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

Sponsor
Groupe Francophone des Myelodysplasies (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02985190
Collaborator
Celgene (Industry)
30
Enrollment
59
Locations
1
Arm
68.1
Anticipated Duration (Months)
0.5
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
30 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study of Efficacy and Tolerance of Azacitidine (AZA) In MDS-associated Steroid Dependent/Refractory Systemic Auto-immune and Inflammatory Disorders (SAID)
Actual Study Start Date :
Jan 26, 2017
Actual Primary Completion Date :
Sep 2, 2021
Anticipated Study Completion Date :
Oct 1, 2022

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Overall response rate of Myelodysplastic syndrome and systemic autoimmune and inflammatory diseases (SAID) [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

    Secondary Outcome Measures

    1. Number of participants with treament-related adverse events as assessed by CTCAE v4.0 [up to 52 weeks]

      Number of participants with treament-related adverse events as assessed by CTCAE v4.0

    Other Outcome Measures

    1. Overall survival [24 months]

      Overall survival

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 CHU Amiens Amiens cedex 01 France 80054
    2 CHU d'Angers Angers cedex 9 France 49933
    3 Centre hospitalier Victor Dupouy Argenteuil France 95107
    4 CH Henri Duffaut d'Avignon Avignon France 84000
    5 Centre hospitalier de la Côte Basque Bayonne cedex France 64109
    6 Hôpital Nord Franche-Comté Belfort France 90015
    7 Hôpital Avicenne Bobigny France 93009
    8 Centre Hospitalier de Boulogne Sur Mer Boulogne-sur-Mer France 62321
    9 CHRU de Brest - Hôpital Morvan Brest France 29609
    10 CHU Côte de Nacre Caen France 14033
    11 CH René Dubos Cergy-Pontoise France 95303
    12 Centre Hospitalier William Morey Chalon-sur-Saône France 71100
    13 CHU Estaing Clermont-Ferrand France 63000
    14 CHSF Gilles de Corbeil Corbeil-Essonnes France 91100
    15 CHU Henri Mondor Créteil France 94010
    16 CHU François Mitterrand Dijon France 21079
    17 CHU de Grenoble Grenoble cedex 09 France 38043
    18 Groupe Hospitalier de la Rochelle Ré Aunis La Rochelle France 17000
    19 CH Le Mans Le Mans cedex 09 France 72037
    20 Clinique Victor Hugo - Centre Jean Bernard Le Mans France 72000
    21 Centre Hospitalier de Lens Lens France 62307
    22 Hôpital Claude Huriez Lille cedex France 59037
    23 Hôpital Saint Vincent de Paul Lille France 59020
    24 CHRU de Limoges - Hôpital Dupuytren Limoges France 87042
    25 Institut Paoli Calmettes Marseille France 13273
    26 Centre Hospitalier de Meaux Meaux cedex France 77104
    27 CH de Mont de Marsan Mont-de-Marsan France 40000
    28 Clinique Beausoleil Montpellier France 34000
    29 CHRU de Montpellier - Service de Médecine Interne Montpellier France 34295
    30 CHU de Montpellier - Service d'hématologie Oncologie Montpellier France 34295
    31 CHU Nantes - Hôtel Dieu Nantes cedex 1 France 44093
    32 Centre Catherine de Sienne Nantes France 44277
    33 Hôpital Archet 1 Nice cedex 3 France 06202
    34 Centre Antoine Lacassagne Nice France 06189
    35 CHU de Nîmes Nîmes cedex 9 France 30029
    36 CHR d'Orléans Orléans France 45067
    37 Hôpital Saint-Louis Paris France 75010
    38 Hôpital Saint Antoine - Service de Médecine Interne Paris France 75012
    39 Hôpital de La Pitié-Salpêtrière Paris France 75013
    40 Hôpital Saint Antoine - Service d'Hématologie Clinique Paris France 75571
    41 Hôpital Cochin Paris France 75679
    42 Hôpital Necker Paris France 75743
    43 Centre Hospitalier Joffre Perpignan France 66 046
    44 CHU de Haut-Lévèque Pessac France 33604
    45 Centre Hospitalier Lyon-Sud Pierre-Bénite France 69495
    46 CHU de Poitiers Poitiers France 86021
    47 Centre Hospitalier Annecy Genevois Pringy France 74374
    48 CHU de Reims Reims France 51092
    49 Hôpital PONTCHAILLOU Rennes France 35033
    50 Centre Hospitalier de Rochefort Rochefort France 17301
    51 Centrer Hospitalier de Roubaix Roubaix France 59056
    52 Centre Henri Becquerel Rouen France 76038
    53 CH Yves Le Foll Saint-Brieuc France 22000
    54 Hôpitaux Universitaires de Strasbourg Strasbourg France 67091
    55 IUCT Oncopole Toulouse France 31059
    56 Hôpital Bretonneau Tours France 37000
    57 Centre Hospitalier de Troyes Troyes France 10003
    58 CH Valence Valence France 26953
    59 CHU Brabois Vandoeuvre-les-Nancy France 54511

    Sponsors and Collaborators

    • Groupe Francophone des Myelodysplasies
    • 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 Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Groupe Francophone des Myelodysplasies
    ClinicalTrials.gov Identifier:
    NCT02985190
    Other Study ID Numbers:
    • GFM-AZA-SAID
    • 2016-000918-30
    First Posted:
    Dec 7, 2016
    Last Update Posted:
    Oct 12, 2021
    Last Verified:
    Oct 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Groupe Francophone des Myelodysplasies
    Azacitidine
    MDS
    Systemic auto-immune and inflammatory disorders
    Additional relevant MeSH terms:
    Autoimmune Diseases
    Azacitidine

    Study Results

    No Results Posted as of Oct 12, 2021