A study to assess the efficacy and safety of oral rigosertib in patients with myelodysplastic syndrome (a blood disease) who are dependent on transfusions.

Conditions: Myelodysplastic Syndrome
MedDRA version: 14.1Level: PTClassification code 10028533Term: Myelodysplastic syndromeSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2013-000672-15-FR

Lead Sponsor: Onconova Therapeutics, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 40

Inclusion Criteria

Male and female patients who meet all of the following criteria are eligible for enrollment in the trial:
a. =18 years of age;
b. Diagnosis of MDS according to World Health Organization (WHO) criteria (Appendix 2) or French-American-British (FAB) classification, that must be confirmed by BM aspirate and/or biopsy within 6 weeks prior to Screening;
c. MDS classified as Low risk or Int-1 risk, according to IPSS classification; in addition, patients should never have been classified as Int-2 or High-risk since their MDS was diagnosed;
d. Transfusion dependency defined by transfusion of at least 4 units of RBC within 56 days (ie, 8 weeks) before Screening (pre-transfusion Hgb values values must be = 9 g/dL to be taken into account);
e. Refractory to 8- to 12-week course of ESA administered within the past 2 years before enrollment, or EPO level > 500 mU/mL and off ESA for at least 8 weeks before Screening;
f. Off all other treatments for MDS (AZA, decitabine, lenalinomide, ESA, chemotherapy, immunotherapy) for at least 2 weeks prior to Screening;
g. ECOG performance status of 0, 1 or 2;
h. Willing to adhere to the prohibitions and restrictions specified in this protocol;
i. The patient must sign an informed consent form (ICF) indicating that s/he understands the purpose of, and procedures required for, the study and is willing to participate.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

Patients with any of the following will not be enrolled in the study:
a. Ongoing clinically significant anemia due to factors such as iron, vitamin B12, or folate deficiencies, auto-immune or hereditary hemolysis, or gastrointestinal (GI) bleeding;
b. Serum ferritin < 50 ng/mL;
c. Hypoplastic MDS (cellularity <10%);
d. Any active malignancy within the past year, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast;
e. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia;
f. Active infection not adequately responding to appropriate therapy;
g. Total bilirubin = 2.0 mg/dL not related to hemolysis or Gilbert’s disease;
h. Alanine transaminase (ALT) or aspartate transaminase (AST) = 2.5 x the upper limit of normal (ULN);
i. Serum creatinine = 2.0 mg/dL;
j. Ascites requiring active medical management including paracentesis;
k. Hyponatremia (defined as serum sodium value of < 130 mEq/L);
l. Female patients who are pregnant or lactating;
m. Patients who are unwilling to follow strict contraception requirements (including 2 reliable methods in combination: one non-hormonal, highly-reliable method [diaphragm, condoms with spermicidal foam or jelly, or sterilization] plus one 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 nontreatment follow-up period;
n. Female patients with reproductive potential who do not have a negative urine pregnancy test at Screening;
o. Major surgery without full recovery or major surgery within 3 weeks of Screening;
p. Uncontrolled hypertension (defined as a systolic pressure = 160 mmHg and/or a diastolic pressure = 110 mmHg);
q. New onset seizures (within 3 months prior to the first dose of rigosertib) or poorly controlled seizures;
r. Any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy;
s. Chronic use (> 2 weeks) of corticosteroids (> 10 mg/24 hr equivalent prednisone) within 4 weeks of Screening;
t. Investigational therapy within 4 weeks of Screening;
u. Psychiatric illness or social situation that would limit the patient’s ability to tolerate and/or comply with study requirements.