Bendamustine Hydrochloride and Idarubicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia or Myelodysplastic Syndrome

PRIMARY OBJECTIVES:

I. The maximum tolerated dose (MTD) that is associated with a complete remission (CR) rate
of at least 40%, and a rate of grade 3-4 extramedullary toxicity < 30% in patients aged 50
or older with previously untreated AML or high-risk MDS.

SECONDARY OBJECTIVES:

I. The disease-free survival (DFS), and overall survival (OS) after therapy at each level of
the dosing strategy.

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

Patients receive bendamustine hydrochloride intravenously (IV) on days 1-5 and idarubicin IV
on days 1 and 2. Treatment repeats every 28 days for up to 3 courses in the absence of
disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and
then annually thereafter for 3 years.

Inclusion Criteria:

- Diagnosis of untreated AML or MDS with 10-19% marrow blasts; patients may be enrolled
if they received prior treatment with demethylating agents specifically for the
purpose of treating MDS or if they have received a single dose of cytarabine for the
control of symptoms related to AML

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

- Serum creatinine =< 2.0 mg/dL; if serum creatinine > 2.0 mg/dL, then the estimated
glomerular filtration rate (GFR) must be > 50 mL/min/1.73 m^2 as calculated by the
Modification of Diet in Renal Disease equation

- Serum bilirubin =< 1.5 x upper limit of normal (ULN)

- Aspartate transaminase (AST)/alanine transaminase (ALT) =< 2.5 x ULN

- Alkaline phosphatase =< 2.5 x ULN

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

- Males should be willing to use an effective contraceptive method during the study and
for a minimum of 6 months after study treatment

- Women must be postmenopausal or must be willing to use an acceptable method of
contraception to avoid pregnancy for the entire period of the study and for at least
3 months after the study; a postmenopausal woman is defined as a woman who has
experienced amenorrhea > 12 consecutive months or a woman on hormone replacement
therapy with documented follicle-stimulating hormone (FSH) level > 35 mIU/mL; for
patients in whom menopausal state is in question, a negative pregnancy test will be
required prior to enrollment

Exclusion Criteria:

- Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as
specified in the protocol

- Use of investigational agents within 30 days or any anticancer therapy within 2 weeks
before study entry with the exception of hydroxyurea or single-dose cytarabine;
subjects who are enrolled with high risk MDS (specifically) may have prior treatment
with drugs in the class called "demethylating agents"; examples of these drugs
include 5-azacytidine (azacitidine) and 5-azadeoxycytidine (decitabine), and may
include approved or experimental drugs not currently used, which fall into this class
and may be developed in the future; the patient must have recovered from all acute
toxicities from any previous therapy

- 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)

- Pregnant or lactating patients

- Any 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

- Known hypersensitivity to bendamustine (bendamustine hydrochloride) or idarubicin

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

- Have had a diagnosis of another malignancy, unless the patient has been disease-free
for at least 3 years following the completion of curative intent therapy

- Other circumstances in which patients with prior malignancies are not excluded,
include the following:

- Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical
intraepithelial neoplasia, regardless of the disease-free duration, if
definitive treatment for the condition has been completed

- Patients with organ-confined prostate cancer with no evidence of recurrent or
progressive disease based on prostate-specific antigen (PSA) values if hormonal
therapy has been initiated, or a radical prostatectomy or definitive
radiotherapy has been performed

- Concurrent hormonal therapy is allowed