DEC-205/NY-ESO-1 Fusion Protein CDX-1401and Decitabine in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia

PRIMARY OBJECTIVES:

I. Evaluate the safety of Anti-DEC-205-NY-ESOI (CDX-1401) fusion protein (DEC-205/NY-ESO-1
fusion protein CDX-1401) given in combination with decitabine 20 mg/m^2 intravenously.

SECONDARY OBJECTIVES:

I. To evaluate NY-ESO-1 specific cellular and humoral immunity by determination of NY-ESO-1
specific antibody, and T-cell clones following standard treatment with 5-aza-2'-deoxycytidine
(decitabine) in conjunction with immune sensitization with Anti-DEC 205-NY-ESO-I fusion
protein (CDX-1401).

II. To determine the impact of decitabine treatment on peripheral blood cells from patients
treated in this manner on NY-ESO-1 target gene expression, NY-ESO protein expression,
NY-ESO-1 promoter methylation, and global deoxyribonucleic acid (DNA) methylation.

TERTIARY OBJECTIVES:

I. To record the response rate (complete response, partial response and hematological
improvement) in myelodysplastic syndrome (MDS) or low blast count acute myeloid leukemia
(AML) patients treated with the combination in order to provide descriptive characteristics.

OUTLINE:

Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 subcutaneously (SC) and
intradermally (ID) and poly-ICLC subcutaneously (SC) on days -14 and 15 of course 1 and on
day 15 for courses 2-4. Patients also receive decitabine intravenously (IV) over 1 hour on
days 1-5. Treatment repeats every 28 days for up to 4 courses in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30, 60, 90, and 180 days.

Inclusion Criteria:

- Subjects with a confirmed diagnosis of:

- International Prognostic Scoring System (IPSS) intermediate-I, interrnediate-2 or
high-risk MDS including chronic myelomonocytic leukemia (CMML) or

- Low blast count AML with =< 30% blasts previously classified as refractory anemia
with excess blasts in transformation who have not been previously treated with a
hypomethylating agent

- Patients with IPSS intermediate-1 disease with an isolated deletion of chromosome
5q must have previously failed treatment with lenalidomide

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

- Total bilirubin =< 2 x upper limit of normal (ULN)

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

- Serum creatinine =< 1.5 x ULN

- Any human leukocyte antigen (HLA) type

- Subjects of child-bearing potential must agree to use adequate contraceptive methods
(e.g., hormonal or barrier method of birth control; abstinence) prior to study entry,
for the duration of study participation, and for 6 months after the last treatment;
should a woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she should inform her treating physician immediately

- Subject or legal representative must understand the investigational nature of this
study and sign an Independent Ethics Committee/Institutional Review Board approved
written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

- Subjects with life-threatening illnesses other than MDS, uncontrolled medical
conditions or organ system dysfunction which, in the investigator's opinion, could
compromise the subject's safety, or put the study outcomes at risk

- AML associated with inv(16); t(16;16); t(8;21) or t(15;17)

- Subjects with uncontrolled or symptomatic arrhythmias, or any class 3 or 4 cardiac
disease as defined by the New York Heart Association functional classification

- Subjects with symptomatic central nervous system (CNS) disease which is not adequately
controlled

- Subjects who have received prior radiation therapy for extramedullary disease within 2
weeks of first dose

- Subjects with human immunodeficiency virus (HIV) or active infection with hepatitis C
virus (HCV) or hepatitis B virus (HBV)

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Subjects who are being treated with systemic corticosteroids

- Subjects who have hypersensitivity to decitabine

- History of auto-immune disease (e.g. thyroiditis, lupus) except vitiligo

- Pregnant or nursing female subjects

- Unwilling or unable to follow protocol requirements

- Any condition which in the investigator's opinion deems the subject an unsuitable
candidate to receive study drug

- Received an investigational agent within 30 days prior to enrollment

- Active malignancy with the exception of basal cell carcinoma, non-melanoma skin
cancer, cervical carcinoma-in-situ; other prior malignancies in remission for less
than 1 year

- Subjects previously treated with an allogeneic stem cell transplant