A Pilot Study of ODSH in Acute Myeloid Leukemia

This is an open-label, multi-center, 10 patient pilot study with an anticipated 1 year
enrollment period

Primary Objectives:

1. To evaluate the safety and tolerability of ODSH in patients with Acute Myeloid Leukemia
(AML) receiving cytarabine and idarubicin induction or cytarabine consolidation
chemotherapy.

2. To determine whether there is preliminary evidence of an effect of ODSH on time to
transfusion-independent platelet recovery in Acute Myeloid Leukemia (AML) patients
receiving cytarabine and idarubicin induction or cytarabine consolidation chemotherapy.

Secondary Objectives:

1. To determine whether there is preliminary evidence of an effect of ODSH on remission
rate following cytarabine and idarubicin induction in Acute Myeloid Leukemia (AML)
patients.

2. To determine whether there is preliminary evidence of an effect of ODSH on improving
platelet nadir counts in Acute Myeloid Leukemia (AML) patients receiving cytarabine and
idarubicin induction or cytarabine consolidation chemotherapy.

3. To determine whether there is preliminary evidence of an effect of ODSH on decreasing
the number of platelet transfusions in Acute Myeloid Leukemia (AML) patients receiving
cytarabine and idarubicin induction or cytarabine consolidation chemotherapy.

4. To determine whether there is preliminary evidence of an effect of ODSH on reducing
overall side effects of chemotherapy in Acute Myeloid Leukemia (AML) patients receiving
cytarabine and idarubicin induction or cytarabine consolidation chemotherapy.

Enrollment for newly diagnosed, previously untreated acute myeloid leukemia. Acute
promyelocytic leukemia and acute megakaryoblastic leukemia subtypes are excluded.

All patients will receive standard induction chemotherapy with cytarabine 100 mg/m2/day by
continuous intravenous infusion over 24 hours daily for 7 days (D 1-7) plus idarubicin 12
mg/m2/day by intravenous injection daily for 3 days (D 1-3). For consolidation, patients
younger than 60 will receive cytarabine at a dose of 3 grams/m2 over 3 hours, every 12 hours
on days 1, 3, and 5.

Induction cycle: ODSH 4 mg/kg IV bolus day 1, 30 minutes after completion of administration
of the first dose of idarubicin, then ODSH 0.25 mg/kg/hour for 24 hours daily by continuous
IV infusion days 1-7.

Consolidation cycle: ODSH 4 mg/kg IV bolus day 1 administered 30 minutes after completion of
infusion of the first dose of cytarabine then ODSH 0.25 mg/kg/hour for 24 hours daily by
continuous IV infusion days 1-5

7 days in induction cycle and 5 days in consolidation cycles

Inclusion Criteria:

- Newly diagnosed, previously untreated acute myeloid leukemia. Acute promyelocytic
leukemia and acute megakaryoblastic leukemia subtypes are excluded

- No prior chemotherapy for acute myeloid leukemia; however, prior hydroxyurea to
control white blood cell count is allowed

- Age: ≥18

- Eastern Cooperative Oncology Group (ECOG) Performance status 0-2

- Cardiac ejection fraction ≥ 50% (echocardiography or Multi-Gated Acquisition Scan
[MUGA])

- Adequate hepatic and renal function (aspartate aminotransferase [AST], alanine
aminotransferase [ALT], bilirubin and creatinine < 2.5 x upper normal limit).

- Able to provide informed consent and have signed an approved consent form that
conforms to federal and institutional guidelines.

Exclusion Criteria:

- Patients with acute promyelocytic leukemia

- Patients with acute megakaryoblastic leukemia

- Patients with Central Nervous System (CNS) leukemia

- Presence of uncontrolled bleeding

- Presence of significant active infection that is uncontrolled as judged by the
investigator

- History of severe congestive heart failure or other cardiac disease that
contraindicates the use of anthracyclines, including idarubicin

- Pre-existing liver disease

- Renal insufficiency, which, in the opinion of the investigator, might adversely affect
schedule and dose of therapy with cytarabine as well as management of tumor lysis
syndrome. Patients with creatinine levels ≥2 mg/dl are not eligible

- Use of recreational drugs or history of drug addiction, within the prior 6 months

- Known history of positive hepatitis B surface antigens or hepatitis C virus (HCV)
antibodies

- Known history of positive test for Human Immunodeficiency Virus (HIV) antibodies

- Psychiatric or neurologic conditions that could compromise patient safety or
compliance, or interfere with the ability to give proper informed consent

- History of other active malignant disease within 5 years, other than cured basal cell
carcinoma of the skin, cured in situ carcinoma of the cervix, or localized prostate
cancer that has received definitive therapy. Such prostate cancer patients who are
receiving hormonal therapy are eligible

- Presence of disseminated intravascular coagulation, as confirmed by laboratory studies
demonstrating evidence of both increased thrombin generation (decreased fibrinogen,
prolonged Prothrombin Time [PT] and Partial Thromboplastin Time [aPTT]) as well as
increased fibrinolysis (elevated D-dimer level)

- Patients receiving any form of anticoagulant therapy

- Presence of a known bleeding disorder or coagulation abnormality

- Treatment with any other investigational agent within 7 days prior to study entry. All
prior toxicities should have resolved to no greater than Grade 1 (with the exception
of alopecia)

- Pregnant or breast-feeding patients

- Patient with childbearing potential not using adequate contraception

- Any condition that requires maintenance of platelet counts at 50,000/μL or higher.