LY2606368 in Combination With Cytarabine and Fludarabine in Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome (HRMDS)

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose
level of LY2606368 based on when you join the study. Up to 5 dose levels of LY2606368 will be
tested. The first group enrolled will receive a low dose level. If no intolerable or serious
side effects are seen in this group, the next group will receive a higher dose level. This
will continue until the highest tolerable dose level of LY2606368 is found.

Once the highest tolerable dose of LY2606368 is found, up to 20 participants will be enrolled
to receive the drug at a dose that was found to be well tolerated in the earlier part of the
study in order to further study the safety and effectiveness of the drug.

All participants will also receive the same dose level fludarabine and cytarabine.

Study Drug Administration:

Treatment on this study is given in 2 phases: Induction and Consolidation. Each cycle is 28
days.

Induction Phase:

You will receive 1 cycle of treatment during the Induction phase. You may be admitted to the
inpatient leukemia service when you receive the study drugs.

On Days 1-4, you will receive cytarabine by vein non-stop and fludarabine by vein over about
2 hours. If you are over the age of 65, cytarabine and fludarabine will be given only on Days
1-3.

You will receive LY2606368 by vein over 2 hours for up to 5 days, depending on which dose
level of LY2606368 you are assigned.

If the disease does not respond during Cycle 1, you may be allowed to receive an additional
Induction cycle, which will also be called Cycle 1. If you respond well to the study drug
during Induction, you can move to Consolidation therapy.

Consolidation Therapy:

You may continue with Consolidation therapy for 3 additional cycles.

During Days 1-3 of each cycle, you will receive cytarabine by vein non-stop and fludarabine
by vein over 2 hours. On Days 1-2, you will receive LY2606368 by vein over 2 hours.

Study Visits:

Induction Phase:

On Day 1 (or up to 7 days before) of Cycle 1, you will have a physical exam.

On Days 1, 3, and 5 of Cycle 1, blood (about 2 teaspoons) will be drawn for PD testing.

On Days 1 and 4 or 5 of Cycle 1, you will have an EKG.

Every week, blood (about 2 teaspoons) will be drawn for routine tests

On Day 28 (± 3 days) of Cycle 1, you will have a bone marrow aspirate and/or biopsy to check
the status of the disease.

Any time the doctor thinks it is needed, you will have additional blood tests.

Consolidation Therapy:

On Day 1 of each cycle, you will have a physical exam.

Every week, blood (about 2 teaspoons) will be drawn for routine tests

Any time the doctor thinks it is needed, you will have a bone marrow aspiration/biopsy.

Length of Treatment:

You may continue taking the study drug for up to 5 cycles (2 cycles during Induction, 3
cycles during Consolidation). You will no longer be able to take the study drug if the
disease gets worse, if intolerable side effects occur, or if you are unable to follow study
directions.

Your participation on the study will be over after the follow-up visits.

End-of-Treatment Visit:

About 30 days (+/- 5 days) after your last dose of study drugs:

- You will have a physical exam.

- Blood (about 2 teaspoons) and urine will be collected for routine tests.

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

- You will have a bone marrow aspirate and/or biopsy to check the status of the disease.

Follow-Up Visits:

If the disease appears to get better after the end-of-treatment visit, every 2-3 months for
up to 2 years:

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

- You will have a physical exam.

These tests can be performed by your local doctor.

This is an investigational study. LY2606368 is not FDA approved or commercially available. It
is being used for research purposes only. Cytarabine and fludarabine are FDA approved and
commercially available to treat certain types of leukemia. Their use in this study in
combination with LY2606368 is considered investigational.

Up to 40 participants 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 relapsed or
refractory high-risk myelodysplastic syndrome (HRMDS) (Int-2 or higher risk by IPSS);
patients with chronic myelomonocytic leukemia (CMML) can be enrolled if they can be
classified as HRMDS using MDS criteria. Patients should not have received more than
one salvage therapy. Second induction regimen or stem cell transplant in remission
will be considered salvage therapy. Refractory subjects, up to second consecutive
salvage.

2. Patients must be 18 years or older.

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

5. Patients must have adequate hepatic function (bilirubin less than or equal to 1.5
mg/dl (unless due to Gilbert's syndrome); SGOT/AST or SGPT/ALT less than or equal to
2.5 X the upper limit of normal (ULN) for the reference lab.

6. Patients must have normal cardiac ejection fraction (LVEF >/= 45%).

7. QTc interval arrhythmias.

8. 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.

9. Patients who have received prior stem cell transplantation will be allowed to enroll
as long as prior transplantation has been at least 3 months before enrollment in the
trial and any transplant related toxicities have subsided to Grade 1 or less.

Exclusion Criteria:

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

2. Patients must not have been treated with CHK1/2 inhibitors.

3. Patients must not have received chemotherapy and/or radiation therapy within 2 weeks
of start of protocol treatment. Hydroxyurea is allowed up to 48 hours prior to
starting therapy in the setting of rapidly proliferating disease.

4. Patients must not have received an investigational anti-cancer drug within two weeks
of start of protocol treatment.

5. Patients must not have active central nervous system leukemia. Patients with history
of CNS leukemia with no evidence of active CNS disease may be enrolled. Maintenance
intrathecal chemotherapy for adequately treated CNS involvement with leukemia is
allowed with approval from the study supporter.

6. Patients must not have significant cardiac co-morbidity including: History of acute
coronary syndromes (including myocardial infarction and unstable angina) within 12
months; coronary angioplasty or stenting within 6 months; history or evidence of
current >/= Class III congestive heart failure as defined by the New York Heart
Association (NYHA); patients with intra-cardiac defibrillators or permanent
pacemakers.