Single-Arm Study of the Efficacy and Safety of Oral Rigosertib in Patients With Myelofibrosis (MF) and Anemia

This is an interventional treatment trial for Leukemia focused on measuring Leukemia, Myelofibrosis, MF, Anemia, Splenomegaly, Post-polycythemia vera MF, post-PV, post-essential thrombocythemia MF, post-ET, Rigosertib, ON 01910.Na, Questionnaire, Survey Read More

Inclusion Criteria:

1. >/= 18 years of age;
2. 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);
3. 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.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2;
5. 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);
6. 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:

1. 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;
2. Serum ferritin < 50 ng/mL;
3. 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.
4. Uncontrolled intercurrent illness, including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia;
5. Active infection not adequately responding to appropriate therapy;
6. Direct bilirubin >/= 2.0 mg/dL not related to hemolysis or Gilbert's disease;
7. Alanine transaminase (ALT) or aspartate transaminase (AST)>/= 2.5 x the upper limit of normal (ULN);
8. Serum creatinine >/= 2.5 mg/dL;
9. Ascites requiring active medical management including paracentesis;
10. Hyponatremia (defined as serum sodium level < 130 mEq/L);
11. Female patients who are pregnant or lactating;
12. 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;
13. Female patients of childbearing potential who have a positive blood or urine pregnancy test at Screening;
14. Major surgery without full recovery or major surgery within 3 weeks of Screening;
15. Uncontrolled hypertension (defined as a sustained systolic pressure >/= 160 mmHg and/or a diastolic pressure >/= 110 mmHg);
16. New onset seizures (within 3 months prior to Screening) or poorly controlled seizures;
17. Any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy;
18. Chronic use (> 2 weeks) of corticosteroids (prednisone >/= 10 mg/24 hr equivalent) within 4 weeks of Screening;
19. Investigational therapy within 2 weeks of Screening;
20. Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements.