Intervention: Rigosertib
Trial phase: Phase 2
SMILES: COc1cc(OC)c(/C=C/S(=O)(=O)Cc2ccc(OC)c(NCC(=O)O)c2)c(OC)c1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 3
Group description: Participants receive oral Rigosertib under fasting conditions twice a day on a continuous basis. Quality of life questionnaire completed on Day 1 of Cycle 1.

Rigosertib: Participants take 560 mg Rigosertib by mouth in the morning (two 280 mg capsules) and 560 mg Rigosertib in the afternoon.

Questionnaire: Quality of life questionnaire completed on Day 1 of Cycle 1. It should take about 10-15 minutes to complete.
Eligibility criteria:
Inclusion Criteria:

>/= 18 years of age;
Diagnosis of primary myelofibrosis (PMF) or post-polycythemia vera (post-PV) MF or post-essential thrombocythemia (post-ET) MF based on the World Health Organization (WHO) criteria or the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria, which must be confirmed by BM aspirate and/or biopsy within 6 weeks prior to Screening. Measurement of JAK2 V617F allele burden in Bone Marrow (BM) samples, if not done within 6 months prior to Screening, must be provided with the Screening BM biopsy/aspirate report (patients are eligible regardless of JAK2 mutation status);
Anemia or RBC-transfusion dependence defined as follows: a) Anemia: defined for the purpose of this protocol as 1) a hemoglobin level <10 g/L on every determination over 84 days before study-entry, without red blood cell (RBC)-transfusions, or 2) a hemoglobin level <10 g/L on a patient that is receiving RBC-transfusions periodically but not meeting criteria for transfusion-dependent patient as defined below. The baseline hemoglobin value for these subjects is the lowest hemoglobin level during the antecedent 84 days; b) RBC-transfusion-dependence: RBC-transfusion-frequency of >/=2 units packed red blood cells (PRBC)/28 days averaged over 84 days immediately pre-study-entry. There must not be any consecutive 42 days without an RBC-transfusion during this interval.
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2;
Willing to adhere to the prohibitions and restrictions specified in this protocol (Notation: the subject's willingness to adhere to prohibitions and restrictions must be clearly communicated in the on-study note);
The patient must signed an informed consent form (ICF) indicating that s/he understands the purpose of, and procedures required for, the study and is willing to participate.

Exclusion Criteria:

Ongoing clinically significant anemia due to factors such as known iron, vitamin B12, or folate deficiencies, auto-immune or hereditary hemolysis, or gastrointestinal (GI) bleeding;
Serum ferritin < 50 ng/mL;
Any active malignancy within the past year, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast; patients with history of prior malignancies should be free of disease for at least 3 years to be eligible for this study.
Uncontrolled intercurrent illness, including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia;
Active infection not adequately responding to appropriate therapy;
Direct bilirubin >/= 2.0 mg/dL not related to hemolysis or Gilbert's disease;
Alanine transaminase (ALT) or aspartate transaminase (AST)>/= 2.5 x the upper limit of normal (ULN);
Serum creatinine >/= 2.5 mg/dL;
Ascites requiring active medical management including paracentesis;
Hyponatremia (defined as serum sodium level < 130 mEq/L);
Female patients who are pregnant or lactating;
Patients of childbearing potential (ie, women of childbearing potential and men with female partners of childbearing potential) who are unwilling to follow strict contraception requirements (including 2 reliable methods in combination: 1 non-hormonal, highly-reliable method [diaphragm, condoms with spermicidal foam or jelly, or sterilization] plus 1 additional reliable method [birth control pills, intrauterine device, contraceptive injections, or contraceptive patches]) before entry and throughout the study, up to and including the 30-day non-treatment follow-up period;
Female patients of childbearing potential who have a positive blood or urine pregnancy test at Screening;
Major surgery without full recovery or major surgery within 3 weeks of Screening;
Uncontrolled hypertension (defined as a sustained systolic pressure >/= 160 mmHg and/or a diastolic pressure >/= 110 mmHg);
New onset seizures (within 3 months prior to Screening) or poorly controlled seizures;
Any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy;
Chronic use (> 2 weeks) of corticosteroids (prednisone >/= 10 mg/24 hr equivalent) within 4 weeks of Screening;
Investigational therapy within 2 weeks of Screening;
Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements.