Clinical Trial of Oral Ciprofloxacin and Etoposide in Subjects With Resistant Acute Myeloid Leukemia (AML)(UF-AML-CE-101)

This study will look at: any side effects that occur, the effectiveness of the study drug,
and how your disease reacts to ciprofloxacin in combination with etoposide. This study will
try to find the highest tolerated dose of ciprofloxacin without causing serious side effects.
This study will also look to see how your AML responds to the drugs using laboratory tests.

Ciprofloxacin is a commonly used antibiotic drug that is approved for use by the United
States Food and Drug Administration (FDA). The FDA has not approved ciprofloxacin to treat
AML. Etoposide is an anticancer chemotherapy drug that is approved for use by the FDA for the
treatment of small cell lung cancer and testicular cancer. Etoposide is also used for
treatment of various blood cancers.

There is laboratory research that has shown that ciprofloxacin can make leukemia cells more
sensitive to etoposide chemotherapy. This observation indicates that ciprofloxacin may help
improve the effectiveness of etoposide in the treatment of resistant AML.

Inclusion Criteria:

- Diagnosis of AML confirmed by review of bone marrow pathology at the University of
Florida.

- Failure to achieve complete remission (CR) or complete remission with incomplete blood
count recovery (CRi) after at least 2 cycles of induction chemotherapy, or has
relapsed after any duration of response.

- Per the treating physician, the subject must have a life expectancy of >= 4 weeks.

- Subject performance status must be Eastern Cooperative Oncology Group (ECOG) 0, 1, or
2.

- Subject must have a total bilirubin <= 2 mg/dL and aspartate aminotransferase (AST)
and alanine aminotransferase (ALT) <= 2.5 times the upper limit of normal.

- Subject must have serum creatinine < 2 mg/dL.

- Females of child-bearing potential may participate, provided they meet the following
conditions: Must agree to use physician-approved contraceptive methods throughout the
study and for 6 months following the last dose of ciprofloxacin and/or etoposide; Must
have a negative serum pregnancy test within 7 days prior to beginning treatment on
this study.

- Males with female partners of child-bearing potential must agree to use
physician-approved contraceptive methods throughout the study and should avoid
conceiving children for 6 months following the last dose of ciprofloxacin and/or
etoposide.

- Must provide written informed consent and be willing to comply with all study-related
procedures.

Exclusion Criteria:

- History of allergic or significant adverse reaction [e.g., anaphylaxis, prolonged QTc
(corrected QT interval), or severe tendonitis] to ciprofloxacin or etoposide.

- Acute promyelocytic leukemia (APL) with t(15;17).

- Prolonged baseline QTc, defined as QTc interval > 470 msec in women and > 450 msec in
men, or > 480 msec in subjects with a bundle branch block.

- Uncontrolled, clinically significant infection. Subjects with a fever (temperature >=
38.3) thought to be related to leukemia are eligible assuming that blood cultures are
negative during the 7 days prior to Cycle 1 Day 1 and there is no clinical evidence of
active infection (e.g., negative or stable radiographs and negative physical
examination).

- Ongoing, symptomatic Clostridium difficile infection. Subjects who are asymptomatic
with negative stool for C. difficile may participate.

- Pregnant and or nursing.

- History of Myasthenia Gravis.

- Treatment with any anticancer therapy (standard or investigational) within 14 days
prior to the first dose of ciprofloxacin or less than full recovery from the
clinically significant toxic effects of that treatment. The use of hydroxyurea is
allowed only during the first 14 days of Cycle 1.