Ficlatuzumab With High Dose Cytarabine in Relapsed and Refractory AML

Inclusion Criteria:

- Relapsed or refractory AML as defined by one of the following criteria:

1. First relapse within 12 months after date of first CR or CRi

2. Persistent AML documented by bone marrow biopsy at least 28 days after day 1 of
the first induction cycle of cytotoxic chemotherapy

3. Hypercellular bone marrow with greater than 20% cellularity and 10% blasts at
least 14 days after first induction cycle day 1

- Age >=18

- Prior induction therapy had to include no more than two cycles of cytotoxic
chemotherapy and at least one induction cycle must have consisted of an anthracycline
or anthracenedione and cytarabine combination with a reasonable schedule/dose
according to the discretion of the investigator

- Histologically confirmed AML by hematopathology review performed within four weeks
prior to study entry

- Ejection fraction >=40% by transthoracic echocardiogram or radionuclide
ventriculogram, i.e. MUGA scan

- Treatment for non-hematologic malignancy greater than 6 months prior to enrollment is
acceptable.

- Transplantation for AML (allogeneic or autologous) allowed unless within 90 days of
study entry

- No active graft versus host disease (GVHD) or immunosuppression for prevention or
treatment of GVHD within two weeks of study entry

- Prior treatment of myelodysplastic syndrome or myeloproliferative neoplasm with
hypomethylating agent acceptable.

- Cytoreduction therapy with plasmapheresis or hydroxyurea acceptable.

- Females must have a negative serum pregnancy test 24 hours prior to the start of
treatment or be surgically or biologically sterile or postmenopausal (amenorrheic for
at least 12 months)

- Adequate liver function as defined by total bilirubin ≤ 2.0 mg/dL (≤ 3.0 mg/dL for
patients with known Gilbert's syndrome) and AST/ALT ≤ 3 times upper limit of normal,
unless these are thought to be due to AML

- Adequate renal function with creatinine ≤ 2.0 mg/dL

- The effects of ficlatuzumab on the developing human fetus are unknown. For this reason
and because cytarabine is pregnancy category D, women of child-bearing potential and
men must agree to use adequate contraception: hormone, barrier method of birth
control, or abstinence prior to study entry and for the duration of study
participation. Should a woman become pregnant or suspect she is pregnant while she or
her partner is participating in this study, she should inform her treating physician
immediately. Men treated or enrolled on this protocol must also agree to use adequate
contraception prior to the study, for the duration of study participation, and at
least one month after completion of study drug administration.

- Ability to understand a written informed consent document, and the willingness to sign
it

Exclusion Criteria:

- Acute promyelocytic leukemia (FAB M3 AML)

- More than 2 cycles of prior induction therapy for AML

- Allogeneic or autologous transplant for AML with infusion of stem cells within 90 days
of study entry or on active immunosuppressive therapy for (GVHD) within 2 weeks before
study entry

- Cytarabine containing regimen in excess of 2 g/m2/day within 6 months of study entry

- Chemotherapy, radiation, or immunotherapy, within 2 weeks prior to study entry, other
than those specified in the inclusion criteria (hydroxyurea and hypomethylating
agents)

- Known active HIV, hepatitis B or C or infection. Exception for patients with hepatitis
B on antivirals and low viral load, to be determined at the discretion of the
investigator.

- Uncontrolled infection

- Uncontrolled intercurrent illness or psychiatric illness/social situations that would
limit compliance with study requirements

- Active second malignancy that in the opinion of the PI may interfere with or be
adversely affected by this treatment.

- Prior exposure to the investigational agent or anti-c-Met, anti-HGF or anti-VEGF
directed therapy within six months prior to study entry

- Prior grade 4 toxicity attributed to cytarabine

- Known or suspected drug sensitivity to cytarabine or the investigational agent
ficlatuzumab

- Inability to provide consent

- Pregnant women are excluded from this study because the effect of ficlatuzumab on the
developing fetus remains unknown and that cytarabine is a pregnancy risk category D
drug with known teratogenic or abortifacient effects. Because of the potential adverse
events in nursing infants secondary to treatment of the mother with ficlatuzumab and
cytarabine, breastfeeding should be discontinued while on study. Patients who become
pregnant while on study will be removed from the study once the pregnancy is
confirmed.