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

This study has been completed.
Sponsor:
Information provided by:
Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier:
NCT00439673
First received: February 23, 2007
Last updated: November 24, 2010
Last verified: November 2010
  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 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


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: May 2007
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Istituto ematologia e oncologia medica L.A. Seragnoli
Bologna, Italy
Ospedale Reg. A di Summa
Brindisi, Italy
Ospedale A. Businco
Cagliari, Italy
Università degli studi di Roma La Cattolica
Roma, 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

No publications provided

ClinicalTrials.gov Identifier: NCT00439673     History of Changes
Other Study ID Numbers: MDS0205
Study First Received: February 23, 2007
Last Updated: November 24, 2010
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

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Azacitidine
Valproic Acid
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Anticonvulsants
Central Nervous System Agents
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs

ClinicalTrials.gov processed this record on August 28, 2014