Myelodysplastic Syndrome MedDRA version: 18.1 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 sodium
Product Code: ON 01910.Na
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Rigosertib sodium
CAS Number: 592542-59-1
Other descriptive na
Sponsors
Onconova Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a. =18 years of age; b. Diagnosis of MDS confirmed within 6 weeks prior to Screening according to WHO criteria or FAB classification; c. MDS classified as follows, according to WHO criteria and FAB classification: • RAEB-1 (5% to 9% BM blasts) • RAEB-2 (10% to 19% BM blasts) • CMML (10% to 20% BM blasts) and white blood cells (WBC) 5% BMBL • For patients with 5-10% BMBL, = 50% increase in BMBL to > 10% BMBL • For patients with 10-20% BMBL, = 50% increase in BMBL to > 20% BMBL • For patients with 20-30% BMBL, = 50% increase in BMBL to > 30% BMBL • Any of the following: - = 50% decrease from maximum remission/response levels in granulocytes or PLT - Decrease in Hgb concentration by = 2 g/dL - Transfusion dependence, defined as administration of at least 4 RBC units in the past 8 weeks before Screening (patients must have Hgb values =65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: a. Previous participation in a clinical study of IV or oral rigosertib. However, patients who failed screening in pivotal study 04-21 may be screened for participation in this 04-24 study; b. Anemia due to factors other than MDS (including hemolysis or gastrointestinal [GI] bleeding) unless stabilized for 1 week after RBC transfusion; c. Any active malignancy within the past year, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast; d. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia; e. Active infection not adequately responding to appropriate therapy; f. Total bilirubin = 1.5 mg/dL not related to hemolysis or Gilbert’s disease; g. ALT/AST = 2.5 x upper limit of normal (ULN); h. Serum creatinine = 2.0 mg/dL; i. Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of <130 mEq/L); j. Female patients who are pregnant or lactating; k. Female patients of child-bearing potential and male patients with partners of child-bearing potential 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; l. Female patients with reproductive potential who do not have a negative blood or urine beta-human chorionic gonadotropin (ßHCG) pregnancy test at Screening; m. Major surgery without full recovery or major surgery within 3 weeks of Baseline/Cycle 1 Day 1 (C1D1) visit; n. Uncontrolled hypertension (defined as a systolic pressure =160 mmHg and/or a diastolic pressure = 110 mmHg); o. New onset seizures (within 3 months prior to Baseline/C1D1) or poorly controlled seizures; p. Any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy; q. Prior treatment with low-dose cytarabine during the past 2 years; r. Investigational therapy within 4 weeks of Baseline/C1D1 visit; s. 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 efficacy objective of the study is to evaluate the relationship between best bone marrow blast response and overall survival in MDS patients with excess blasts (5-30%) progressing on or after treatment with azacitidine or decitabine. Bone marrow blast response is defined as BM complete response (BMCR), = 50% BM blast decrease from pretreatment value, or stable BM response (no progression) according to the International Working Group (IWG) 2006 criteria.;Secondary Objective: • Overall response (complete remission [CR], partial remission [PR], bone marrow complete response [BMCR], and stable disease [SD]) according to 2006 IWG criteria; • Hematological improvements (erythroid response [ER], platelet response [PLR] and neutrophil response [NR]) according to 2006 IWG criteria; • Improvements of cytogenetics as evaluated by the change in aneuploidy in BM according to 2006 IWG criteria; • Progression-free survival; • Transition time to AML, where AML is defined as follows: - Increase of at least 50% BMBL, and more than 20% BMBL for RAEB-1 and RAEB-2 and CMML patients; - Increase of at least 50% BMBL for RAEB-t patients; • Quality-of-life (QOL) scores (using EORTC Quality of Life Questionnaire [QLQ]-C30 version 3; • Incidence of infections requiring treatment with IV antimicrobials and of bleeding episodes. • Population pharmacokinetics.;Primary end point(s): • Overall survival, defined as time from first study treatment to death from any cause; • Time to transition to AML; • Change in BM cytogenetics • Changes in ANC, PLT and Hgb values; • Changes in RBC and PLT transfusions requirements; • EORTC QLQ-C30 questionnaire version 3; • Incidence of infections (treated with IV antimicrobials) and bleeding episodes (and their severity); • Best BMBL response defined as BMCR, = 50% BMBL decrease from pretreatment value, or stable BM response (no progression) according to IWG 2006 criteria; • Time to best BMBL response; • Duration of best BMBL response; | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: Not applicable | — |
Countries
Australia, Denmark, France, Germany, Italy, Spain, Sweden, United States
Contacts
Public ContactProject Manager 04-24
Chiltern International Ltd.
Outcome results
None listed