6,8-Bis(Benzylthio)Octanoic Acid, Cytarabine, and Daunorubicin Hydrochloride in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD). (Phase I) II. To determine treatment
response with the addition of CPI-613 to induction therapy in patients with newly diagnosed
acute myeloid leukemia (AML). (Phase II)

SECONDARY OBJECTIVES:

I. To assess the safety of administering CPI-613 under the proposed study regimen. (Phase
I/II) II. To assess survival endpoints of patients receiving the proposed study regimen.
(Phase II) III. To assess the rate of allogeneic stem cell transplantation. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of 6,8-bis(benzylthio)octanoic acid
followed by a phase II study.

INDUCTION: Patients receive cytarabine intravenously (IV) continuously on days 1-7,
daunorubicin hydrochloride IV on days 1-3, and 6,8-bis(benzylthio)octanoic acid IV over 2
hours on days 3-7. Patients then undergo biopsy on day 14. Patients experiencing significant
residual disease receive cytarabine IV continuously on days 1-5, daunorubicin hydrochloride
IV on days 1-2, and 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-5.

CONSOLIDATION: Beginning 42 days later, patients receive cytarabine IV continuously on days
1-16 and 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 2-6. Treatment repeats
every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients not undergoing transplant after consolidation receive
6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-5. Treatment repeats every 4 weeks
for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 14 days and then every 3
months for 2 years.

Inclusion Criteria:

- Patients must have histologically or cytologically documented newly diagnosed acute
myeloid leukemia (non-acute promyelocytic leukemia [APL]) that has not yet been
treated; hydroxyurea (Hydrea) and tretinoin (ATRA) previous treatments are acceptable

- Hydroxyurea may be used to control leukocytosis and can be taken until day 1 of
therapy; patients with persisting, non-hematologic, non-infectious toxicities from
prior treatment =< grade 2 are eligible, but must be documented as such

- Eastern Cooperative Oncology Group (ECOG) performance status of =< 3 and fit for
induction therapy in the opinion of the treating physician

- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT])
=< 3 X institutional upper limit of normal (=< 5 X upper limit of normal [ULN] if
liver metastases present)

- Bilirubin =< 1.5 X ULN

- Creatinine =< 1.5 mg/dL or 133 umol/L

- International normalized ration (INR) < 1.5

- Albumin >= 2.0 g/dL

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and for
the duration of study participation; should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating physician
immediately

- Ability to understand and the willingness to sign an Institutional Review Board
(IRB)-approved informed consent document

Exclusion Criteria:

- Patients who have received any therapy other than hydroxyurea with the purpose of
treating their AML are not eligible

- Patients having received prior radiotherapy, treatment with cytotoxic agents (except
CPI-613), treatment with biologic agents or any anti-cancer therapy for a non-AML
malignancy within the 2 weeks prior to treatment with CPI-613, or those who have not
fully recovered from the acute, non-hematological, non-infectious toxicities of any
prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities
(returned to baseline status as noted before most recent treatment)

- Patients that have received a chemotherapy regimen with stem cell support in the
previous 6 months

- Patients with known central nervous system involvement should be excluded from this
clinical trial

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to CPI-613

- Uncontrolled concurrent illness including, but not limited to symptomatic congestive
heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with study requirements

- Patients with large and recurrent pleural or peritoneal effusions requiring frequent
drainage (e.g. weekly); patients with any amount of clinically significant pericardial
effusion

- Patients with known human immunodeficiency virus (HIV) infection

- A history of additional risk factors for Torsade de Pointes (e.g., clinically
significant heart failure, hypokalemia, family history of long QT syndrome)

- Pregnant women are excluded from this study; breastfeeding should be discontinued