Phase 2 LCL-161 in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF) or Post-Essential Thrombocytosis Myelofibrosis (Post-ET MF)

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take LCL161 by mouth on
Days 1, 8, 15, and 22 of each cycle, +/- 3 days. You will fast for 2 hours before and 2 hours
after taking LCL161. This means you will have no food during this time. You will be able to
have about 8 ounces of fluids such as water, milk, or non-citrus juices.

Each cycle is 28 days.

If you vomit a dose of LCL161, do not make up the dose.

On Day 1 of Cycle 1, you will take your first dose of study drug at the clinic. You will stay
at the clinic for 4 hours after your first dose of study drug.

After your first dose, you will take the study drug at home. You should bring any unused
study drug with you to each study visit. It is very important that you take the study drug
just as the doctor tells you to. Do not miss any tablets.

If the doctor thinks it is needed, you will be given standard drugs to help decrease the risk
of side effects. You may ask the study staff for information about how the drugs are given
and their risks.

Study Visits:

On Day 1 of Cycle 1, you will have a physical exam, if you have not had a screening physical
exam within 3 days of Day 1 of Cycle 1.

On Day 1 of Cycles 2, 3, 4, 7 and 10, and then every 6 cycles (Cycle 16, 22 etc.) thereafter
while participating in the study:

- You will have a physical exam

- Blood (about 2-3 teaspoons) will be drawn for routine tests.

- If your doctor thinks it is needed, urine will be collected for routine tests.

- You will complete the symptom questionnaires.

If your doctor agrees, you may have your blood drawn at your local doctor's office or
laboratory. You will not have to fill out the questionnaires at your local doctor's office.
The study staff will also call you every 4-6 weeks. You will be asked how you are feeling and
about any side effects you may be having. This phone call and/or email should take about
10-15 minutes. You will return to MD Anderson at the start of Cycles 1, 2, 3, 4, 7, and 10,
and every 6 months thereafter while participating in the study.

On Day 1 of Cycle 4 and then every 6 cycles (Cycles 10, 16, and so on), you will have a bone
marrow biopsy and/or aspirate to check the status of the disease and for cytogenetic testing.

If the doctor thinks it is needed, you may be asked to return to the clinic more often.

Length of Treatment:

You may continue taking the study drug for as long as the doctor thinks it is in your best
interest. 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 call.

End-of-Treatment Visit:

Within 7 days after you are finished taking the study drug:

- You will have a physical exam.

- Blood (about 2-3 teaspoons) will be drawn for routine tests.

- You will complete the symptom questionnaires.

Follow-up Call:

About 30 days after the end-of-treatment visit, the study staff will call you to ask how you
are feeling and about any side effects you may be having. This phone call and/or email should
take about 10-15 minutes.

This is an investigational study. LCL161 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 50 participants will be enrolled in this study. All will take part at MD Anderson.

Inclusion Criteria:

1. Patients must provide written informed consent.

2. Age 18 years or older.

3. Willing and able to comply with scheduled visits, treatment plan and laboratory tests

4. Patient is able to swallow and retain oral medication

5. Must be diagnosed with treatment requiring PMF or post ET/PV MF with intermediate-1,
intermediate -2 or high risk disease according to the IWG prognostic scoring system,
or if with low risk disease then with symptomatic splenomegaly that is >/=5 cm below
left costal margin by physical exam.

6. Patients who are not candidates for, intolerant, or relapsed/refractory to Ruxolitinib

7. ECOG performance status 0-2

8. Required baseline laboratory status: Absolute neutrophil count (ANC) >/= 0.5 x 109/L
(1500/mm3); Serum direct bilirubin and ALT (SGPT) must have AST and ALT
9. Treatment-related toxicities from prior therapies must have resolved to Grade
10. At least 2 weeks from prior MF-directed treatment (till the start of study drug)

Exclusion Criteria:

1. Any concurrent severe and/or uncontrolled medical conditions that could increase the
patient's risk for toxicity while in the study or that could confound discrimination
between disease- and study treatment-related toxicities.

2. Impaired cardiac function or clinically significant cardiac diseases, including any of
the following: History or presence of ventricular tachyarrhythmia; Presence of
unstable atrial fibrillation (ventricular response > 100 bpm). Patients with stable
atrial fibrillation are eligible, provided they do not meet any of the other cardiac
exclusion criteria. Clinically significant resting bradycardia (< 50 bpm). Angina
pectoris or acute myocardial infarction Other clinically significant heart disease (e.g., symptomatic congestive heart
failure; uncontrolled arrhythmia or hypertension; history of labile hypertension or
poor compliance with an antihypertensive regimen).

3. Patients who are currently receiving chronic (>14 days) treatment with corticosteroids
at a dose >/= 10 mg of prednisone (or its glucocorticoid equivalent) per day, or any
other chronic immunosuppressive treatment that cannot be discontinued prior to
starting study drug

4. Patients who are currently receiving treatment with agents that are metabolized solely
through CYP3A4/5 and have a narrow therapeutic index or are strong CYP2C8 inhibitors;
or are receiving treatment with agents that carry a risk for QT prolongation and are
CYP3A substrates.

5. Patients with impairment of GI function or GI disease that may significantly alter the
absorption of LCL161 as per physicians opinion

6. Pregnant or breast feeding (lactating) women, where pregnancy is defined as the state
of a female after conception and until the termination of gestation, confirmed by a
positive beta-HCG laboratory test.

7. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during dosing and for 90 days after study treatment. Highly effective contraception
methods include: Total abstinence or Male partner or female sterilization or
Combination of any two of the following (a+b or a+c, or b+c): a. Use of oral, injected
or implanted hormonal methods of contraception, b. Placement of an intrauterine device
(IUD) or intrauterine system (IUS), c. Barrier methods of contraception: condom for
male partner or occlusive cap (diaphragm or cervical/vault caps) with spermicidal
foam/gel/film/cream/vaginal suppository.

8. Continued from #7 above: Note: Postmenopausal women are allowed to participate in this
study. Women are considered post-menopausal and not of child bearing potential if they
have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical
profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical
bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six
weeks ago. In the case of oophorectomy alone, a woman is considered to be of not child
bearing potential only when her reproductive status has been confirmed by follow-up
hormone level assessment.

9. Sexually active males must use a condom during intercourse while taking the drug and
for 3 months after stopping study drug and should not father a child in this period. A
condom is required to be used also by vasectomized men in order to prevent delivery of
the drug via seminal fluid.