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PhII 5-Azacytidine Plus Valproic Acid and Eventually Atra in Intermediate II and High Risk MDS

This study is ongoing, but not recruiting participants.

Sponsored by: Gruppo Italiano Malattie EMatologiche dell'Adulto
Information provided by: Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier: NCT00439673
  Purpose

The primary objective of the trial is to assess the activity of the combined use of Valproic Acid (VPA)in combination with 5-Azacytidine (5-Aza C) in the treatment of MDS.

Activity will be evaluated as percentage of patients achieving complete or partial remission.


Condition Intervention Phase
Myelodysplastic Syndromes
Drug: 5-Azacytidine
Drug: Valproic Acid
Drug: ATRA
Phase II

ChemIDplus related topics:   Azacitidine    Divalproex sodium    Valproate Sodium    Valproic acid   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment
Official Title:   A Open Label, Phase II, Non Randomized, Clinical Trial of Chemotherapy Treatment With 5-Azacytidine Plus Valproic Acid and Eventually Atra for Patients Diagnosed With Intermediate II and High Risk Myelodysplastic Syndrome (MDS). EudraCT Number 2005-004811-31. GIMEMA Protocol MDS0205

Further study details as provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:

Primary Outcome Measures:
  • The primary objective of the trial is to assess the efficacy of the combined use of Valproic Acid (VPA) in combination with 5-Azacytidine (5-Aza C) in the treatment of MDS.
  • Efficacy will be evaluated as percentage of patients achieving complete or partial remission.

Secondary Outcome Measures:
  • 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
  • To assess 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 sensit
  • In non responding patients this protocol would like to explore the safety, feasibility and efficacy of adding ATRA to the mentioned association

Estimated Enrollment:   56
Study Start Date:   August 2006

Show detailed description  Show Detailed Description

  Eligibility
Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 or diagnosis of Myelodysplastic CMMoL per a modified FAB criteria and a relatively high risk of AML transformation;

    • Age ≥18 years;
    • life expectancy ≥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 ≤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 ≤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.

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.
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00439673

Locations
Italy
USL 8 di Arezzo    
      Arezzo, Italy
Azienda Ospedaliera S. G. Moscati    
      Avellino, Italy
Università degli studi di Bari    
      Bari, Italy
Università degli studi di Roma La Cattolica    
      Roma, Italy
Ospedale Reg. A di Summa    
      Brindisi, Italy
Ospedale A. Businco    
      Cagliari, Italy
Istituto ematologia e oncologia medica L.A. Seragnoli    
      Bologna, Italy

Sponsors and Collaborators
Gruppo Italiano Malattie EMatologiche dell'Adulto

Investigators
Principal Investigator:     Giuseppe LEONE, MD, PHD     Università degli studi di Roma La Cattolica    
  More Information


Study ID Numbers:   MDS0205
First Received:   February 23, 2007
Last Updated:   August 28, 2007
ClinicalTrials.gov Identifier:   NCT00439673
Health Authority:   Italy: The Italian Medicines Agency

Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
MDS  
5-Azacytidine  
valproic acid  
atra
intermediate or high risk
Age ≥18 yearsAge

Study placed in the following topic categories:
Myelodysplastic syndromes
Preleukemia
Precancerous Conditions
Hematologic Diseases
Myelodysplasia
Myelodysplastic Syndromes
Azacitidine
Bone Marrow Diseases
Valproic Acid

Additional relevant MeSH terms:
Antimetabolites
Neurotransmitter Agents
Disease
Antimetabolites, Antineoplastic
Tranquilizing Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Psychotropic Drugs
Central Nervous System Depressants
Enzyme Inhibitors
Antimanic Agents
Pharmacologic Actions
Neoplasms
Pathologic Processes
Syndrome
Therapeutic Uses
GABA Agents
Central Nervous System Agents
Anticonvulsants

ClinicalTrials.gov processed this record on October 10, 2008




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