Clofarabine and Cytarabine in Treating Older Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes That Have Relapsed or Not Responded to Treatment

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose (MTD) of oral clofarabine when given with LDAC
(cytarabine) in patients age >= 60 with previously treated AML or high risk MDS.

SECONDARY OBJECTIVES:

I. To determine the response rate, disease-free survival (DFS), and overall survival (OS)
after therapy with oral clofarabine and LDAC for previously treated AML or high-risk MDS.

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

Patients receive clofarabine orally (PO) once daily (QD) on days 1-5 and low-dose cytarabine
subcutaneously (SC) twice daily (BID) on days 1-10 or SC QD on days 1-14. Treatment repeats
every 21-28 days for up to 4 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 for 3 years.

Inclusion Criteria:

- Diagnosis of 1st relapse or refractory AML; or patients with high risk MDS (10-19%
blasts) who have received previous therapy 1st remission must have been < 1 year

- Must not have received previous ara-C (cytarabine) or clofarabine

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

- Not candidates for standard 7 + 3 regimen (Ara-C and an anthracycline), high dose
Ara-C, or hematopoietic stem-cell transplantation

- Serum creatinine =< 1.0 mg/dL; if serum creatinine > 1.0 mg/dL, then the estimated
glomerular filtration rate (GFR) must be > 50 L/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 aminotransferase (AST)/alanine aminotransferase (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

- Female patients of childbearing potential must have a negative serum pregnancy test
within 2 weeks prior to enrollment

- Male and female patients should use an effective contraceptive method during the
study and for a minimum of 6 months after study treatment

Exclusion Criteria:

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

- Patients with acute promyelocytic leukemia (APL)

- Use of investigational agents within 30 days or any anticancer therapy within 2 weeks
before study entry with the exception of hydroxyurea; 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

- 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 including
the following:

- Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical
intraepithelial neoplasia, regardless of the disease-free duration, are eligible
for this study 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 are also
eligible for this study if hormonal therapy has been initiated, or a radical
prostatectomy or definitive radiotherapy has been performed

- Have currently active gastrointestinal disease, or prior surgery that may affect the
ability of the patient to absorb oral clofarabine