Ruxolitinib Phosphate and Decitabine in Treating Patients With Relapsed or Refractory or Post Myeloproliferative Acute Myeloid Leukemia

PRIMARY OBJECTIVES:

I. To determine the tolerability of the combination of decitabine and ruxolitinib phosphate
(ruxolitinib [DI]) in patients with leukemia. (Phase I) II. To determine the efficacy of
ruxolitinib in increasing and prolonging response induced by decitabine alone in patients
with post myeloproliferative neoplasm acute myeloid leukemia (AML) (post MPN-AML)
alternatively referred to as (myeloproliferative neoplasm - blast phase; MPN-BP). (Compared
to historical response rate with decitabine alone) (Phase II)

SECONDARY OBJECTIVES:

I. To compare whether there is a difference in response rate patients with post-MPN AML with
janus kinase 2 (JAK2) mutations and patients without JAK2 mutations.

OUTLINE: This is a phase I, dose-escalation study of ruxolitinib phosphate followed by a
phase II study.

Patients receive ruxolitinib phosphate orally (PO) twice daily (BID) on days 1-28 and
decitabine intravenously (IV) over 1-2 hours on days 1-5. Treatment repeats every 4-6 weeks
for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Inclusion Criteria:

- Diagnosis of AML (World Health Organization [WHO] classification definition of >= to
20% blasts)

- In the phase I portion of the study all patients with relapsed or refractory AML are
eligible; for the Phase II portion of the study, patients must have AML progressing
from prior MPN (MPN-BP) or have myelodysplastic syndrome (MDS)/MPN with more than 20%
blasts; temporary prior measures to control blood counts, such as apheresis or Hydrea
are allowed; patients with newly diagnosed or previously treated disease are eligible
as long as prior therapy does not include hypomethylating agents; prior therapy for
ruxolitinib for MPN is allowed

- Serum biochemical values with the following limits unless considered due to leukemia:

- Creatinine =< 1.5 mg/dl

- Total bilirubin =< 1.5 mg/dL, unless increase is due to hemolysis or congenital
disorder

- Transaminases (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x upper limit of
normal (ULN)

- Ability to take oral medication

- Ability to understand and provide signed informed consent

- Performance status =< 3, unless directly related to disease process as determined by
the principal investigator

Exclusion Criteria:

- Any coexisting medical condition that in the judgment of the treating physician is
likely to interfere with study procedures or results including uncontrolled severe
infections, as well as uncontrolled cardiac disease, or other organ dysfunction;
patients with history of tuberculosis, human immunodeficiency virus (HIV) or hepatitis
B and C are excluded

- Nursing women, women of childbearing potential with positive blood pregnancy test
within 30 days of study start, or women of childbearing potential who are not willing
to maintain adequate contraception (such as birth control pills, intrauterine device
[IUD], diaphragm, abstinence, or condoms by their partner) over the entire course of
the study

- Incomplete recovery from any prior surgical procedures or had surgery within 4 weeks
prior to study entry, excluding the placement of vascular access

- Active clinically serious and uncontrolled infection