E7070, Idarubicin and Cytarabine in Relapsed AML and High-Risk Myelodysplastic Syndromes

The Study Drugs:

E7070 is designed to stop metabolic ingredients from reaching the cancer cells and to stop
the cancer cell from dividing.

Cytarabine is designed to insert itself into DNA (the genetic material of cells) of cancer
cells and stop the DNA from repairing itself.

Idarubicin is designed to cause breaks in both strands of DNA (the genetic material of
cells).

Dexamethasone is a corticosteroid that is similar to a natural hormone made by your body.
Dexamethasone is often given to AML patients in combination with other chemotherapy to treat
cancer.

Study Drug Administration:

If you are found eligible to take part in this study, you will receive E7070 by vein over 1
hour on Day 1 and Day 8 (+/- 2 days on Day 8 only) followed by idarubicin by vein over 1 hour
on Days 9-11. You will also receive cytarabine by vein over 24 hours each day on Days 9-12.
If you are 60 years of age or older, you will only receive cytarabine on Days 9-11. On days
that you are receiving the cytarabine infusions, you will also receive dexamethasone by vein
over about 30 minutes. You will receive dexamethasone before the cytarabine infusions. Each
study cycle is about 28 days.

If your doctor thinks you are benefitting from taking the E7070 in combination with
idarubicin, cytarabine, and dexamethasone, you may receive up to 2 additional cycles of the
study drug combination.

Study Visits:

During Cycle 1, the following tests and procedures will be performed:

- You will be asked about medications you are taking and side effects you may have had.

- Blood (about 2 teaspoons) will be drawn at least 1 time every week for routine tests and
to check your liver and kidney function.

- You will have a bone marrow aspirate on Day 28 (+/- 3 days) to check the status of the
disease. You may have additional bone marrow aspirates during Cycle 2 if the doctor
thinks it is necessary.

- During Cycle 1 only, you will have an ECG on Day 2 (+/- 1 day) and Day 8 (+/- 2 days).

Treatment cycles beyond Cycle 1, the following tests and procedures will be performed:

- You will be asked about medications you are taking and side effects you may have had.

- Blood (about 2 teaspoons) will be drawn every 2-4 weeks for routine tests.

- You will have a bone marrow aspirate to check the status of the disease whenever the
doctor feels it is necessary.

Length of Study:

If the doctor thinks you are benefitting with E7070 in combination with idarubicin,
cytarabine and dexamethasone, you may receive 2 additional cycles of therapy (a total of 3
cycles on this study.)

You will be taken off study if the disease gets worse, you experience intolerable side
effects, or if the study doctor thinks it is in your best interest.

End-of-Treatment Visit:

At the end of treatment, blood (about 2 teaspoons) will be drawn for routine tests within 30
days (+/- 5 days) of your last dose of the study drug combination. You will also be asked
about any side effects you may have had.

Long Term Follow-up (unless you have started on alternative therapy):

Blood (about 1 tablespoon) will be drawn for routine tests every 2-3 months for up to 2 years
unless the disease gets worse or you start on another treatment.

This is an investigational study. E7070 is not FDA-approved or commercially available for use
in patients with AML or MDS that has relapsed. Its use in this study is considered
investigational. Idarubicin, cytarabine, and dexamethasone are FDA-approved and commercially
available for use in the treatment of AML. The combination of E7070, idarubicin, cytarabine,
and dexamethasone in this study is investigational.

Up to 40 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. All patients with histologically or cytologically confirmed relapsed or refractory
acute myeloid leukemia (AML) [except acute promyelocytic leukemia], or high-risk
myelodysplastic syndrome (HRMDS) (Int-2 high risk by International Prostate Symptom
Score (IPSS) or >10% blasts in marrow).

2. Patients must be 18 years or older.

3. Patients must have a performance status of 0-2 (Zubrod scale).

4. Patients must have adequate renal function (serum creatinine less than or equal to 1.3
mg/dL and/or creatinine clearance > 40 mL/min). Patients with renal dysfunction due to
organ infiltration by disease may be eligible after discussion with the Principal
Investigator (PI) (up to creatinine less than or equal to 2.0), and appropriate dose
adjustments will be considered.

5. Patients must have adequate hepatic function (bilirubin less than or equal to 2.0
mg/dl; SGOT or Serum glutamic pyruvic transaminase (SGPT) less than or equal to 3
times the ULN for the reference lab unless due to leukemia or congenital hemolytic
disorder or bilirubin). Patients with hepatic dysfunction (SGOT/SGPT up to less than
or equal to 5 X ULN) due to organ infiltration by disease may be eligible after
discussion with the PI, and appropriate dose adjustments will be considered.

6. Patients must have normal cardiac ejection fraction

7. QTc interval
8. Patients must sign an informed consent form indicating that they are aware of the
investigational nature of this study, in keeping with the policies of the hospital.

9. Female patients must not be pregnant or lactating. Female patients of childbearing
potential (including those <1 year post-menopausal) and male patients must agree to
use contraception.

Exclusion Criteria:

1. Patients must not have untreated or uncontrolled life-threatening infection.

2. Patients must not have received chemotherapy and/or radiation therapy within 2 weeks.
Hydroxyurea is allowed up to 48 hours prior to starting therapy in the setting of
rapidly proliferating disease. Use of hydroxyurea to control proliferative disease
will be allowed starting from day 2 until day 7 Cycle 1. Maximum dose of hydroxyurea
allowed daily is 5 gram and hydroxyurea must be discontinued once administration of
idarubicin and cytarabine is started.

3. Any other medical condition, including mental illness or substance abuse, deemed by
the PI to be likely to interfere with a patient's ability to sign informed consent or
cooperate and participate in the study or with the interpretation of the results.

4. Patients must not have received an investigational anti-cancer drug within two weeks
of E7070 administration.