Single-Arm Study of the Efficacy and Safety of Oral Rigosertib in Patients With Myelofibrosis (MF) and Anemia
Condition: Leukemia; Myelofibrosis; Anemia; Splenomegaly
MeSH terms: Anemia; Primary Myelofibrosis; Splenomegaly
Intervention: Rigosertib; Questionnaire
Intervention description: Participants take 560 mg Rigosertib by mouth in the morning (two 280 mg capsules) and 560 mg Rigosertib in the afternoon.; Quality of life questionnaire completed on Day 1 of Cycle 1. It should take about 10-15 minutes to complete.
Intervention MeSH terms: ON 01910
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Leukemia; Myelofibrosis; MF; Anemia; Splenomegaly; Post-polycythemia vera MF; post-PV; post-essential thrombocythemia MF; post-ET; Rigosertib; ON 01910.Na; Questionnaire; Survey

Summary:

      The goal of this clinical research study is to learn if rigosertib can help to control MF in
      patients with anemia. The safety of this drug will also be studied.

      This is an investigational study. Rigosertib 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 35 participants will be enrolled in this study. All will be enrolled at MD Anderson.
    

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.