Study of Palbociclib Alone and in Combination in Patients With Relapsed and Refractory (R/R) Leukemias

Study Arms:

If you are found to be eligible to take part in this study, you will be assigned to a study
Arm based on what the study doctor thinks is in your best interest.

- If you are in Arm A, you will receive palbociclib alone in Cycle 1. Beginning in Cycle 2
you will receive palbociclib and sorafenib.

- If you are in Arm B, you will receive palbociclib alone in Cycle 1. Beginning in Cycle 2
you will receive palbociclib and decitabine.

- If you are in Arm C, you will receive palbociclib alone in Cycle 1. Beginning in Cycle 2
you will receive palbociclib and dexamethasone.

Up to 3 dose levels of sorafenib will be tested in Arm A. Up to 3 dose levels of decitabine
will be tested in Arm B. Up to 3 dose levels of dexamethasone will be tested in Arm C. Up to
6 participants will be enrolled at each dose level. The first group of participants will
receive the lowest dose level. Each new group will receive a higher dose than the group
before it, if no intolerable side effects were seen. This will continue until the highest
tolerable doses of sorafenib, decitabine, and dexamethasone are found.

All patients in all 3 arms will receive palbociclib at the same dose.

Study Drug Administration:

There are 28 days in each study cycle.

If you are in Arm A, you will take palbociclib alone by mouth 1 time each day on Days 1-28 of
Cycle 1. Beginning in Cycle 2, you will continue to take palbociclib on Days 1-28 of each
cycle, you will also take sorafenib by mouth on Days 1-28 of each cycle.

If you are in Arm B, you will take palbociclib alone by mouth 1 time each day on Days 1-28 of
Cycle 1. In Cycle 2, you will take palbociclib on Days 1-7 and you will receive decitabine by
vein over about 1 hour on Days 8-17. Beginning in Cycle 3, you will take palbociclib on Days
1-7 of each cycle and you will receive decitabine by vein over about 1 hour on Days 8-12 of
each cycle.

If you are in Arm C, you will take palbociclib alone by mouth 1 time each day on Days 1-28 of
Cycle 1. Beginning in Cycle 2, you will continue to take palbociclib on Days 1-28 of each
cycle and you will take dexamethasone either by mouth or by vein over about 15-30 minutes on
Days 1-4 and Days 15-18 of each cycle.

Length of Study Participation:

You may continue receiving the study drug(s) for up to 8 cycles. You will no longer be able
to take the study drug(s) 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 your last dose of study drug(s).

Study Visits:

Within 3 days before each cycle, you will have a physical exam.

At the start of Cycle 1, you will have an EKG.

At least 1 time each week, blood (about 1 tablespoon) will be drawn for routine tests. If the
disease appears to be going away, this will be done every 2-4 weeks while you are receiving
the study drug.

On Day 28 (+/- 7 days) of Cycles 1 and 2, you will have a bone marrow aspiration and/or
biopsy to check the status of the disease. You may need to have these more frequently if the
study doctor thinks it is needed.

Follow-Up:

After you stop receiving the study drug(s), you may have follow-up visits. These will depend
on what the study doctor thinks is in your best interest.

Inclusion Criteria:

1. Patients with a diagnosis of histologically confirmed relapsed or refractory (R/R)
acute myeloid leukemia or R/R acute lymphoblastic leukemia for which no available
standard therapies are indicated or anticipated to result in a durable response.

2. Only patients with R/R ALL will be eligible for cohort C

3. Age >/= 15 years.

4. Patients must not have had leukemia therapy for 14 days prior to starting palbociclib.
However, patients with rapidly proliferative disease may receive hydroxyurea as needed
until 24 hours prior to starting therapy on this protocol and starting the first cycle
of study.

5. Adequate organ function as defined below: liver function (bilirubin and/or ALT function (creatinine or = 45%
within the past 3 months.

6. ECOG performance status of
7. A negative urine pregnancy test is required within 1 week for all women of
childbearing potential prior to enrolling on this trial.

8. Patient must have the ability to understand the requirements of the study and signed
informed consent. A signed informed consent by the patient or his legally authorized
representative is required prior to their enrollment on the protocol.

Exclusion Criteria:

1. Pregnant women are excluded from this study because the agent used in this study has
the potential for teratogenic or abortifacient effects. Because there is a potential
risk for adverse events in nursing infants secondary to treatment of the mother with
the chemotherapy agents, breastfeeding should also be avoided.

2. Uncontrolled intercurrent illness including, but not limited to active uncontrolled
infection, symptomatic congestive heart failure (NYHA Class III or IV), unstable
angina pectoris, clinically significant cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with study requirements.

3. Patient with documented hypersensitivity to any of the components of the therapy
program.

4. Patients with active, uncontrolled CNS leukemia will not be eligible.

5. Men and women of childbearing potential who do not practice contraception. Women of
childbearing potential and men must agree to use contraception prior to study entry
and for the duration of study participation.

6. Patients with known history of serous retinopathy will not be eligible.

7. Prior treatment with palbociclib