A phase I/II study of the efficacy and safety of an intensified schedule of Azacitidine (Vidaza®) in intermediate-2 and high risk MDS patients - GFM-Aza intensif

• Conditions: Myelodysplastic syndromes; MedDRA version: 12.1Level: LLTClassification code 10028533Term: Myelodysplastic syndrome

• Registration Number: EUCTR2010-020341-27-FR
• Lead Sponsor: Groupe Francophone des Myélodysplasies

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-05-18
• Last Update Posted: 12 October 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• MDS defined according to WHO classification (also including RAEB-T according to
FAB classification)(see appendix 1) with an intermediate-2 or high risk MDS IPSS
score (see appendix 1).
• Age = 18 years and <70 years.
• Must understand and voluntarily sign an informed consent form.
• Must be able to adhere to the study visit schedule and other protocol requirements.
• Patients must have ECOG performance status (PS) of 0 – 2, and no major
comorbidities preventing administration of an intensified regimen of azacitidine.
• Women of child-bearing potential (i.e., women who are pre-menopausal or not
surgically sterile) must:
o Have a negative serum or urine pregnancy test within 2 weeks prior to
beginning treatment on this study. Lactating patients are excluded.
o Agree to use, and to be able to comply with, effective contraception without
interruption, 4 weeks before starting study drug throughout the entire duration
study drug therapy (including doses interruptions) and for 3 months after the
end of the study drug therapy.
• Male patients must :
o Agree the need for the use of a condom if engaged in sexual activity with a
woman of childbearing potential during the entire period of treatment, even if
disruption of treatment and during 3 months after end of treatment.
o Agree to learn about the procedures for preservation of sperm before starting
treatment.
• Creatinine <1.5 N or estimated clearance of creatinine below 30ml/min.
• Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase
(SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase
(SGPT) > 3.0 x upper limit of normal (ULN).
• Serum total bilirubin > 1.5 mg/dL. (except for unconjugated hyperbilirubinemia due to
Gilbert’s disease or secondary to MDS-related dyserythropoiesis).
• Health insurance.
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

Known positive status for human immunodeficiency virus (HIV) or hepatitis B or C
• Pregnant and lactating patients are excluded because the effects of azacitidine on a
foetus or breast-fed child are unknown
• Uncontrolled intercurrent illness including, but not limited to uncontrolled infection,
symptomatic congestive heart failure (NYHA > II), cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with study requirements.
• Patients receiving any other standard or investigational cytotoxic treatment for their
hematologic malignancy in the last 8 weeks.
• Any medical condition which in the opinion of the investigator places the patient at an
unacceptably high risk for toxicities of an intensified regimen of azacitidine.
• Less than 6 months since prior allogeneic stem cell transplantation.
• Less than 3 months since prior autologous stem cell transplantation.
• Prior history of malignancy other than MDS (except basal cell or squamous cell
carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been free
of disease for = 3 years.
• Prior treatment with azacitidine.
• Known allergy/intolerance to azacitidine or mannitol.
• ECOG > 2.
• Life expectancy less than 3 months.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Response rate (including CR and PR) according to IWG 2006 criteria for MDS after 4 and 8 cycles 75mg/m2/d azacitidine administered every 2 weeks.;Secondary Objective: - Safety/toxicity profil of azacitidine administered every 14 days (NCI-CTAE)<br>- Responses (CR, PR, marrow CR, HI) according to IWG 2006 criteria and their duration<br>- Overall survival and progression (IPSS/AML) free survival<br>;Primary end point(s): Primary endpoint of the trial will be to assess the response rate according to IWG 2006 criteria for MDS<br>