Clinical trial NCT02985190: A Study of Azacitidine in Myelodysplastic Syndrome (MDS) Associated to Systemic Auto-immune and Inflammatory Disorders
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: MDS
Systemic Autoimmune Diseases
Keywords: Azacitidine
MDS
Systemic auto-immune and inflammatory disorders
Lead sponsor: Groupe Francophone des Myelodysplasies
Sponsor class: OTHER
Collaborators: name: Celgene
First posted: 2016-12-07
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Eligibility criteria: 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

Primary outcomes:
measure: Overall response rate of Myelodysplastic syndrome and systemic autoimmune and inflammatory diseases (SAID)
timeFrame: 6 months
Secondary outcomes:
measure: Number of participants with treament-related adverse events as assessed by CTCAE v4.0
timeFrame: up to 52 weeks
Other outcomes:
measure: Overall survival
timeFrame: 24 months
Locations:
city: Amiens cedex 01
country: France
facility: CHU Amiens
city: Angers cedex 9
country: France
facility: CHU d'Angers
city: Argenteuil
country: France
facility: Centre hospitalier Victor Dupouy
city: Avignon
country: France
facility: CH Henri Duffaut d'Avignon
city: Bayonne cedex
country: France
facility: Centre hospitalier de la Côte Basque
city: Belfort
country: France
facility: Hôpital Nord Franche-Comté
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Boulogne-sur-Mer
country: France
facility: Centre Hospitalier de Boulogne Sur Mer
city: Brest
country: France
facility: CHRU de Brest - Hôpital Morvan
city: Caen
country: France
facility: CHU Côte de Nacre
city: Cergy-Pontoise
country: France
facility: CH René Dubos
city: Chalon-sur-Saône
country: France
facility: Centre Hospitalier William Morey
city: Clermont-Ferrand
country: France
facility: CHU Estaing
city: Corbeil-Essonnes
country: France
facility: CHSF Gilles de Corbeil
city: Créteil
country: France
facility: CHU Henri Mondor
city: Dijon
country: France
facility: CHU François Mitterrand
city: Grenoble cedex 09
country: France
facility: CHU de Grenoble
city: La Rochelle
country: France
facility: Groupe Hospitalier de la Rochelle Ré Aunis
city: Le Mans cedex 09
country: France
facility: CH Le Mans
city: Le Mans
country: France
facility: Clinique Victor Hugo - Centre Jean Bernard
city: Lens
country: France
facility: Centre Hospitalier de Lens
city: Lille cedex
country: France
facility: Hôpital Claude Huriez
city: Lille
country: France
facility: Hôpital Saint Vincent de Paul
city: Limoges
country: France
facility: CHRU de Limoges - Hôpital Dupuytren
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Meaux cedex
country: France
facility: Centre Hospitalier de Meaux
city: Mont-de-Marsan
country: France
facility: CH de Mont de Marsan
city: Montpellier
country: France
facility: Clinique Beausoleil
city: Montpellier
country: France
facility: CHRU de Montpellier - Service de Médecine Interne
city: Montpellier
country: France
facility: CHU de Montpellier - Service d'hématologie Oncologie
city: Nantes cedex 1
country: France
facility: CHU Nantes - Hôtel Dieu
city: Nantes
country: France
facility: Centre Catherine de Sienne
city: Nice cedex 3
country: France
facility: Hôpital Archet 1
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Nîmes cedex 9
country: France
facility: CHU de Nîmes
city: Orléans
country: France
facility: CHR d'Orléans
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Hôpital Saint Antoine - Service de Médecine Interne
city: Paris
country: France
facility: Hôpital de La Pitié-Salpêtrière
city: Paris
country: France
facility: Hôpital Saint Antoine - Service d'Hématologie Clinique
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital Necker
city: Perpignan
country: France
facility: Centre Hospitalier Joffre
city: Pessac
country: France
facility: CHU de Haut-Lévèque
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon-Sud
city: Poitiers
country: France
facility: CHU de Poitiers
city: Pringy
country: France
facility: Centre Hospitalier Annecy Genevois
city: Reims
country: France
facility: CHU de Reims
city: Rennes
country: France
facility: Hôpital PONTCHAILLOU
city: Rochefort
country: France
facility: Centre Hospitalier de Rochefort
city: Roubaix
country: France
facility: Centrer Hospitalier de Roubaix
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint-Brieuc
country: France
facility: CH Yves Le Foll
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg
city: Toulouse
country: France
facility: IUCT Oncopole
city: Tours
country: France
facility: Hôpital Bretonneau
city: Troyes
country: France
facility: Centre Hospitalier de Troyes
city: Valence
country: France
facility: CH Valence
city: Vandoeuvre-les-Nancy
country: France
facility: CHU Brabois
Study officials:
affiliation: Saint Antoine Hospital
name: Arsene MEKINIAN, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Saint Antoine Hospital
name: Olivier FAIN, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Saint-Louis Hospital, Paris, France
name: Pierre FENAUX, PHD
role: STUDY_DIRECTOR
References: