Myelodysplastic Syndrome MedDRA version: 21.1 Level: PT Classification code 10028533 Term: Myelodysplastic syndrome System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Rigosertib
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Rigosertib sodium
CAS Number: 592542-59-1
Other descriptive name: ON 01910.NA
Concentration uni
Sponsors
Onconova Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a. 18-81 years of age; b. Disease classification and cytogenetics confirmed within 8 weeks prior to or during screening as follows: • RAEB-1 per World Health Organization (WHO) MDS criteria (5% to =65 years) yes F.1.3.1 Number of subjects for this age range 320
Exclusion criteria
Exclusion criteria: a. Previous participation in a clinical study of IV or oral rigosertib; patients who failed screening for other rigosertib studies may be screened for participation in this study b. Eligible to receive induction chemotherapy, such as 7-10 days of cytosine arabinoside and 2-3 days of an anthracycline, or high-dose cytarabine (HDAC) c. Patients previously diagnosed with AML (defined as a bone marrow or peripheral blood blast percentage of >30%) d. Suitable candidate to receive allogeneic stem cell Transplantation; Patient is eligible for study if a suitable candidate refuses to undergo an allogeneic stem cell transplant or a suitable donor cannot be found. e. Any active malignancy within the past year, except basal cell or squamous cell skin cancer or carcinoma in situ that is unlikely to progress in two years f. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure or unstable angina pectoris g. Active infection not adequately responding to appropriate therapy h. Total bilirubin =1.5 mg/dL not related to hemolysis or Gilbert’s disease i. Alanine transaminase (ALT)/aspartate transaminase (AST) =2.5 x upper limit of normal (ULN) j. Serum creatinine =2.0 mg/dL or calculated eGFR (estimated Glomerular Filtration Rate) < 40mL/min k. Known active HIV, hepatitis B or hepatitis C, where active is defined as follows: a) HIV or Hepatitis C - presence of viral load b) Hepatitis B - antigen positive l. Uncorrected hyponatremia (defined as serum sodium value of <130 mEq/L) m. Female patients of child-bearing potential (pre-menopausal and not surgically sterilized), who are breast-feeding or have a positive blood beta-human chorionic gonadotropin (ß-HCG) pregnancy test at Screening n. Female patients of child-bearing potential and male patients with sexual 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. Examples of acceptable contraception methods include: - estrogen-gestagen based contraceptives associated with Inhibition of ovulation (oral, intravaginal, transdermal), - gestagen-only based contraceptives associated with inhibition of ovulation (oral, injectable, implantable), - intra-uterine devices (IUDs), - intra-uterine hormone-releasing Systems (IUSs), - bilateral tubal occlusion - vasectomized Partner - sexual abstinence in accordance with an individual's lifestyle o. Major surgery without full recovery or major surgery within 3 weeks before planned randomization p. Uncontrolled hypertension q. New onset seizures (within 3 months before planned randomization) or poorly controlled seizures r. Any other concurrent investigational agent or chemotherapy, radiotherapy, immunotherapy, or corticosteroids (prednisone up to 20 mg/day or its equivalent is permitted for chronic conditions) s. Treatment with cytarabine at any dose, lenalidomide, or any other therapy targeted to the treatment of MDS (other than growth factors and other supportive care measures) within 4 weeks of planned randomization t. Investigational therapy within 4 weeks of planned randomization u. Psychiatric illness or social situation that would limit the patient’s ability to tolerate and/or comply with study requirements.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is: • to compare the overall survival (OS) of patients in the rigosertib group vs the Physician`s Choice group, in all patients and in a subgroup of patients with IPSS-R (Revised International Prognostic Scoring System) very high risk. ;Secondary Objective: • To compare rigosertib to Physician`s Choice with regard to the following: o Overall survival of patients with monosomy 7 chromosomal aberrations o Overall survival of patients with trisomy 8 chromosomal aberrations o Overall response according to 2006 International Working Group (IWG) criteria o Quality-of-life (QoL) scores using the EuroQol EQ-5D Questionnaire o Overall bone marrow blast response according to 2006 IWG criteria o Hematologic improvement (HI) (erythroid, platelet or neutrophil response) according to 2006 IWG criteria ;Primary end point(s): The primary efficacy endpoints are overall survival of all randomized patients (ITT population), and overall survival of patients scored as IPSS-R very high risk.;Timepoint(s) of evaluation of this end point: at each individual patient's death | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall survival of patients with monosomy 7 chromosomal aberrations • Overall survival of patients with trisomy 8 chromosomal aberrations • Overall response rate according to 2006 IWG criteria • Quality-of-life scores using the EuroQol EQ-5D Questionnaire • Overall Bone marrow blast response rate according to 2006 IWG criteria • Hematologic improvement (erythroid, platelet, or neutrophil Response rates) according to 2006 IWG criteria. • Worst-grade adverse events (AEs) • Deaths, other serious AEs, and other AEs leading to discontinuation of study treatment • Worst-grade laboratory abnormalities;Timepoint(s) of evaluation of this end point: not applicable | — |
Countries
Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Croatia, Czech Republic, Estonia, France, Germany, Hungary, India, Ireland, Israel, Italy, Japan, Netherlands, Poland, Russian Federation, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States
Contacts
Public ContactEdgar Fenzl
FGK Representative Service B.V.
Outcome results
None listed