Health Condition 1: null- Refractory Intermediate 1, Intermediate-2, or High Risk Myelodysplastic Syndrome
Conditions
Interventions
Intervention1: Chemical Name: Sodium salt of (E)-2,4,6-trimethoxystyryl-3-carboxymethylamino-4-methoxybenzyl sulfone
Research No. ON 01910.Na concentrate
: Chemical Name: Sodium salt of (E)-2,4,6-tr
Sponsors
Onconova Therapeutics Inc
Max Neeman International
Eligibility
Inclusion criteria
Inclusion criteria: Inclusion Criteria: 1. ≥ 18 years of age 2. Diagnosis of MDS confirmed within 4 weeks prior to study entry according to the World Health Organization (WHO) Criteria) or the French-American-British (FAB) Classification 3. Intermediate-1 or -2 or High-Risk MDS according to the International Prognostic Scoring System (IPSS) Score 4. At least one cytopenia (Absolute Neutrophil Count 1500/microlitre or Platelet Count 100,000/microlitre or Hemoglobin 10 g/dL) 5. Failure of, or insufficient response to, Azacytidine or Decitabine , or progressive disease (according to IWG 2006 criteria) after treatment with available chemotherapy or best supportive care (BSC) (e.g., transfusions, growth factors, antibiotics, etc.) 6. Failed to respond to, relapsed following, or opted not to participate in bone marrow transplantation 7. Off all other treatments for MDS (including filgrastim [G-CSF] and erythropoietin) for at least 4 weeks (only 2 weeks if PROCRITTM is used). Filgrastim (G-CSF) can be used before, during, and after the protocol treatment for patients with documented febrile neutropenia (500/μL) 8. ECOG Performance Status 0, 1 or 2 9. Willing to adhere to the prohibitions and restrictions specified in this protocol 10. Patient (or his/her legally authorized representative) must have signed an informed consent document indicating that he/she understands the purpose of and procedures required for the study and is willing to participate in the study.
Exclusion criteria
Exclusion criteria: 1. Anemia due to factors other than MDS (including hemolysis or gastrointestinal [GI] bleeding) 2. Hypoplastic MDS (cellularity 10%) 3. Any active malignancy within the past year, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast 4. HIV-1 seropositivity 5. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia 6. Active infection not adequately responding to appropriate therapy 7. Total bilirubin not greater than equal to 1.5 mg/dL not related to hemolysis or Gilberts disease, Aspartate transaminase (AST)/Alanine transaminase (ALT) 2 x upper limit of normal (ULN) 8. Serum creatinine not greater than equal to 1.5 mg/dL 9. Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of 130 mEq/L) 10. Women patients who are pregnant or lactating; male patients with female sexual partners who are unwilling to follow the strict contraception requirements described in this protocol ; patients who do not agree to use adequate contraceptive (including prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine device [IUD], double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) before entry & throughout the study, female patients with reproductive potential who do not have a negative serum or urine beta-human chorionic gonadotropin (beta HCG) pregnancy test at Screening 11. Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na treatment start 12. Uncontrolled hypertension (defined as a systolic pressure greater than or equal to 160 mm Hg and/or a diastolic pressure greater than or equal to 110 mm Hg) 13. New onset seizures (within 3 months prior to the first dose of ON 01910.Na) or poorly controlled seizures 14. Any concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy 15. Treatment with standard MDS therapies or investigational therapy within 4 weeks of starting ON 01910.Na 16. Psychiatric illness/social situations that would limit the patients ability to tolerate and/or comply with study requirements
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1.To explore and characterize pharmacokinetics following fasting oral administration of single and multiple doses of ON 01910.Na 2.To define the hematologic and non-hematologic toxicities of oral ON 01910.Na administered as single and multiple ascending dosesTimepoint: 1.Single dosing: Day1 of each cycle (weekly) till 6 weeks Multiple Dosing: Day 1 & Day 14 of each 3 week cycle From 8th week to 22nd week (5 cycles) 2.From Day of consent to 30 days after last dose of ON 01910.NA (Total duration 27 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| To determine, using the 2006 International Working Group (IWG) Criteria, the onset and duration of clinical response (Complete Remission, Partial Remission, and Hematologic Improvement), cytogenetic response and the bone marrow blast response in patients with refractory or progressive Intermediate-1, Intermediate-2, or High risk MDS following administration of ON 01910.Na by the methods used in this protocolTimepoint: At screening and at every 8 weeks of Multiple dosing.( total duration of 24 weeks) | — |
Countries
India
Contacts
Public ContactDr Manmohan Acharya
Outcome results
None listed