Decitabine and Cytarabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia, High Risk Myelodysplastic Syndrome, or Myeloproliferative Neoplasm

PRIMARY OBJECTIVES:

I. Examine whether a combination of decitabine given for 10 days (days 1-10), rather than the
usual 5 days, plus "standard dose cytarabine (ara-C) (100 mg/m^2 daily days 1-7) might
improve 6-month survival probability from the historical 65% to 80% in patients age >= 60
with newly diagnosed acute myeloid leukemia (AML).

II. Test whether this combination might maintain complete response (CR) rate at our historic
45% in these patients.

III. Study factors that lead physicians to escalate or maintain ara-C doses in those patients
who have had an "intermediate response" short of CR to the first 2 cycles of the combination.

IV. While maintaining awareness of confounding covariates, examine the effect of such dose
escalation on CR rate.

OUTLINE:

Patients receive decitabine intravenously (IV) daily on days 1-10 and cytarabine IV once
daily (QD) on days 1-7. Treatment repeats every 28-35 days for 2 courses in the absence of
disease progression or unacceptable toxicity. After course 3, patients achieving remission
will receive 1-2 more courses of therapy at the same dose. Patients in remission with
significant side effects will receive decitabine and cytarabine at decreased doses. Patients
not achieving remission will not receive any more treatment.

After completion of study treatment, patients are followed up for 6 months and then
periodically.

Inclusion Criteria:

- Newly-diagnosed AML by World Health Organization (WHO) criteria (>= 20% myeloid blasts
by morphology in either blood or marrow)

- High-risk myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN)
including chronic myelomonocytic leukemia 2 (CMML2) as defined by 10-19% myeloid
blasts in either blood or marrow

- Patients may have received azacitidine, decitabine, or lenalidomide but no "cytotoxic
therapy" such as ara-C or anthracyclines; data suggest that failure to respond to
azacitidine reduces probability of response to 3+7; hence in the interest of having a
relatively homogeneous population, while patients who have received and failed
azacitidine or decitabine will be eligible for this study, they will be analyzed
separately from patients who have not received these drugs

- Treatment related mortality (TRM) score < 22.9; patients with TRM scores > 13.1, in
whom the risk of death within 28 days of beginning induction therapy has averaged 41%,
will preferentially be placed on protocol 2642

- Provision of written informed consent

- Note, unlike pharmaceutical company sponsored protocols eligibility is not conditioned
on bilirubin, creatinine, or absence of other malignancy within the past 2-3 years;
the TRM score incorporates creatinine and thus a high creatinine can in principle be
offset by favorable values for the other covariates in the TRM score; bilirubin was
not a covariate in the TRM; furthermore, in the doses we are using, dose adjustment of
decitabine or ara-C is not indicated in the presence of renal or hepatic
abnormalities; our broad eligibility criteria may increase the likelihood that our
results will be generalizable; the inability to reproduce results of early phase AML
studies has been a problem in the past