Granulocyte-colony Stimulating Factor (G-CSF) and Plerixafor Plus Sorafenib for Acute Myelogenous Leukemia (AML) With FLT3 Mutations

The Study Drugs:

Sorafenib is a type of drug called a multikinase inhibitor. It is designed to interfere with
the parts of cancer cells that are involved in the sending of chemical messages and helping
the cells divide and grow, which may block the formation of tumors and cause cell death.

Filgrastim promotes the growth of white blood cells, which help to fight infections.

Plerixafor is designed to help move stem cells from the bone marrow to the blood.

Study Drug Dose Level:

If participant is found to be eligible to take part in this study, they will be assigned to
a dose level and schedule of sorafenib based on when they joined this study. Up to 5 dose
levels and schedules will be tested. Three (3) participants will be enrolled at each dose
level for Phase I of the study. The first group of participants will receive dose level "0"
of sorafenib. If unacceptable side effects are seen, a dose lower than level "0" will be
tried. If no side effects are seen, the next group of 3 participants will be placed on a
higher dose level, called Level "1." Each new group will either receive a higher or lower
dose of sorafenib or take it more or less often than the group before it, based on whether
intolerable side effects are seen. This will continue until the best tolerable dose and
schedule of sorafenib is found. Once the best tolerable dose and/or schedule is found, the
last 10 participants will be enrolled and will take sorafenib at that dose and schedule.
This last group of 10 is considered the early Phase II part of the study.

Each group will receive the same dose level and schedule of filgrastim and plerixafor.

Study Drug Administration:

Participant will receive filgrastim and plerixafor by injection through a needle under the
skin on Day 1 (the day the study starts) and then every other day for a total of 7 doses.
The injections will be given in the morning. After day one, the injections may be done at
participant's home. Participant's study doctor will meet with them one-on-one to discuss how
the drug will be given.

On Day 1, participant will begin taking their dose of sorafenib by mouth every other day,
once a day, or twice a day, depending on when they join the study.

- If participant is taking sorafenib every other day, during Cycle 1 they will start
taking it 12 hours after the filgrastim and plerixafor injections (the next morning) .

- If participant is taking sorafenib every day, they will take it at the same time every
morning. The first time participant takes sorafenib during Cycle 1 will be 12 hours
after the first filgrastim and plerixafor injections.

- If participant is taking sorafenib twice a day, during Cycle 1 they will start taking
it 12 hours after the filgrastim and plerixafor injections and then every 12 hours.

Participant will take sorafenib without food, at least 1 hour before or 2 hours after
eating. If participant misses a dose, they should not take double the dose next time to make
up for the missed dose.

These 28 days are one "study cycle".

Participant is allowed to take hydroxyurea or other treatments to control high white blood
cell counts.

Study Drug Diary:

Participant will be given a study drug diary that they will be expected to fill out whenever
they take study drugs at home. A staff member will explain to participant how to fill out
the diary. The study staff will review the diary with participant at every study visit and
they will be given a new diary at the beginning of every cycle they start.

Study Visits:

Every week for the first 6 weeks and then every 4-8 weeks until participant leaves the
study, the following tests and procedures will be performed:

- Participant will have a physical exam, including measurement of their weight, and vital
signs.

- Participant will have a bone marrow aspiration and biopsy done before treatment starts
and once somewhere between day 14 and day 17 after the first Sorafenib administration.
Another bone marrow sample will be collected between days 24 and 28.

- If participant continues on study, another bone marrow sample will be collected after
the third cycle.

- Blood (about 1 teaspoon) will be drawn every 2-4 days for routine tests while
participant is taking the study drugs and once a week on days they are not taking the
study drugs Plerixafor and Neupogen.

- During the first week, blood (about 1 teaspoon) will be drawn to check the status of
the disease before each dose of the filgrastim and plerixafor combination and again 4
to 8 hours after receiving the study drugs. If participant's doctor feels it is needed,
additional blood may be drawn after the 2nd blood draw to check the status of the
disease. If participant's doctor feels it is needed, these blood draws may continue
after the first week if the disease is not responding.

