Study of CPX-351 (Cytarabine:Daunorubicin) Liposome Injection in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) at High Risk for Induction Mortality

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as
in the flip of a coin) to 1 of 2 study groups. This is done because no one knows if one study
group is better, the same, or worse than the other group:

- If you are in Group 1, you will receive a lower dose of CPX-351.

- If you are in Group 2, you will receive a higher dose of CPX-351.

Up to 15 participants will be assigned to each study group. You and the study staff will know
which group you are in. If both groups are found to be safe, a third group of up to 15
participants will receive an even higher dose of the study drug. The group that appears to
have the best results will also enroll an additional 10 participants.

Study Drug Administration:

Each study cycle is about 4-8 weeks long, but may be longer depending on how the disease
responds to the study drug. The study cycles will be Induction and Consolidation Cycles.
Induction Therapy is designed to remove the signs of leukemia that can be seen and to allow
normal blood cells to be restored. This is called remission. Consolidation Therapy is
designed to cause the disease to stay in remission.

You will receive CPX-351 by vein over about 90 minutes on Days 1, 3, and 5 of an Induction
Cycle. If the disease does not appear to go into remission, you may receive a second
Induction Cycle, in which you receive the drug on Days 1 and 3. No more than 2 Induction
Cycles will be given.

If the disease appears to go into remission, you may receive up to 4 Consolidation Cycles, in
which you receive the drug on Days 1 and 3.

Study Visits:

Because the length of study cycles will depend on how the disease responds to the study drug,
some of the visits listed below may not be needed. For example, if a study cycle is only 4
weeks, you will not have a Day 42 visit in that cycle.

On Days 14 and 42 of each course, you will have a physical exam.

On Days 1, 3, 5, 7, 10, 14, then at least 1 time every week after that, blood (about 2
teaspoons) will be drawn for routine tests.

Before the next cycle, blood (about 1 teaspoons) will be drawn to check your copper levels.

On Day 28 of each Induction cycle, you will have a bone marrow aspiration and/or biopsy to
check the status of the disease and for cytogenetic testing. If the doctor thinks it is
needed, you will have another bone marrow aspiration/biopsy 5-10 days after this one.

Before every 2 cycles of treatment, you will have an ECHO or MUGA scan to check your heart
function. If the study doctor thinks it is needed, this will be done before every cycle.

Length of Treatment:

You may receive the study drug for up to 2 induction and 4 consolidation cycles. You will no
longer be able to receive the study drug if the disease gets worse, if intolerable side
effects occur, or if you are not able to follow the study directions.

End of Treatment Visit:

Within 30 days after the last dose of the study drug:

- You will have a physical exam.

- Blood (about 2 teaspoons) will be drawn for routine tests and to check your copper
levels.

- You will have an EKG, ECHO, and/or MUGA scan to check your heart function.

Follow-Up:

After the end-of-treatment visit, the following tests and procedures will be performed:

- Every month for as long as the study doctor thinks it is needed, you will be called and
asked about how you are doing. Each call should last about 5-10 minutes.

- Every 2-3 months for up to 1 year, then as often as the study doctor thinks it is
needed, blood (about 2 teaspoons) will be drawn for routine tests and to check your
copper levels. If the study doctor thinks it is needed, blood will be drawn for copper
level testing every month.

- Every 3-4 months for up to 1 year, then for as often as the study doctor thinks it is
needed, you will have a bone marrow aspiration and/or biopsy to check the status of the
disease.

- If the study doctor thinks it is needed, every 3-4 months for up to 1 year, you will
have an ECHO or MUGA scan to check your heart function.

This is an investigational study. CPX-351 is not FDA approved or commercially available. It
is currently being used for research purposes only.

The study doctor can explain how the study drug is designed to work.

Up to 55 participants will be enrolled in this study. All will take part at MD Anderson.

Inclusion Criteria:

1. Ability to understand and voluntarily sign an informed consent form.

2. Age >18 years at the time of diagnosis of AML.

3. Pathological diagnosis of AML according to WHO criteria (with at least 20% blasts in
the peripheral blood or bone marrow): Newly Diagnosed De novo AML; except for APL;
Newly Diagnosed Secondary AML, defined as having a history of an antecedent
hematologic disorder (myelodysplastic syndromes [MDS], myeloproliferative disease
[MPD] or history of cytotoxic treatment for non-hematologic malignancy) or apparent de
novo AML with MDS-associated karyotype.

4. Eastern Cooperative Oncology Group (ECOG) performance status 0-3.

5. Laboratory values fulfilling the following: Serum creatinine total bilirubin If elevated liver enzymes are related to disease ALT should be < 5 times ULN.

6. To be considered at high risk for induction mortality patients must have 1 or 2 of the
following risk factors (patients >/=60 must have at least 1 risk factor, patients <60
must have at least 2 risk factors) present. At least one risk factor in every patient
must be an AML-related factor: AML-related factors include: AHD (MDS, CMML, or MPD) or
history of exposure to cytotoxic chemotherapy (t-AML)), or WHO-defined AML with
MDS-related changes or apparent de novo AML with MDS-associated karyotype; Unfavorable
cytogenetics as defined by the European Leukemia Net. Patient-related factors: Age
>/=70; ECOG PS >/=2; Co-morbidities: Serum creatinine >1.3 g/dL .

7. Cardiac ejection fraction >/= 50% by echocardiography or MUGA (when LVEF expressed as
a range, at least the upper limit should include 50%).

8. Able to adhere to the study visit schedule and other protocol requirements.

9. All men and women must agree to practice effective contraception during the study
period if not otherwise documented to be infertile.

Exclusion Criteria:

1. Patients with history of second malignancy are eligible if they have documentation of
disease stability, off therapy, based on CT scan or other measures for the 6 months
prior to entry in core.

2. Any serious medical condition or psychiatric illness that would prevent the patient
from providing informed consent.

3. Chemotherapy or other investigational anticancer therapeutic drugs in the two weeks
prior to study entry; in the event of rapidly proliferative disease, however, the use
of hydroxyurea is permitted up to 24 hours before study entry in core.

4. Evidence of active CNS leukemia.

5. Pregnant or lactating women.

6. Uncontrolled infection; to be eligible, patients receiving treatment for an infection
(antibiotic, antifungal or antiviral treatment) must be afebrile (<38.3 degrees C) and
without hemodynamic instability or dyspnea from pneumonia for >48 hrs prior to the
start of induction therapy.

7. Hypersensitivity to cytarabine, daunorubicin or liposomal products.

8. History of Wilson's disease or other copper-metabolism disorder.