A Study of Azacitidine in Myelodysplastic Syndrome (MDS) Associated to Systemic Auto-immune and Inflammatory Disorders

October 3, 2022 updated by: Groupe Francophone des Myelodysplasies

A Phase II Study of Efficacy and Tolerance of Azacitidine (AZA) In MDS-associated Steroid Dependent/Refractory Systemic Auto-immune and Inflammatory Disorders (SAID)

This study is a phase II of effcicacy and tolerance of azacitidine in patients with myelodysplatic syndrome and steroid dependent or resistent systemic auto-immune and inflammatory disorders

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This trial will be a prospective French nationwide study analyzing the effect of treatment with azacitidine in patients with MDS-associated SAID with steroid dependence and/or resistance, and its correlation with possible changes in immunological parameters

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Amiens cedex 01, France, 80054
        • CHU Amiens
      • Angers cedex 9, France, 49933
        • CHU d'Angers
      • Argenteuil, France, 95107
        • Centre Hospitalier Victor Dupouy
      • Avignon, France, 84000
        • CH Henri Duffaut d'Avignon
      • Bayonne cedex, France, 64109
        • Centre Hospitalier de la Côte Basque
      • Belfort, France, 90015
        • Hopital Nord Franche-Comté
      • Bobigny, France, 93009
        • Hopital Avicenne
      • Boulogne-sur-Mer, France, 62321
        • Centre Hospitalier de Boulogne Sur Mer
      • Brest, France, 29609
        • CHRU de Brest - Hopital Morvan
      • Caen, France, 14033
        • CHU côte de Nacre
      • Cergy-Pontoise, France, 95303
        • CH René Dubos
      • Chalon-sur-Saône, France, 71100
        • Centre Hospitalier William Morey
      • Clermont-Ferrand, France, 63000
        • CHU Estaing
      • Corbeil-Essonnes, France, 91100
        • CHSF Gilles de Corbeil
      • Créteil, France, 94010
        • CHU Henri Mondor
      • Dijon, France, 21079
        • CHU François Mitterrand
      • Grenoble cedex 09, France, 38043
        • CHU de GRENOBLE
      • La Rochelle, France, 17000
        • Groupe Hospitalier de La Rochelle Ré Aunis
      • Le Mans, France, 72000
        • Clinique Victor Hugo - Centre Jean Bernard
      • Le Mans cedex 09, France, 72037
        • CH Le Mans
      • Lens, France, 62307
        • Centre Hospitalier de Lens
      • Lille, France, 59020
        • Hopital Saint Vincent de Paul
      • Lille cedex, France, 59037
        • Hôpital Claude Huriez
      • Limoges, France, 87042
        • CHRU de Limoges - Hôpital Dupuytren
      • Marseille, France, 13273
        • Institut Paoli Calmettes
      • Meaux cedex, France, 77104
        • Centre Hospitalier de Meaux
      • Mont-de-Marsan, France, 40000
        • CH de Mont de Marsan
      • Montpellier, France, 34000
        • Clinique Beausoleil
      • Montpellier, France, 34295
        • CHRU de Montpellier - Service de Médecine Interne
      • Montpellier, France, 34295
        • CHU de Montpellier - Service d'hématologie Oncologie
      • Nantes, France, 44277
        • Centre Catherine de Sienne
      • Nantes cedex 1, France, 44093
        • CHU Nantes - Hôtel Dieu
      • Nice, France, 06189
        • Centre Antoine Lacassagne
      • Nice cedex 3, France, 06202
        • Hôpital Archet 1
      • Nîmes cedex 9, France, 30029
        • CHU de Nîmes
      • Orléans, France, 45067
        • CHR d'Orléans
      • Paris, France, 75679
        • Hôpital Cochin
      • Paris, France, 75010
        • Hôpital Saint-Louis
      • Paris, France, 75743
        • Hopital Necker
      • Paris, France, 75013
        • Hôpital de la Pitié-Salpêtrière
      • Paris, France, 75012
        • Hopital Saint Antoine - service de médecine interne
      • Paris, France, 75571
        • Hôpital Saint Antoine - Service d'Hématologie Clinique
      • Perpignan, France, 66 046
        • Centre Hospitalier Joffre
      • Pessac, France, 33604
        • CHU de Haut-Lévèque
      • Pierre-Bénite, France, 69495
        • Centre Hospitalier Lyon-Sud
      • Poitiers, France, 86021
        • CHU De Poitiers
      • Pringy, France, 74374
        • Centre Hospitalier Annecy Genevois
      • Reims, France, 51092
        • CHU de Reims
      • Rennes, France, 35033
        • Hôpital Pontchaillou
      • Rochefort, France, 17301
        • Centre Hospitalier de Rochefort
      • Roubaix, France, 59056
        • Centrer Hospitalier de Roubaix
      • Rouen, France, 76038
        • Centre Henri Becquerel
      • Saint-Brieuc, France, 22000
        • CH Yves Le Foll
      • Strasbourg, France, 67091
        • Hopitaux Universitaires de Strasbourg
      • Toulouse, France, 31059
        • IUCT Oncopole
      • Tours, France, 37000
        • Hôpital Bretonneau
      • Troyes, France, 10003
        • Centre Hospitalier de Troyes
      • Valence, France, 26953
        • CH Valence
      • Vandoeuvre-les-Nancy, France, 54511
        • CHU Brabois

