic
syndrome (MDS) remain eligible

- Patients with central nervous system (CNS) leukemia are eligible as long as they have
received treatment and most recent cerebrospinal fluid (CSF) analysis is negative for
leukemia

- If the patient has co-morbid medical illness, life expectancy attributed to the
comorbid illness must be greater than 6 months

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Total bilirubin < 2.0 mg/dL

- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) <
2.5 X institutional upper limit of normal

- Creatinine < 2.0 mg/dL

- New York Heart Association (NYHA) congestive heart failure (CHF) class II or better

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and for
the duration of study participation; if the patient does not agree, the patient is not
eligible; should a woman become pregnant or suspect she is pregnant while
participating in this study, she should inform her treating physician immediately

- Ability to understand and willingness to sign the written informed consent document

- Human immunodeficiency virus (HIV) infection without acquired immune deficiency
syndrome (AIDS)-defining criteria are eligible

- DONOR: Donors must be human leukocyte antigen (HLA)-haploidentical first-degree
relatives of the patient; eligible donors include biological parents, siblings or
half-siblings, or children

- DONOR: Donor must be in general good health and eligible for apheresis as determined
by the medical provider

- DONOR: HLA-haploidentical donor/recipient match by at least class I serologic typing
at the HLA-A and B loci

- DONOR: Willing and able to provide informed consent

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study

- Patients receiving any other investigational agents or patients that have received
other investigational agents within 14 days of enrollment

- Patients with history of allergic reactions attributed to compounds of similar
chemical or biologic composition to decitabine that are not easily managed

- Uncontrolled intercurrent illness including, but not limited to, symptomatic
congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, or
psychiatric illness/social situations that would limit compliance with study
requirements; as infection is a common feature of AML, patients with active infection
are permitted to enroll provided that the infection is under control

- Patients with serious medical or psychiatric illness likely to interfere with
participation in this clinical study

- Pregnant women or women who are breastfeeding are excluded from this study;
confirmation that the subject is not pregnant must be established by a negative serum
B-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during
screening; pregnancy testing is not required for post-menopausal or surgically
sterilized women

- Patients with metastatic malignant solid tumors who received treatment in the past 6
months are excluded

- DONOR: Pregnancy

- DONOR: HIV