Length of Study:

Participant may continue taking the study drugs for up to 6 cycles (about 6 months). If
participant is in complete remission, partial remission, or complete remission with
incomplete platelet count recovery after 6 months with no intolerable side effects, their
doctor may discuss continuing on the study with them. Participant will be taken off study if
the disease gets worse or intolerable side effects occur.

Follow-up Visits:

If participant is in complete remission, and if their doctor thinks it is in their best
interest, they may have follow-up visits about every 3 months until the study closes.

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

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

End-of-Study Visit:

Participant will have an end-of-study visit about 30 days after their last dose of the study
drugs. At this visit, the following tests and procedures will be performed:

- Participant will have a physical exam, including measurement of their weight and vital
signs.

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

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

This is an investigational study. Sorafenib is FDA-approved and commercially available for
treatment of advanced renal cell cancer (RCC) and hepatocellular cancer (HCC) that cannot be
removed by surgery. Its use in patients with AML is investigational.

Plerixafor is FDA-approved and commercially available for use in boosting the number of
hematopoietic stem cells (HSC) for stem cell collection and transplants (in combination with
filgrastim) in participants with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Its
use in participants with AML is investigational.

Filgrastim (NeupogenÒ) is FDA-approved and commercially available for use in boosting white
blood cell production in participants with low blood cell counts caused by chemotherapy
(nonmyeloid malignancies, acute myeloid leukemia, and bone marrow transplantation), treating
severe chronic neutropenia (SCN-low blood counts), and boosting production of hematopoietic
progenitor cells in patients undergoing peripheral blood progenitor cell (PBPC) collection.

Up to 28 participants will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patients will be 18 years of age or older.

2. Patients must have relapsed/refractory leukemia with FLT3 (ITD) mutations. Patients
with AML FLT3 mutations who are not eligible for frontline standard therapy, or who
refuse to be treated with intensive chemotherapy, may be eligible.

3. Serum biochemical values with the following limits unless considered due to leukemia:
creatinine hemolysis or congenital disorder; or transaminases (SGPT)
4. Able to take oral medication.

5. Able to understand and provide signed informed consent.

6. Ejection fraction at screening must be >/=50%.

7. Performance status < 3, unless directly related to leukemic disease process as
determined by the Principal Investigator.

Exclusion Criteria:

1. Subjects with acute promyelocytic leukemia.

2. Patients with absolute blast count > 20 k/uL.

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, IUD, diaphragm, abstinence, or condoms by
their partner) over the entire course of the study.

4. Men not willing to maintain adequate contraception with their partner over the entire
course of the study.

5. Hypertension > 140 mmHg systolic OR > 90 mmHg diastolic with or without
antihypertensive therapy.

6. Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have
unstable angina (anginal symptoms at rest) or new onset angina (began within the last
3 months) or myocardial infarction within the past 6 months.

7. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy. Sorafenib is
contraindicated in patients with known severe hypersensitivity to sorafenib or any of
the excipients.

8. Known human immunodeficiency virus (HIV) infection or active Hepatitis B or C.

9. Thrombotic or embolic events such as a cerebrovascular accident including transient
ischemic attacks within the past 6 months.

10. Pulmonary hemorrhage/bleeding event >/= CTCAE Grade 2 within 4 weeks of first dose of
study drug.

11. Any other hemorrhage/bleeding event >/= CTCAE Grade 3 within 4 weeks of first dose of
study drug.

12. Major surgery, open biopsy or significant traumatic injury within 4 weeks of first
study drug.

13. Currently using St. John's Wort or rifampin.

14. Known or suspected allergy to sorafenib or any agent given in the course of this
trial.

15. Active clinically serious and uncontrolled infection > CTCAE Grade 2.

16. Serious non-healing wound, ulcer, or bone fracture.

17. Patients currently receiving any other standard or investigational treatment for
their hematologic malignancy.