Three Dosing Schedules of Oral Rigosertib in MDS Patients

• Status: Withdrawn
• Trial end date: 2019-11-01
• Target enrollment: 0
• Participant gender: All

Summary

This study will compare the dosing regimen of oral rigosertib, which has been used in other studies of lower risk Myelodysplastic Syndrome (MDS), with 2 new dosing regimens to determine if one of the new regimens gives improved results as measured by disease status, side effects, and analyses of blood and urine samples.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

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

Criteria

Inclusion Criteria:

• Diagnosis of MDS according to World Health Organization (WHO) criteria or French-American-British (FAB) classification that must be confirmed by bone marrow (BM) aspirate and/or biopsy within 6 weeks prior to Screening.

• MDS classified as Low-risk or Int-1 risk or Int-2 risk according to International Prognostic Scoring System (IPSS) classification; in addition, patients should never have been classified as High-risk since their MDS was diagnosed.

• Transfusion dependency defined by transfusion of at least 4 units of RBC (red blood cells) within 8 weeks before Screening; pre-transfusion Hgb (hemoglobin) values must be ≤ 9 g/dL to be taken into account.

• Refractory to 8- to 12-week course of ESA (erythropoiesis stimulating agent) 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 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 the protocol.

• The patient must signed an informed consent form (ICF).

Exclusion Criteria:

• Ongoing clinically significant anemia due to factors such as iron, vitamin B12, or folate deficiencies, auto-immune or hereditary hemolysis, or gastrointestinal 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.

• 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 of child-bearing potential or male patients with partners of child-bearing potential who are unwilling to follow strict contraception requirements before entry and throughout the study, up to and including the 30-day non-treatment follow-up period.

• Female patients with reproductive potential who do not have a negative blood or urine pregnancy test at Screening or who are lactating.

• 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 chemotherapy, radiotherapy, or immunotherapy.

• Chronic use (˃ 2 weeks) of corticosteroids (˃ 10 mg/24 hour equivalent prednisone) within 4 weeks of Baseline/Cycle 1 Day 1 visit.

• 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.