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

MDS Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02985190
• Other study ID #: GFM-AZA-SAID
• Secondary ID: 2016-000918-30
• Status: Completed
• Phase: Phase 2
• Start date: January 26, 2017
• Est. completion date: August 30, 2022

Study information

• Verified date: October 2022
• Source: Groupe Francophone des Myelodysplasies
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: August 30, 2022
• Est. primary completion date: September 2, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Autoimmune Diseases
• MDS
• Systemic Autoimmune Diseases

Intervention

Drug:
• Azacitidine
Azacitidine at 75mg/m²/j for 7 days.

Locations

Country	Name	City	State
France	CHU Amiens	Amiens cedex 01
France	CHU d'Angers	Angers cedex 9
France	Centre hospitalier Victor Dupouy	Argenteuil
France	CH Henri Duffaut d'Avignon	Avignon
France	Centre hospitalier de la Côte Basque	Bayonne cedex
France	Hôpital Nord Franche-Comté	Belfort
France	Hôpital Avicenne	Bobigny
France	Centre Hospitalier de Boulogne Sur Mer	Boulogne-sur-Mer
France	CHRU de Brest - Hôpital Morvan	Brest
France	CHU Côte de Nacre	Caen
France	CH René Dubos	Cergy-Pontoise
France	Centre Hospitalier William Morey	Chalon-sur-Saône
France	CHU Estaing	Clermont-Ferrand
France	CHSF Gilles de Corbeil	Corbeil-Essonnes
France	CHU Henri Mondor	Créteil
France	CHU François Mitterrand	Dijon
France	CHU de Grenoble	Grenoble cedex 09
France	Groupe Hospitalier de la Rochelle Ré Aunis	La Rochelle
France	Clinique Victor Hugo - Centre Jean Bernard	Le Mans
France	CH Le Mans	Le Mans cedex 09
France	Centre Hospitalier de Lens	Lens
France	Hôpital Saint Vincent de Paul	Lille
France	Hôpital Claude Huriez	Lille cedex
France	CHRU de Limoges - Hôpital Dupuytren	Limoges
France	Institut Paoli Calmettes	Marseille
France	Centre Hospitalier de Meaux	Meaux cedex
France	CH de Mont de Marsan	Mont-de-Marsan
France	CHRU de Montpellier - Service de Médecine Interne	Montpellier
France	CHU de Montpellier - Service d'hématologie Oncologie	Montpellier
France	Clinique Beausoleil	Montpellier
France	Centre Catherine de Sienne	Nantes
France	CHU Nantes - Hôtel Dieu	Nantes cedex 1
France	Centre Antoine Lacassagne	Nice
France	Hôpital Archet 1	Nice cedex 3
France	CHU de Nîmes	Nîmes cedex 9
France	CHR d'Orléans	Orléans
France	Hôpital Cochin	Paris
France	Hôpital de La Pitié-Salpêtrière	Paris
France	Hôpital Necker	Paris
France	Hôpital Saint Antoine - Service d'Hématologie Clinique	Paris
France	Hôpital Saint Antoine - Service de Médecine Interne	Paris
France	Hôpital Saint-Louis	Paris
France	Centre Hospitalier Joffre	Perpignan
France	CHU de Haut-Lévèque	Pessac
France	Centre Hospitalier Lyon-Sud	Pierre-Bénite
France	CHU de Poitiers	Poitiers
France	Centre Hospitalier Annecy Genevois	Pringy
France	CHU de Reims	Reims
France	Hôpital PONTCHAILLOU	Rennes
France	Centre Hospitalier de Rochefort	Rochefort
France	Centrer Hospitalier de Roubaix	Roubaix
France	Centre Henri Becquerel	Rouen
France	CH Yves Le Foll	Saint-Brieuc
France	Hôpitaux Universitaires de Strasbourg	Strasbourg
France	IUCT Oncopole	Toulouse
France	Hôpital Bretonneau	Tours
France	Centre Hospitalier de Troyes	Troyes
France	CH Valence	Valence
France	CHU Brabois	Vandoeuvre-les-Nancy

Sponsors (2)

Lead Sponsor	Collaborator
Groupe Francophone des Myelodysplasies	Celgene

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall survival	Overall survival	24 months
Primary	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	Number of participants with treament-related adverse events as assessed by CTCAE v4.0	Number of participants with treament-related adverse events as assessed by CTCAE v4.0	up to 52 weeks