Clofarabine, Idarubicin, and Cytarabine Combination in Acute Myeloid Leukemia (AML) Induction

The Study Drugs:

Clofarabine is designed to interfere with the growth and development of cancer cells.

Idarubicin is designed to cause breaks in DNA (the genetic material of cells) of cancer cells
and interfere with their growth and development.

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

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive the study drug
combination over 1 or 2 "Induction Cycles" of treatment. Whether or not you receive a second
Induction Cycle depends on the disease's response to the first Induction Cycle. Each
Induction Cycle will last about 4-6 weeks, depending on your reaction to the study drugs.
During each Induction Cycle, you will receive the study drugs by the following schedule:

- Clofarabine, by vein, over 1-2 hours on Days 1-5.

- Cytarabine, by vein, over 2-3 hours on Days 1-5.

- Idarubicin, by vein, over about 30-60 minutes on Days 1-3.

If the disease shows a response to the treatment during the Induction Cycle(s), you may
continue to receive up to 6 "Consolidation Cycles" of treatment. Each Consolidation Cycle
will last about 3-10 weeks, depending on your reaction to the study drugs. During each
Consolidation Cycle, you will receive the study drugs by the following schedule:

- Clofarabine, by vein, over 1-2 hours on Days 1-3.

- Cytarabine, by vein, over 2-3 hours on Days 1-3.

- Idarubicin, by vein, over 30-60 minutes on Days 1-2.

Study Visits:

On Day 1 of every cycle:

- You will have a physical exam, including measurement of your weight and vital signs.

- Your performance status will be recorded.

- Blood (about 1-2 teaspoons) will be drawn for routine tests.

Throughout the study, you will have blood and bone marrow tests to check the status of the
disease and to help the doctor decide if you need additional cycles of treatment. Blood
(about 1-2 tablespoons each time) will be drawn 2 times each week for routine tests during
the Induction Cycles. This blood will also be drawn every week during the Consolidation
Cycles.

About 3 weeks after you first receive the study drugs, you will have a bone marrow aspirate
to check the status of the disease. After that, you will have a bone marrow aspirate every 2
weeks (or more often if your doctor thinks it is needed). However, if the routine blood tests
show that there is still leukemia present, these bone marrow samples may not need to be
collected.

You will need to stay in Houston for up to the first 5 weeks of treatment. After that, you
will need to return to Houston to receive treatment, but you can have check-up visits and
blood tests with your local doctor in between treatments.

Length of Study:

You will be able to receive the study drugs for up to 8 cycles (a maximum of 2 induction
cycles and 6 consolidation cycles). You will be taken off study if the disease gets worse or
you experience any intolerable side effects.

Follow-up Scan:

Within 8 weeks after you have stopped taking the study drug, you will have an echocardiogram
or a Multiple gate acquisition scan (MUGA) scan to check your heart function.

This is an investigational study. Cytarabine and idarubicin are both FDA approved and
commercially available for the treatment of patients with AML. Clofarabine is FDA approved
and commercially available for the treatment of patients with acute lymphoblastic leukemia
(ALL). The use of this drug combination for the treatment of AML is investigational.

Up to 60 patients will take part in this study. All will be enrolled at M. D. Anderson.

Inclusion Criteria:

1. Diagnosis of AML (World Health Organization (WHO) classification)

2. Patients must be chemotherapy-naïve, i.e. not have received any prior cytotoxic
chemotherapy for AML (with the exception of hydroxyurea). They could have received
prior therapy with hypomethylating agents, targeted, or biological agents.

3. Age 18 to 60 years.

4. Eastern Cooperative Oncology Group (ECOG) performance status
5. Serum creatinine 1.0 mg/dL, then the estimated
glomerular filtration rate (GFR) must be > 60 mL/min/1.73m^2 as calculated by the
Modification of Diet in Renal Disease equation where Predicted GFR
(ml/min/1.73m^2)=186 * (serum creatinine)^-1.154 x (age in years)^-0.023 * (0.742 if
patient is female) * (1.212 if patient is black), where SCr is serum creatinine
measured in mg/dL. serum bilirubin increase is due to hemolysis or a congenital disorder); serum transaminases (SGPT
and/or SGOT)
6. Cardiac ejection fraction >/= 45% (by either echocardiography or MUGA scan).

7. Ability to understand and provide signed informed consent.

Exclusion Criteria:

1. Patients with acute promyelocytic leukemia (APL).

2. Any coexisting medical condition that in the judgment of the treating physician is
likely to interfere with study procedures or results.

3. Nursing women, women of childbearing potential with positive urine pregnancy test, or
women of childbearing potential who are not willing to maintain adequate contraception
(such as birth control pills, intrauterine device (IUD), diaphragm, abstinence, or
condoms by their partner) over the entire course of therapy.

4. Active and uncontrolled infection requiring therapy with IV antibiotics or antifungal
therapy. Prior or concurrent history of one or more opportunistic infections (e.g.,
cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria
other than TB).