A Single-arm Study to Assess the Efficacy and Safety of Oral Rigosertib in Transfusion-dependent, Low or Intermediate-1, Myelodysplastic Syndrome Patients Based on the International Prognostic Scoring System

Location:

Rochester, Minn.

Trial status:

Open for Enrollment

Why is this study being done?

This will be a Phase II, single-arm, multicenter study (approximately 15 centers). Up to 40 transfusion-dependent patients with Low- or Int-1 risk MDS by IPSS will be enrolled and treated with 560 mg oral rigosertib BID taken intermittently (2 weeks on/1 week off regimen). Cycles will be 3 weeks in length. Enrollment will proceed as follows: In the first cohort, 6 patients will be enrolled initially. If no more than 1 drug-related Grade 3 toxicity (based on NCI CTCAE) is observed during the first 21-day cycle in the first 6 enrolled patients, 4 additional patients will be enrolled to complete the first cohort. Up to 3 more successive cohorts of 10 patients each will be enrolled, provided there are at least 1 response in the first cohort (10 patients), 4 responses total in the first and second cohorts (20 patients), and 6 responses total in the first, second and third cohorts (30 patients). The study will be stopped if any one of these responses is not met.

Who is eligible to participate?

Inclusion Criteria: - Diagnosis of MDS according to World Health Organization (WHO) criteria (Appendix 2) or French-American-British (FAB) classification that must be confirmed by bone marrow (BM) aspirate and/or biopsy within 6 weeks prior to Screening. - Myelodysplastic syndrome (MDS) classified as Low risk or Int-1 risk, according to International Prognostic Scoring System (IPSS) classification; in addition, patients should never have been classified as Int-2 or High-risk since their MDS was diagnosed; - Transfusion dependency defined by transfusion of at least 4 units of Red blood cells (RBC) within 56 days before Screening (pre-transfusion Hgb values values must be ≤ 9 g/dL to be taken into account). - Refractory to 8- to 12-week course of Erythropoiesis-stimulating agent (ESA) administered within the past 2 years before enrollment, or erythropoietin (EPO) level ˃ 500 mU/mL and off ESA for at least 8 weeks before Screening. - Off all other treatments for MDS (azacitidine, decitabine, lenalidomide, ESA, chemotherapy, immunotherapy) for at least 2 weeks prior to Screening. - Eastern Cooperative Oncology Group(ECOG) performance status of 0, 1 or 2. - Willing to adhere to the prohibitions and restrictions specified in this protocol. - 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 iron, vitamin B12, or folate deficiencies, auto-immune or hereditary hemolysis, or gastrointestinal (GI) bleeding. - Serum ferritin < 50 ng/mL. - Hypoplastic MDS (cellularity <10%) - Any active malignancy within the past year, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast. - 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. - Total 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 ≥ 2.0 mg/dL. - Ascites requiring active medical management including paracentesis. - Hyponatremia (defined as serum sodium value of < 130 mEq/L). - Female patients who are pregnant or lactating. - Patients who are unwilling to follow strict contraception requirements. - Female patients with reproductive potential who do not have a negative urine pregnancy test at Screening. - Major surgery without full recovery or major surgery within 3 weeks of Screening. - Uncontrolled hypertension (defined as a systolic pressure ≥ 160 mmHg and/or a diastolic pressure ≥ 110 mmHg). - New onset seizures (within 3 months prior to the first dose of rigosertib) or poorly controlled seizures. - Any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy. - Chronic use (˃ 2 weeks) of corticosteroids (˃ 10 mg/24 hr equivalent prednisone) within 4 weeks of Screening. - Investigational therapy within 4 weeks of Screening. - Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements.

Last updated:

5/28/2014

NCT ID:

NCT01904682

IRB Number:

13-009041