Intensified Azacitidine in High Risk Myelodysplastic Syndrome (MDS)

NCT01305460 | Completed Phase 1

• 1 other identifier: GFM-AZA intensif
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 21

Brief Summary

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.

Conditions

Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• 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.

  After 4 courses treatment

  2 months

Secondary Outcomes (3)

• Safety/toxicity profile of azacitidine administered every 14 days (NCI-CTAE)

  1-24 months

• Responses (CR, PR, marrow CR, HI) according to IWG 2006 criteria and their duration.

  2-4 months

• Overall survival and progression (IPSS/AML) free survival.

  2 months and further

Study Arms (1)

Azacitidine intensified dose

EXPERIMENTAL

Drug: Azacitidine

Interventions

Azacitidine DRUG

Treatment will consist of azacitidine 75mg/m2/d for 5 days every 14 days for 4 cycles. * Patients achieving CR or PR will be then treated with 4 cycles of azacitidine 75mg/m2/d for 5 days every 21 days followed by cycles of azacitidine 75mg/m2/d for 7 days administered every 28 days (cycles 9 and beyond), to be continued until progression/relapse or toxicity arises. * Patients not obtaining CR or PR after the initial 4 cycles of azacitidine-14 will continue to receive azacitidine 75mg/m2/d for 5 days every 14 days for 4 additional cycles (cycles 5 to 8). If they achieve CR, PR or HI after 8 cycles, they will then be treated with azacitidine 75mg/m2/d for 5 days every 21 days (cycles 9 to 12) and subsequently cycles of azacitidine 75mg/m2/d for 7 days administered every 28 days (cycles 13 and beyond) until progression/relapse or toxicity arises. * Patients not obtaining CR, PR or HI after 8 cycles of azacitidine-14 will go "off-study".

Also known as: Vidaza

Azacitidine intensified dose

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• MDS defined according to WHO classification (also including RAEB-T according to FAB classification) (see appendix 1) with intermediate-2 or high risk IPSS (see appendix 1).
• Age ≥ 18 years and \<75 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 :
• Have a negative serum or urine pregnancy test within 2 weeks prior to beginning treatment on this study. Lactating patients are excluded.
• 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 :
• 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.
• Agree to learn about the procedures for preservation of sperm before starting treatment.
• Creatinine \< 1.5 N or estimated clearance of creatinine above 30 ml/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

You may not qualify if:

• Patients with a history of myeloproliferative syndrome or CMML.
• 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 fetus or a 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 bone marrow transplantation.
• Less than 3 months since prior autologous bone marrow or stem cell transplantation
• Active cancer or 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 of less than 3 months.

Sponsors & Collaborators

• Groupe Francophone des Myelodysplasies: lead

Study Sites (21)

CHU d'Amiens

Amiens, 80054, France

Location

Centre Hospitalier de La Cote Basque

Bayonne, 64100, France

Location

Hôpital Avicenne

Bobigny, 93009, France

Location

Centre henri Mondor

Créteil, 94010, France

Location

CHU Albert Michallon - Service d'Hématologie Clinique

Grenoble, 38043, France

Location

Centre Hospitalier du Mans

Le Mans, 72037, France

Location

Hôpital Huriez

Lille, 59037, France

Location

Hôpital Paoli Calmettes

Marseille, 13273, France

Location

Centre Hospitalier de Meaux

Meaux, 77100, France

Location

CHU Brabois

Nancy, 54511, France

Location

CHU de nantes

Nantes, 44093, France

Location

Hôpital l'Archet de Nice

Nice, 06202, France

Location

Hôpital Cochin

Paris, 75004, France

Location

Hôpital Saint Louis

Paris, 75010, France

Location

Hopital Saint Louis - AP-HP, Hematology Dpt

Paris, 75475, France

Location

CHU de Haut-Lévèque

Pessac, 33604, France

Location

CHU de Poitiers

Poitiers, 86021, France

Location

CHRU Annecy Hospital

Pringy, 74374, France

Location

Hôpital Pontchaillou

Rennes, 35033, France

Location

Hopital Purpan Service d'Hématologie Clinique

Toulouse, 31059, France

Location

CH de Valence

Valence, 26953, France

Location

Related Links

• Website of the Groupe Francophone des Myélodysplasies (GFM)

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Azacitidine

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

Study Officials

• Lionel Adès, MD

  Groupe Francophone des Myélodysplasies

  STUDY CHAIR

• Simone Boehrer, MD

  Groupe Francophone des Myélodysplasies

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2011
• First Posted: February 28, 2011
• Study Start: July 5, 2011
• Primary Completion: December 1, 2011
• Study Completion: November 16, 2015
• Last Updated: December 28, 2021

Record last verified: 2021-12

Locations

FR (21)