Phase II Study of Decitabine and Cytarabine for Older Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

Primary objective: To determine the efficacy of an induction regimen using decitabine as an
epigenetic primer followed by cytarabine in the treatment of older patients with newly
diagnosed Acute myeloid leukemia (AML).

Primary endpoint:

Complete remission rates

Secondary objective: To determine the safety of an induction regimen of decitabine followed
by cytarabine in the treatment of older patients with newly diagnosed AML, evaluate survival
and identify potential predictive factors for response to treatment

Secondary endpoints:

- Treatment related toxicities

- 4 and 8 week mortality

- Overall survival

- Relapse-free survival

- Predictive factors for response to treatment

- Quality of Life measures including self reported symptoms and assessment of sleep
patterns

Treatment administration

Induction therapy Eligible patients will be treated with induction therapy (decitabine +
cytarabine) at the University of Pittsburgh Cancer Center inpatient leukemia service at
Shadyside Hospital. Patients will receive decitabine 20mg/m2 in 100mL normal saline (NS)
intravenously (IV) over 1 hour daily for five days, followed by cytarabine 100mg/m2 in 1000
mL normal saline (NS) as a continuous IV infusion over 24 hours for 5 days. Treatment should
be discontinued or delayed for any of the following during the treatment period: a rise in
serum creatinine > 2x patient baseline or upper limit of normal (whichever is higher) unless
there is an identifiable reversible etiology, or ALT, AST or total bilirubin > 5x upper limit
of normal, and should be held until resolution below these parameters. There are no
parameters for dose reduction.

Patients who have persistent disease on post-treatment bone marrow aspirate and biopsy, will
undergo a repeat cycle of induction with decitabine followed by cytarabine as outlined above.

Supportive care including blood product transfusions, antiemetic medications antiviral and
antifungal medications, or empiric antibiotics may be used at the clinical discretion of the
provider.

Maintenance therapy Patients in complete response (CR) will proceed to decitabine maintenance
therapy, where each treatment will be decitabine 20mg/m2 in 100mL normal saline (NS)
intravenously (IV) over 1 hour daily for five days administered in the outpatient setting.
Maintenance treatments will be continued until disease relapse. Maintenance treatments can be
administered as an outpatient at the Hillman Cancer Center, or at a University of Pittsburgh
Medical Center (UPMC) facility that is able to administer chemotherapy under the supervision
of an Oncologist

Evaluations during maintenance Phase:

During maintenance therapy, complete blood count (CBC) w/ diff/platelets, CMP (Na, K, Cl,
carbon dioxide (CO2), glucose, blood urea nitrogen (BUN), Cr, Ca, Total Protein, Albumin,
AST, ALT, Alk Phos, Total Bilirubin) will be checked each cycle on day 14 [+/- 4 days].

Within 7 days of start of new cycle, study visits will include physical exam, adverse events
assessment, CBC and comprehensive metabolic panel (CMP).

Maintenance cycles will be 28 days [+/- 7 days]. Cycles can be held up to 4 weeks [28 days].
For start of new cycle, any grade 3 or 4 non-hematologic toxicity possibly, probably or
definitely related to decitabine therapy must resolve to grade 2 or baseline.

In addition the following lab parameters must be met to start a new cycle of maintenance:

Absolute Neutrophil Count (ANC) > or = 1000/mm3 Platelets >/= 50,000/mm3 AST or ALT < 2 x
Uppler Limit of Normal (ULN) Total billirubin < 2 x ULN Serum creatinine < 2x patient
baseline or upper limit of normal (whichever is higher)

[If lab parameters are not met for start of cycle, these labs will be checked a minimum of
once per week]. If start of new cycle is held for more than 4 weeks [28 days], the subject
will be off treatment.

Other reasons for delay in treatment should be discussed with the Principal Investigator.