Pacritinib for Patients With Lower-Risk Myelodysplastic Syndromes (MDS)

Study Drug Administration:

Each cycle is 28 days.

If you are found to be eligible to take part in this study, you will take pacritinib by mouth
2 times each day during Cycles 1-4. Each dose should be about 12 hours apart (1 dose in the
morning, 1 dose in the evening).

After Cycle 4, if the study doctor thinks it is in your best interest, you may be able to
continue taking pacritinib in combination with either azacitidine or decitabine. The study
doctor will tell you which drug you will receive. The study doctor will tell you which drug
you will receive. Decitabine and azacitidine may be administered by local doctor or at MD
Anderson. Cycle 1 of Part 2 will be administered at MD Anderson. Commercial supplies of
decitabine and azacitidine will be used.

You will receive either azacitidine by vein over about 1 hour on Days 1-5 of Cycles 5 and
beyond or decitabine by vein over about 1 hour or as an injection under the skin on Days 1-7
of Cycles 5 and beyond.

You should return any unused study drug and/or any empty bottles to each study visit.

Study Visits:

One (1) time each week during Cycle 1 and then on Day 1 of each cycle after that, blood
(about 1½ teaspoons) will be drawn for routine tests. You may have this blood drawn at a
local lab or clinic closer to your home, if the study doctor thinks this is acceptable. The
results from the blood draw will be sent to the study doctor.

On Day 28 (+/- 5 days) of Cycles 1 and 4, you will have a bone marrow aspiration/biopsy to
check for genetic mutations and cytogenetic testing. If you begin receiving pacritinib in
combination with either azacitidine or decitabine, you will also have this test repeated at
Cycle 4 of your combination therapy.

On Day 1 of Cycle 1, Day 28 of Cycles 1 and 4, and at any time the doctor thinks it is
needed, you will have an EKG.

Length of Treatment:

You may continue taking pacritinib for up to 4 cycles. If the doctor thinks it is in your
best interest, you may be eligible to continue taking the study drug in combination with
either azacitidine or decitabine for as long as the doctor thinks it is in your best
interest.

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 the end-of-treatment visit.

After the end of therapy and/or 30 days after your last dose of study drug, the study staff
will follow your health status by phone call every 2 months (+/- 2 months) until you receive
another cancer treatment.

End-of-Treatment Visit:

About 28 days after the last dose of study drug(s):

- Blood (about 1½ teaspoons) will be drawn for routine tests.

- If the doctor thinks it is needed, you will have a bone marrow aspirate/biopsy to check
the status of the disease.

This is an investigational study. Pacritinib is not FDA approved or commercially available.
It is currently being used for research purposes only. Azacitidine and decitabine are both
FDA approved and commercially available for the treatment of MDS. The study doctor can
explain how the study drugs are designed to work.

Up to 40 participants will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Signed informed consent indicating that patients are aware of the investigational
nature of this study, in keeping with the policies of MD Anderson Cancer Center
(MDACC), must be obtained prior to any study specific procedures.

2. Patients with a histologically confirmed diagnosis of MDS by World Health Organization
(WHO) classification, and lower-risk MDS as defined by the IPSS classification (Low or
Int-1 disease) or R-IPSS classification (Very Low or Low) are eligible. Patients with
MDS/MPD overlap syndromes including CMML are also eligible if they have Low or Int-1
disease per IPSS. Patients may have received MDS-directed therapy (i.e. lenalidomide),
although patients with prior exposure to hypomethylating agents (e.g. 5-azacitidine or
decitabine) are not eligible.

3. The interval from prior treatment to time of study drug administration is at least 1
week (except for hydroxyurea or steroid therapy) with recovery from all prior
therapy-related toxicities

4. Age >/= 18 years old.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

6. Adequate liver function, as evidence by serum bilirubin range (except for patients with Gilbert's Disease) or an aspartate aminotransferase
(AST) or alanine aminotransferase (ALT) of investigator.

7. Serum creatinine (Cr) /=50 ml/min

8. Subjects of reproductive potential must agree to the use of acceptable contraceptive
methods for the duration of the time on study and a further 6 months after completion
of treatment. Women of childbearing potential must have a negative blood or urine
pregnancy test within 72 hours of start of treatment.

Exclusion Criteria:

1. Subjects with any prior exposure to the hypomethylating agents (5-azacitidine or
decitabine) are excluded.

2. Subjects with any prior exposure to JAK2 inhibitor therapy (i.e. ruxolitinib or prior
pacritinib therapy) are excluded.

3. Any prior or coexisting medical condition that in the investigator's judgment will
substantially increase the risk associated with the subject's participation in the
study.

4. Psychiatric disorders or altered mental status precluding understanding of the
informed consent process and/or completion of the necessary study procedures.

5. Active uncontrolled serious infection or sepsis at study enrollment. Patients
receiving antibiotics for infections that are under control may be included in the
study.

6. Gastrointestinal disorders that may significantly interfere with absorption of study
drug.

7. Subjects have received potent CYP3A inhibitors within 7 days prior to the initiation
of study treatment.

8. History of myocardial infarction, severe/unstable angina, or symptomatic congestive
heart failure (New York Heart Failure (NYHA) Class III or IV congestive heart failure)
within 6 months prior to study enrollment or Left ventricular ejection fraction (LVEF)
<50%

9. Impaired cardiac function including ongoing cardiac dysrhythmias of Grade > 2,
ejection fraction < 50%, atrial fibrillation of any grade, or QTc prolongation > 450
ms, or other factors that increase the risk of QT prolongation (i.e. family history of
long QT interval syndrome, hypokalemia defined as serum potassium < 3.0 mEq/L)

10. Diagnosis of other malignancies within the last 3 years other than curatively treated
non-melanoma skin cancer, carcinoma in situ of the cervix, organ-confined or treated
non-metastatic prostate cancer, in situ breast carcinoma after complete surgical
resection, or superficial transitional cell bladder carcinoma.

11. Known active Hepatitis A, B or C.

12. Known HIV seropositivity.

13. Women who are pregnant or lactating.