Clinical trial NCT02730884 (phase 2, status: terminated)
Conditions: leukemia, myelofibrosis, anemia, splenomegaly
ICD codes: C95.91, C95.92, Z80.6, Z85.6, C90.11, C90.12, C91.01, D75.81, C94.41, C94.42, C94.40, D53.2, D64.9, D46.4, D53.0, D53.9, D61.3, D61.9, D73.81, D73.2, R16.1, R16.2
Drugs: rigosertib
SMILES: COC1=CC(OC)=C(\C=C\S(=O)(=O)CC2=CC=C(OC)C(NCC(O)=O)=C2)C(OC)=C1
Reason stopped: 
    terminated per pis request due to low accrual
  
Eligibility criteria:

        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.