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

NCT00439673 | Completed Phase 2 Results

• 1 other identifier: MDS0205
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Myelodysplastic Syndromes

Keywords

MDS; 5-Azacytidine; valproic acid; atra; intermediate or high risk; Age ≥18 yearsAge

Outcome Measures

Primary Outcomes (1)

• 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.

  Overall survival

  At 60 months

Secondary Outcomes (1)

• Time to Transformation to AML

  At 60 months

Interventions

5-Azacytidine DRUG

Valproic Acid DRUG

ATRA DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto: lead

Study Sites (7)

USL 8 di Arezzo

Arezzo, Italy

Location

Azienda Ospedaliera S. G. Moscati

Avellino, Italy

Location

Università degli studi di Bari

Bari, Italy

Location

Istituto ematologia e oncologia medica L.A. Seragnoli

Bologna, Italy

Location

Ospedale Reg. A di Summa

Brindisi, Italy

Location

Ospedale A. Businco

Cagliari, Italy

Location

Università degli studi di Roma La Cattolica

Roma, Italy

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Azacitidine; Valproic Acid

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Fatty Acids, Volatile; Fatty Acids; Lipids

Results Point of Contact

• Title: Alfonso Piciocchi
• Organization: GIMEMA

a.piciocchi@gimema.it

+39 06.70390521

Study Officials

• Giuseppe LEONE, MD, PHD

  Università degli studi di Roma La Cattolica

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2007
• First Posted: February 26, 2007
• Study Start: May 1, 2007
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: August 7, 2018
• Results First Posted: August 7, 2018

Record last verified: 2018-08

Locations

IT (7)