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Must understand and voluntarily sign the informed consent form
  • Age 18 years at the time of signing the informed consent form
  • Must be able to adhere to the study visit schedule and other protocol requirements

  • MDS or CMML or AML with 20-30% marrow blasts using 2008 WHO classification, with any of the following characteristics :

    1. IPSS intermediate 2 or high, including AML with 20 to 30% marrow blasts and CMML with WBC<13G/L and marrow blasts >10%,
    2. IPSS low or int 1 in need of treatment (transfusion dependent anemia resistant to ESAs and/or platelets below 30 G/l or below 50 G/l with bleeding or platelet transfusion requirement, and/or ANC < 0.5 G/l with infectious complications)
    3. Documented (by cytogenetic or molecular analysis) MDS /CMML not meeting those criteria, but with at least one significant cytopenia (Hb <10 g/dl, platelets <50G/l, ANC <1 G/l). In this situation, the underlying SAID should be severe and have resisted to a second line treatment (following steroids), if such treatment can be proposed for this particular SAID. Those cases should be discussed prior to inclusion with the trial sponsors complications)
  • SAID-associated with MDS defined according to usual international criteria for each SAID (ie ACR criteria for systemic lupus, Chapel Hill classification for systemic vasculitis, etc…)
  • Steroid dependence and/or resistance of SAID (steroid dependence being defined as the impossibility to decrease steroids during at least 2 months below 15 mg/day; steroid resistance as no response of SAID to at least 1 mg/kg/day of prednisone equivalent during one month)
  • Ineligibility for allogeneic stem cell transplantation during the following 12 months
  • Wash-out at least 6 months since a previous treatement with Lenalidomide
  • No previous use of hypomethylating agents
  • Life expectancy ≥ 6 months
  • Adequate liver function (serum transaminases ≤ 3N)
  • Adequate renal function (creatinine clearance with MDRD formula > 30 ml/min)

  • 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.

Exclusion Criteria:

  • IPSS low and intermediate-1 not meeting the criteria described above
  • Creatinine clearance with MDRD formula < 30 ml/min
  • Serum total bilirubin, or serum transaminases > 3.0 x upper limit of normal (ULN) (except for unconjugated hyperbilirubinemia due to Gilbert's disease or secondary to MDS)
  • Known hypersensitivity to the active substance or to any of the excipients of AZA
  • History of severe congestive heart failure, clinically unstable cardiac or pulmonary disease
  • Previous treatment with hypomethylating agents
  • Life-expectancy of less than six months because of another debilitating disease
  • Uncontrolled invasive fungal infection at time of registration or active serious infection not controlled by oral or intravenous antibiotics
  • Known positive for HIV or acute infectious hepatitis, type B or C
  • Any serious medical condition or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he/she participates in the study.
  • 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
  • Pregnant or lactating females
  • No affiliation to an insurance system

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Azacitidine 75mg/m²/day

Azacitidine 75mg/m²/j subcutaneously daily for 7 days every 4 weeks for a minimum of 6 cycles (unless overt disease progression, especially to Acute Myeloid Leukemia (AML) occure before 6 cycles) Azacitidine will be continued after 6 cycles

  • in patients with hematological response of myelodysplastic syndrome to azacitidine according to IWG2006 criteria by 6 cycles (Complete Response (CR), Partial Response (PR), marrow Complete Response (CRm), stable disease with Hematological Improvment (HI)), for another 6 cycles
  • in patients with complete or partial response of Systemic Auto-Immune Disorders (SAID) after 6 cycles of Azacitidine, even if Myelodysplastic Syndrome remains only stable per IWG2006 criteria
Drug: Azacitidine
Azacitidine at 75mg/m²/j for 7 days.
Other Names:
  • Vidaza

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate of Myelodysplastic syndrome and systemic autoimmune and inflammatory diseases (SAID)
Time Frame: 6 months
Overall response rate (including partial and complete response) of systemic autoimmune and inflammatory diseases associated with Myelodysplastic syndrome after 6 cycles of azacitidine
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with treament-related adverse events as assessed by CTCAE v4.0
Time Frame: up to 52 weeks
Number of participants with treament-related adverse events as assessed by CTCAE v4.0
up to 52 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 24 months
Overall survival
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Groupe Francophone des Myelodysplasies

Collaborators

Celgene

Investigators

  • Principal Investigator: Arsene MEKINIAN, MD, Saint Antoine Hospital
  • Principal Investigator: Olivier FAIN, PHD, Saint Antoine Hospital
  • Study Director: Pierre FENAUX, PHD, Saint-Louis Hospital, Paris, France

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 26, 2017

Primary Completion (ACTUAL)

September 2, 2021

Study Completion (ACTUAL)

August 30, 2022

Study Registration Dates

First Submitted

November 7, 2016

First Submitted That Met QC Criteria

December 2, 2016

First Posted (ESTIMATE)

December 7, 2016

Study Record Updates

Last Update Posted (ACTUAL)

October 4, 2022

Last Update Submitted That Met QC Criteria

October 3, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GFM-AZA-SAID
  • 2016-000918-30 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe