Intermediate II and high risk Myelodysplastic syndrome MDS MedDRA version: 8.1 Level: PT Classification code 10028533 Term: Myelodysplastic syndrome
Conditions
Interventions
Trade Name: DEPAKIN*40CPR GASTROR 200MG
Pharmaceutical Form: Gastro-resistant capsule, soft
INN or Proposed INN: Valproic acid
CAS Number: 1069-66-5
Concentration unit: mg milligram(s)
Concentration t
Sponsors
G.I.M.E.M.A. GRUPPO ITALIANO MALATTIE EMATOLOGICHE DELL ADULTO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Have a diagnosis of refractory anemia with excess blasts RAEB or refractory anemia with excess blasts in transformation RAEB-t according to the French-American-British classification system for MDS with an International Prognostic Scoring System score of INT-2 or High Appendix C or diagnosis of Myelodysplastic CMMoL per a modified FAB criteria Appendix B and a relatively high risk of AML transformation,; Age 8805;18 years; life expectancy 8805;3 months; Be unlikely to proceed to bone marrow or stem cell transplantation therapy following remission; Signed written informed consent according to IGH/EU/GCP and national local laws; Eastern Cooperative Oncology Group Performance Status Grade of 0-2 Appendix D ; Serum bilirubin levels 8804;1.5 x the upper limit of the normal ULN range for the laboratory; higher levels are acceptable if these can be attributed to active hemolysis as indicated by positive direct Coombs testing, decreased haptoglobin level, elevated indirect bilirubin and/or lactate dehydrogenase , or ineffective erythropoiesis as indicated by bone marrow findings ; Serum glutamic-oxaloacetic transaminase aspartate aminotransferase or serum glutamic-pyruvic transaminase alanine aminotransferase levels 8804;2 x ULN; Women of childbearing potential may participate, providing they meet the following conditions - Must not start a pregnancy throughout the study and for 6 months following the date of the last dose of study medications; - Must have a negative serum pregnancy test obtained within 48 hours prior to Day 1. Males with female partner of childbearing potential must avoid fathering throughout the study and for 6 months following the date of the last dose of study medication. 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: -acute myeloid leukaemia i.e. bone marrow blasts 30 ; -concurrent malignancy diagnosed in the past 12 months with the exception of skin basalioma ; -severe renal impairment creatinine clearance 30 ml/min ; -pregnant or lactating, or are potentially fertile both males and females and have not agreed to avoid pregnancy during the trial period; -they have liver disease characterized by AST and ALT level 2X ULN and total bilirubin 1.5X ULN unless due to active hemolysis or ineffective erythropoiesis; -HIV infection; -active, uncontrolled HCV or HBV infections or liver cirrhosis; -clinically relevant neurological diseases; -psychiatric illness that would prevent granting of informed consent; -hypersensitivity known or suspected to Azacytidine or Mannitol -prior Treatments Prior investigational drugs within 30 days Radiation therapy, chemotherapy, or cytotoxic therapy for non- MDS conditions within the previous 6 months Growth factors EPO, G-CSF or GM-CSF during the previous 21 days Androgenic hormones during the previous 14 days Prior transplantation or cytotoxic therapy, including azacitidine and chemotherapy, administered to treat MDS.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the trial is to assess the activity of the combined use of Valproic Acid VPA and with 5-Azacytidine 5-Aza C in the treatment of MDS. Activity will be evaluated as percentage of patients achieving complete or partial remission.;Secondary Objective: -Rate of patients achieving sustained haematological improvement -Number of blood and platelet transfusions -Number of infections requiring intravenous antibiotics/antimycotics -Number of days of hospitalization -Time to relapse after CR, PR or disease progression -Time to transformation to AML -Time to death from any cause. -Safety of the drug combination valproic acid/azacytidine -The prognostic and clinical significance of the molecular and cytogenetic features associated with response to therapy , time to progression, disease free survival and overall survival. -To perform biological studies including reactivation of tumor suppressor gene transcription through effect on DNA methylation, histone de-acetylase inhibitor HDAC inhibitor and to study the in vitro mechanisms of drug resistance and drug sensitivity. -In non responding patients this protocol would like to explore the safety, feasibility and activity of adding ATRA to the mentioned association.;Primary end point(s): The primary objective of the trial is to assess the efficacy of the combined use of Valproic Acid VPA and with 5-Azacytidine 5-Aza C in the treatment of MDS. Efficacy will be evaluated as percentage of patients achieving complete or partial remission | — |
Countries
Italy
Outcome results
None listed