Myelodysplastic syndrome with excess blasts MedDRA version: 16.1 Level: HLT Classification code 10028536 Term: Myelodysplastic syndromes System Organ Class: 100000004851
Conditions
Interventions
Product Code: ON01910.Na
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: N/A
CAS Number: 592542-60-1
Current Sponsor code: ON 01910.Na
Other descriptive name: Rigoserti
Sponsors
Onconova Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 confirmed within 6 weeks prior to study entry 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 WBC =65 years) yes F.1.3.1 Number of subjects for this age range 135
Exclusion criteria
Exclusion criteria: Patients with any of the following will not be enrolled in the study: a. Anemia due to factors other than MDS (including hemolysis or gastrointestinal [GI] bleeding) unless stabilized for 1 week after RBC transfusion; b. Any active malignancy within the past year, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast; c. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia; d. Active infection not adequately responding to appropriate therapy; e. Total bilirubin =1.5 mg/dL not related to hemolysis or Gilbert’s disease; f. Alanine transaminase (ALT)/aspartate transaminase (AST) =2.5 x upper limit of normal (ULN); g. Serum creatinine =2.0 mg/dL; h. Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of <130 mEq/L); i. Female patients who are pregnant or lactating; j. Patients who are unwilling to follow strict contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine device, double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) before entry and throughout the study; k. Female patients with reproductive potential who do not have a negative urine beta-human chorionic gonadotropin (ßHCG) pregnancy test at screening; l. Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na treatment start; m. Uncontrolled hypertension (defined as a systolic pressure =160 mmHg and/or a diastolic pressure =110 mmHg); n. New onset seizures (within 3 months prior to the first dose of ON 01910.Na) or poorly controlled seizures; o. Any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy; p. Prior treatment with low-dose cytarabine during the past 2 years; q. Investigational therapy within 4 weeks of starting ON 01910.Na; r. 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 the study is to compare overall survival (OS) in patients receiving 1800 mg/24 hr of ON 01910.Na via 72-hour continuous intravenous infusion administered every other week + best supportive care (BSC) to OS of patients receiving BSC in a population of patients with myelodysplastic syndrome with excess blasts (5% to 30% bone marrow blasts) having failed, being intolerant, or progressing after azacitidine or decitabine treatment.;Secondary Objective: Compare the BSC + ON 01910.Na group to the BSC group with respect to: • Overall survival in each of the subsets of patients as defined in the protocol •Overall response (complete + partial remission) according to 2006 IWG criteria • Complete bone marrow response according to 2006 IWG criteria • Hematological improvements in ANC, platelet count, and erythroid responses according to 2006 IWG criteria • Improvements of cytogenetics as evaluated by the change in aneuploidy in bone marrow according to 2006 IWG criteria •Relationship between best BM blast response and OS • Transition time to AML: -Defined for RAEB-1 and RAEB-2 MDS and chronic myelomonocytic leukemia (CMML) patients (with BM blasts from 10% to 20% for CMML) by an increase of at least 50% BM blasts and more than 20% BM blasts -Defined for RAEB-t by an increase of at least 50% BM blasts • Quality-of-life (QOL) scores (using the EORTC Quality of Life Questionnaire [QLQ]-C30 version 3 • Incidence of infections;Primary end point(s): 3.4.2. Efficacy Assessments The following outcomes will be assessed: • Overall survival • Blastic response in BM • Progression to AML defined as: o =50% BM blasts increase and >20% BM blasts for RAEB-1, RAEB-2, and CMML patients o =50% BM blasts increase for RAEB-t patients • Change in BM cytogenetics • Changes in ANC • Changes in platelet count and platelet transfusions requirements • Changes in Hgb and RBC transfusion requirements • QOL questionnaire using EORTC QLQ-C30 version 3 • Incidence | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): None defined;Timepoint(s) of evaluation of this end point: None given | — |
Countries
Belgium, France, Germany, Italy, Spain, United States
Contacts
Public ContactOncology Support Centre
PRA- Pharmaceutical Research Associates
Outcome results
None listed