LY2510924, Idarubicin and Cytarabine in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study
group based on when you join this study. Up to 3 groups of up to 6 participants each will be
enrolled in the Dose Escalation part of the study, and up to 18 participants will be enrolled
in Dose Expansion part of the study.

If you are enrolled in the Dose Escalation part of the study, the dose of LY2510924 you
receive will depend on when you join this study. The first group of participants will receive
the lowest dose level of LY2510924. Each new group will receive a higher dose of LY2510924
than the group before it, if no intolerable side effects were seen. This will continue until
the highest tolerable dose of LY2510924 is found.

If you are enrolled in the Dose Expansion part of the study, you will receive LY2510924 at
the highest dose that was tolerated in the Dose Expansion part of the study.

All participants will also receive idarubicin and cytarabine. Your dose level will be
assigned based on your age.

Study Drug Administration:

Treatment on this study is given in 2 phases: Induction and Consolidation. Each phase is made
up of 28-day study cycles.

Induction Phase:

You will receive 1-2 cycles during the Induction phase. During Cycle 1, you will be admitted
to the inpatient Leukemia service when you receive the study drugs.

You will receive LY2510924 alone each day for 7 days and then together with chemotherapy on
Days 8, 9 and 10 and also on Day 11 if you are under the age of 60, of every 28-day cycle.

- On days that you do not receive idarubicin/cytarabine, LY2510924 will be given as an
injection under the skin at about 8:00 am (+/- 1½ hours).

- On days when you do receive idarubicin/cytarabine, it will be given about 4 hours (+/- ½
hour) before you receive idarubicin.

On Days 8 and 9, in addition to LY2510924:

- You will receive idarubicin by vein over about 1 hour.

- You will receive cytarabine by vein over about 24 hours.

On Day 10, in addition to LY2510924:

- You will receive cytarabine by vein over about 24 hours.

- If you are under age 60, you will receive idarubicin by vein over about 1 hour.

If you are under age 60, on Day 11, in addition to LY2510924, you will receive cytarabine by
vein over about 24 hours.

On days that you are receiving the cytarabine infusions, you will receive drugs to help
reduce the risk of side effects. You will receive dexamethasone before the cytarabine
infusion by vein over about 30 minutes. You will also receive corticosteroid-containing eye
drops during this time and for 2 days following the last dose of cytarabine.

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 do respond to Induction, you can
move to the Consolidation phase.

Consolidation Phase:

If you are benefitting from the treatment, you may continue with Consolidation therapy for an
additional 4-6 cycles.

During these cycles, you will receive LY2510924 in the same way as during earlier cycles, for
3 days with chemotherapy. During Consolidation, all participants will receive idarubicin by
vein over 1 hour on Days 1 and 2, and cytarabine by vein over 24 hours on Days 1-3.

Study Visits:

During Days 1-12 of Cycle 1 (if over the age of 60, Days 1-10), blood (about 4 teaspoons)
will be drawn for routine tests. During Days 1-7, blood (about 2 teaspoons) will be drawn 4
hours after your injection with LY2510924 for routine tests.

On Days 8 and 28 of Cycle 1, you will have a bone marrow biopsy/aspirate to check the status
of the disease.

After Day 11 of Cycle 1, blood (about 4 teaspoons) will be drawn every 2-4 days for routine
tests.

Every 1-2 weeks during Cycles 2-6, blood (about 4 teaspoons) will be drawn for routine tests.

Every 2-4 weeks during Cycles 2-6, you will have a physical exam.

After Cycles 4 and 6, you will have a bone marrow biopsy and aspiration to check the status
of the disease. You will also have an EKG and either an ECHO or MUGA scan.

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

Length of Study:

You may receive up to 8 cycles of the study drugs. 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.

Your participation on this study will be over after you complete the End-of-Treatment Visit.

End-of-Treatment Visit:

About 30 days (+/- 5 days) after your last dose of the study drugs, blood (about 2 teaspoons)
will be drawn for routine tests.

Long Term Follow-up:

Every 2-3 months for up to 2 years after you stop receiving the study drugs, blood (about 4
teaspoons) will be drawn for routine tests. This can be performed at your local doctor's
office. You should also have a bone marrow aspiration/biopsy every 3 months for the first
year, and then more after that if the doctor thinks it is in your best interest. If any of
these tests show abnormal results, you will return to the study clinic for follow-up testing.

Inclusion Criteria:

1. All patients with histologically or cytologically confirmed relapsed or refractory AML
[except acute promyelocytic leukemia]; relapsed disease or refractory (refractory to a
non-high-dose cytarabine-containing regimen only); receiving 1st, 2nd or 3rd salvage;
any cytogenetic or molecular abnormality. Patients with secondary AML (after prior
myelodysplasia or therapy for other cancers) will be included.

2. Patients with prior autologous and allogeneic hematopoietic stem cell transplantation
are eligible if patients are off immunosuppression for greater than 14 days and have
no evidence of active graft versus host disease (GVHD) except grade 1 skin GVHD.

3. Clinical laboratory values should be as follows: (a) White blood count < 30,000/µL;
(b) Absolute Blasts in peripheral blood < 20,000 (treatment with Hydroxyurea is
permitted up to 24 hrs prior to LY251092 administration to achieve blast counts <
20,000 prior to enrollment).

4. Patients must be 18-70 years old.

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

6. Patients must have adequate renal function (serum creatinine less than or equal to 1.3
mg/dL). If creatinine is > 1 mg/dL the creatinine clearance should be > 40 mL/min as
calculated using the Cockcroft-Gault formula.

7. Patients must have adequate hepatic function (bilirubin less than or equal to 2.0
mg/dl; serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic
transaminase (SGPT) less than or equal to 3 X the upper limit of normal [ULN] for the
reference lab unless due to leukemia or congenital hemolytic disorder or bilirubin
excretion disorder). 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 Principal Investigator and appropriate dose adjustments will be
considered.

8. Patients must have normal cardiac ejection fraction (left ventricular ejection
fraction [LVEF] greater than or equal to 50%).

9. 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.

10. Negative urine or blood pregnancy test for women of childbearing potential.

11. 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 with untreated or uncontrolled life-threatening infection.

2. Patients who have received chemotherapy and/or radiation therapy within 2 weeks unless
there is evidence of rapidly progressive disease. In the event that subjects have
received chemotherapy < 2 weeks from the date of enrollment, they may be included
provided they have recovered from the associated non-hematological toxicities to less
than or equal to grade 1. Hydroxyurea is allowed up to 24 hours prior to starting
therapy in the setting of rapidly proliferating disease.

3. Patients who have received an investigational anti-cancer drug within two weeks (or
five half-lives, whichever is shorter) of LY251092 administration.

4. History of myocardial infarction or cerebrovascular accident within 6 months of
enrollment date.

5. History of another malignancy. Exception: Patients who have been disease-free for 3
years, or patients with a history of completely resected non-melanoma skin cancer
and/or patients with indolent secondary malignancies, are eligible.

6. Any other medical condition, including mental illness or substance abuse, deemed by
the Investigator 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.

7. Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression
(patients with controlled central nervous system (CNS) disease, i.e. asymptomatic and
currently receiving concurrent intrathecal chemotherapy, are eligible upon discussion
with the Principal InvestigatorI).

8. Known active Hepatitis B Virus (HBV), Human Immunodeficiency Virus (HIV) or Hepatitis
C Virus (HCV) infection (patients with chronic or cleared HBV and HCV infection, are
eligible).