A Study of Azacitidine in Myelodysplastic Syndrome (MDS) Associated to Systemic Auto-immune and Inflammatory Disorders
A Phase II Study of Efficacy and Tolerance of Azacitidine (AZA) In MDS-associated Steroid Dependent/Refractory Systemic Auto-immune and Inflammatory Disorders (SAID)
2 other identifiers
interventional
30
1 country
59
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jan 2017
Longer than P75 for phase_2
59 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 7, 2016
CompletedFirst Posted
Study publicly available on registry
December 7, 2016
CompletedStudy Start
First participant enrolled
January 26, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 2, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
August 30, 2022
CompletedOctober 4, 2022
October 1, 2022
4.6 years
November 7, 2016
October 3, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall response rate of Myelodysplastic syndrome and systemic autoimmune and inflammatory diseases (SAID)
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 Outcomes (1)
Number of participants with treament-related adverse events as assessed by CTCAE v4.0
up to 52 weeks
Other Outcomes (1)
Overall survival
24 months
Study Arms (1)
Azacitidine 75mg/m²/day
EXPERIMENTALAzacitidine 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
Interventions
Eligibility Criteria
You may qualify if:
- 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 :
- IPSS intermediate 2 or high, including AML with 20 to 30% marrow blasts and CMML with WBC\<13G/L and marrow blasts \>10%,
- 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)
- 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 :
- +5 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Groupe Francophone des Myelodysplasieslead
- Celgenecollaborator
Study Sites (59)
CHU Amiens
Amiens, 80054, France
CHU d'Angers
Angers, 49933, France
Centre hospitalier Victor Dupouy
Argenteuil, 95107, France
CH Henri Duffaut d'Avignon
Avignon, 84000, France
Centre hospitalier de la Côte Basque
Bayonne, 64109, France
Hôpital Nord Franche-Comté
Belfort, 90015, France
Hôpital Avicenne
Bobigny, 93009, France
Centre Hospitalier de Boulogne Sur Mer
Boulogne-sur-Mer, 62321, France
CHRU de Brest - Hôpital Morvan
Brest, 29609, France
CHU Côte de Nacre
Caen, 14033, France
CH René Dubos
Cergy-Pontoise, 95303, France
Centre Hospitalier William Morey
Chalon-sur-Saône, 71100, France
CHU Estaing
Clermont-Ferrand, 63000, France
CHSF Gilles de Corbeil
Corbeil-Essonnes, 91100, France
CHU Henri Mondor
Créteil, 94010, France
CHU François Mitterrand
Dijon, 21079, France
CHU de Grenoble
Grenoble, 38043, France
Groupe Hospitalier de la Rochelle Ré Aunis
La Rochelle, 17000, France
Clinique Victor Hugo - Centre Jean Bernard
Le Mans, 72000, France
CH Le Mans
Le Mans, 72037, France
Centre Hospitalier de Lens
Lens, 62307, France
Hôpital Saint Vincent de Paul
Lille, 59020, France
Hôpital Claude Huriez
Lille, 59037, France
CHRU de Limoges - Hôpital Dupuytren
Limoges, 87042, France
Institut Paoli Calmettes
Marseille, 13273, France
Centre Hospitalier de Meaux
Meaux, 77104, France
CH de Mont de Marsan
Mont-de-Marsan, 40000, France
Clinique Beausoleil
Montpellier, 34000, France
CHRU de Montpellier - Service de Médecine Interne
Montpellier, 34295, France
CHU de Montpellier - Service d'hématologie Oncologie
Montpellier, 34295, France
CHU Nantes - Hôtel Dieu
Nantes, 44093, France
Centre Catherine de Sienne
Nantes, 44277, France
Centre Antoine Lacassagne
Nice, 06189, France
Hôpital Archet 1
Nice, 06202, France
CHU de Nîmes
Nîmes, 30029, France
CHR d'Orléans
Orléans, 45067, France
Hôpital Saint-Louis
Paris, 75010, France
Hôpital Saint Antoine - Service de Médecine Interne
Paris, 75012, France
Hôpital de La Pitié-Salpêtrière
Paris, 75013, France
Hôpital Saint Antoine - Service d'Hématologie Clinique
Paris, 75571, France
Hôpital Cochin
Paris, 75679, France
Hôpital Necker
Paris, 75743, France
Centre Hospitalier Joffre
Perpignan, 66 046, France
CHU de Haut-Lévèque
Pessac, 33604, France
Centre Hospitalier Lyon-Sud
Pierre-Bénite, 69495, France
CHU de Poitiers
Poitiers, 86021, France
Centre Hospitalier Annecy Genevois
Pringy, 74374, France
CHU de Reims
Reims, 51092, France
Hôpital PONTCHAILLOU
Rennes, 35033, France
Centre Hospitalier de Rochefort
Rochefort, 17301, France
Centrer Hospitalier de Roubaix
Roubaix, 59056, France
Centre Henri Becquerel
Rouen, 76038, France
CH Yves Le Foll
Saint-Brieuc, 22000, France
Hôpitaux Universitaires de Strasbourg
Strasbourg, 67091, France
IUCT Oncopole
Toulouse, 31059, France
Hôpital Bretonneau
Tours, 37000, France
Centre Hospitalier de Troyes
Troyes, 10003, France
CH Valence
Valence, 26953, France
CHU Brabois
Vandœuvre-lès-Nancy, 54511, France
Related Publications (1)
Boy M, Bisio V, Zhao LP, Guidez F, Schell B, Lereclus E, Henry G, Villemonteix J, Rodrigues-Lima F, Gagne K, Retiere C, Larcher L, Kim R, Clappier E, Sebert M, Mekinian A, Fain O, Caignard A, Espeli M, Balabanian K, Toubert A, Fenaux P, Ades L, Dulphy N. Myelodysplastic Syndrome associated TET2 mutations affect NK cell function and genome methylation. Nat Commun. 2023 Feb 3;14(1):588. doi: 10.1038/s41467-023-36193-w.
PMID: 36737440DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- 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 Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 7, 2016
First Posted
December 7, 2016
Study Start
January 26, 2017
Primary Completion
September 2, 2021
Study Completion
August 30, 2022
Last Updated
October 4, 2022
Record last verified: 2022-10