Efficacy and Safety of Oral Rigosertib in Transfusion-dependent, Low or Int-1 or Trisomy 8 Int-2 Myelodysplastic Syndrome

• Status: Completed
• Trial end date: 2015-11-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objectives of this study are to determine if rigosertib sodium, given orally in the form of soft gel capsules, is safe and is associated with a reduction in the number of blood transfusion units that are needed in patients with myelodysplastic syndrome (MDS) classified as Low or Intermediate-1 (Int-1) (any cytogenetics) or trisomy 8 Intermediate 2 (Int-2) in the International Prognostic Scoring System (IPSS) who are transfusion-dependent. Rigosertib will be taken on days 1 to 21 of a 21-day cycle.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Onconova Therapeutics, Inc.
• Treatments: Glycine; ON 01910

Criteria

Inclusion Criteria:

• Diagnosis of MDS confirmed by bone marrow aspirate and/or biopsy within 6 weeks prior to first dose of study drug according to World Health Organization (WHO) or French-American-British (FAB) classification

• MDS classified as Low risk or Int-1 risk (any cytogenetics) or Trisomy 8 Int-2 risk, according to IPSS classification

• Transfusion dependency defined by at least 4 units of RBC administered within 8 weeks before baseline

• Off all other treatments for MDS (azacitidine, decitabine, lenalidomide, chemotherapy, immunosuppressive agents) for at least 4 weeks

• ECOG performance status of 0, 1 or 2

Exclusion Criteria:

• Ongoing clinically significant anemia due to factors such as iron, B12, or folate deficiencies, auto-immune or hereditary hemolysis, or gastrointestinal (GI) bleeding, unless stabilized for 1 week after RBC transfusion

• 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 ≥1.5 mg/dL not related to hemolysis or Gilbert's disease

• ALT/AST ≥2.5 x 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 beta-human chorionic gonadotropin (bHCG) pregnancy test at Screening

• Major surgery without full recovery or major surgery within 3 weeks of rigosertib treatment start

• 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 starting rigosertib

• Investigational therapy within 4 weeks of starting rigosertib

• Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements