Clofarabine, Cytarabine, and Filgrastim Followed by Infusion of Non-HLA Matched Ex Vivo Expanded Cord Blood Progenitors in Treating Patients With Acute Myeloid Leukemia

PRIMARY OBJECTIVES:

I. Assess the safety of infusing off-the-shelf non-HLA matched expanded cord blood cells
following administration of cytarabine hydrochloride (GCLAC) for patients with AML.

SECONDARY OBJECTIVES:

I. Assess the ability of the product to provide temporary myeloid engraftment.

II. Assess the kinetics/persistence of potential engraftment.

III. Assess the kinetics of autologous recovery when compared to historical cohorts.

IV. Assess the development of alloimmunization.

OUTLINE:

INDUCTION THERAPY: Patients receive clofarabine intravenously (IV) over 1 hour and cytarabine
hydrochloride IV over 2 hours on days 1-5. Patients receive an infusion of non-HLA matched ex
vivo expanded cord blood progenitors on day 6. Filgrastim (G-CSF) is administered
subcutaneously (SC) on days 0-5 and from day 7 until blood counts recover. Treatment
modifications may apply according to response.

CONSOLIDATION THERAPY: Patients receive clofarabine IV over 1 hour and cytarabine
hydrochloride IV over 2 hours on days 1-5. Patients also receive G-CSF SC beginning on day 0
and continuing until blood counts recover.

Patients may receive treatment for 1-4 courses in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed up every 3-6 months for 2 years
and then annually for 3 years.

Inclusion Criteria:

- Cohort A: Diagnosis of AML by World Health Organization (WHO) criteria, either
relapsed or refractory; acute promyelocytic leukemia [Acute promyelocytic leukemia
with t(15;17)(q22;q12) and variants] will be eligible only after failure of a regimen
containing arsenic trioxide; patients in this cohort must have had an initial
remission duration of < 1 year and cannot have received any prior salvage chemotherapy

- Cohort B: Untreated AML patients, excluding those with favorable cytogenetic or
molecular abnormalities per the European LeukemiaNet recommendations

- Cohort C: Untreated AML patients, including those with favorable cytogenetic or
molecular abnormalities per the European LeukemiaNet recommendations

- The first three patients enrolled in cohorts A and B must be less than 60 years old;
thereafter, patients aged >= 18 and =< 70 are eligible

- The first three patients enrolled in cohorts A and B must have an Eastern Cooperative
Oncology Group (ECOG) performance status of 0 -1; thereafter, ECOG performance status
of 0-2 is required

- Serum creatinine =< 1.0 mg/dL; if serum creatinine > 1.0 mg/dl, then the estimated
glomerular filtration rate (GFR) must be > 60 mL/min/1.73 m^2 as calculated by the
Modification of Diet in Renal Disease equation where predicted GFR (ml/min/1.73 m^2) =
186 X (Serum Creatinine)^-1.154 X (age in years)^-0.203 X (0.742 if patient is female)
X (1.212 if patient is black)

- Serum total bilirubin =< 1.5 x upper limit of normal (ULN) unless elevation is thought
to be due to Gilbert's syndrome, hemolysis, or hepatic infiltration by the hematologic
malignancy

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 X ULN, unless
elevation is thought to be due to hepatic infiltration by the hematologic malignancy

- 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 must be willing to use an effective contraceptive method
during the study and for a minimum of 90 days after study treatment

Exclusion Criteria:

- Allogeneic transplant recipients

- Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as
specified in the protocol with the exception of intrathecal chemotherapy administered
on days that are not concurrent with clofarabine and cytarabine

- Have any other severe concurrent disease, or have a history of serious organ
dysfunction or disease involving the heart, kidney, liver (including symptomatic
hepatitis, veno-occlusive disease), or other organ system dysfunction

- 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