Chemotherapy in Treating Patients With Myelodysplastic Syndrome Before Donor Stem Cell Transplant

PRIMARY OBJECTIVES:

I. To determine the effect of induction chemotherapy (IC) (intensive acute myeloid leukemia
[AML]-like therapy), versus less intensive hypomethylating agents (HMA) as initial therapy,
on failure-free survival.

SECONDARY OBJECTIVES:

I. Determine if IC (intensive AML-like therapy) in comparison to HMA as initial therapy, will
affect transplantation frequency and quality of life.

II. Conduct exploratory analysis of post-HCT outcomes (overall survival, and relapse).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive decitabine or azacitidine intravenously (IV) or subcutaneously (SC)
for 7 days. Treatment repeats every 28 days for 4 courses of decitabine or 6 courses of
azacitidine in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive induction-like chemotherapy per standard of care or per experimental
protocol. This study does not require a specific chemotherapy regimen for Arm B.

After completion of study treatment, patients are followed up for 18 months.

Inclusion Criteria:

- Diagnosis of de novo or secondary myelodysplastic syndrome (MDS), including chronic
myelomonocytic leukemia, as defined by the 2008 World Health Organization
classification system

- Patients must have measurable disease requiring cytoreduction, defined as a bone
marrow myeloblast count >= 5% and < 20% on morphologic examination or by flow
cytometry in cases in which adequate morphologic examination is not possible

- Patients must be considered to have an acceptable risk of early mortality with
intensive chemotherapy as determined by the attending physician at the time of the
initial visit; since the specific therapy within each arm will be determined after
randomization, there is no threshold of organ dysfunction or performance status for
inclusion

- Considered a potential transplant candidate; the attending/treating physician will
determine transplant candidacy at the time of consent

- Capable of understanding the investigational nature, potential risks and benefits of
the study, and able to provide valid informed consent

Exclusion Criteria:

- A diagnosis of acute promyelocytic leukemia as defined by the 2008 World Health
Organization classification system

- Previous treatment for MDS or AML with intensive chemotherapy regimen (induction
chemotherapy) or hypomethylating agent

- Have any other severe concurrent disease, or have a history of serious organ
dysfunction or disease involving the heart, kidney, liver, or other organ system that
may place the patient at undue risk to undergo treatment

- Patients with a systemic fungal, bacterial, viral, or other infection not controlled
(defined as exhibiting ongoing signs/symptoms related to the infection and without
improvement, despite appropriate antibiotics or other treatment)

- Females who are pregnant or breastfeeding

- Fertile men and women unwilling to use contraceptive techniques during and for 12
months following treatment

- Any uncontrolled or significant concurrent disease, illness, or psychiatric disorder
that would compromise patient safety or compliance, interfere with consent, study
participation, follow up, or interpretation of study results

- Clinical evidence suggestive of central nervous system (CNS) involvement with MDS
unless a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal
fluid (CSF)