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

NCT ID: NCT02985190

Last Updated: 2022-10-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-01-26

Study Completion Date

2022-08-30

Brief Summary

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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

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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

Conditions

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MDS Systemic Autoimmune Diseases

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Azacitidine

Intervention Type DRUG

Azacitidine at 75mg/m²/j for 7 days.

Interventions

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Azacitidine

Azacitidine at 75mg/m²/j for 7 days.

Intervention Type DRUG

Other Intervention Names

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Vidaza

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celgene

INDUSTRY

Sponsor Role collaborator

Groupe Francophone des Myelodysplasies

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Arsene MEKINIAN, MD

Role: PRINCIPAL_INVESTIGATOR

Saint Antoine Hospital

Olivier FAIN, PHD

Role: PRINCIPAL_INVESTIGATOR

Saint Antoine Hospital

Pierre FENAUX, PHD

Role: STUDY_DIRECTOR

Saint-Louis Hospital, Paris, France

Locations

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CHU Amiens

Amiens, , France

Site Status

CHU d'Angers

Angers, , France

Site Status

Centre hospitalier Victor Dupouy

Argenteuil, , France

Site Status

CH Henri Duffaut d'Avignon

Avignon, , France

Site Status

Centre hospitalier de la Côte Basque

Bayonne, , France

Site Status

Hôpital Nord Franche-Comté

Belfort, , France

Site Status

Hôpital Avicenne

Bobigny, , France

Site Status

Centre Hospitalier de Boulogne Sur Mer

Boulogne-sur-Mer, , France

Site Status

CHRU de Brest - Hôpital Morvan

Brest, , France

Site Status

CHU Côte de Nacre

Caen, , France

Site Status

CH René Dubos

Cergy-Pontoise, , France

Site Status

Centre Hospitalier William Morey

Chalon-sur-Saône, , France

Site Status

CHU Estaing

Clermont-Ferrand, , France

Site Status

CHSF Gilles de Corbeil

Corbeil-Essonnes, , France

Site Status

CHU Henri Mondor

Créteil, , France

Site Status

CHU François Mitterrand

Dijon, , France

Site Status

CHU de Grenoble

Grenoble, , France

Site Status

Groupe Hospitalier de la Rochelle Ré Aunis

La Rochelle, , France

Site Status

Clinique Victor Hugo - Centre Jean Bernard

Le Mans, , France

Site Status

CH Le Mans

Le Mans, , France

Site Status

Centre Hospitalier de Lens

Lens, , France

Site Status

Hôpital Saint Vincent de Paul

Lille, , France

Site Status

Hôpital Claude Huriez

Lille, , France

Site Status

CHRU de Limoges - Hôpital Dupuytren

Limoges, , France

Site Status

Institut Paoli Calmettes

Marseille, , France

Site Status

Centre Hospitalier de Meaux

Meaux, , France

Site Status

CH de Mont de Marsan

Mont-de-Marsan, , France

Site Status

Clinique Beausoleil

Montpellier, , France

Site Status

CHRU de Montpellier - Service de Médecine Interne

Montpellier, , France

Site Status

CHU de Montpellier - Service d'hématologie Oncologie

Montpellier, , France

Site Status

CHU Nantes - Hôtel Dieu

Nantes, , France

Site Status

Centre Catherine de Sienne

Nantes, , France

Site Status

Centre Antoine Lacassagne

Nice, , France

Site Status

Hôpital Archet 1

Nice, , France

Site Status

CHU de Nîmes

Nîmes, , France

Site Status

CHR d'Orléans

Orléans, , France

Site Status

Hôpital Saint-Louis

Paris, , France

Site Status

Hôpital Saint Antoine - Service de Médecine Interne

Paris, , France

Site Status

Hôpital de La Pitié-Salpêtrière

Paris, , France

Site Status

Hôpital Saint Antoine - Service d'Hématologie Clinique

Paris, , France

Site Status

Hôpital Cochin

Paris, , France

Site Status

Hôpital Necker

Paris, , France

Site Status

Centre Hospitalier Joffre

Perpignan, , France

Site Status

CHU de Haut-Lévèque

Pessac, , France

Site Status

Centre Hospitalier Lyon-Sud

Pierre-Bénite, , France

Site Status

CHU de Poitiers

Poitiers, , France

Site Status

Centre Hospitalier Annecy Genevois

Pringy, , France

Site Status

CHU de Reims

Reims, , France

Site Status

Hôpital PONTCHAILLOU

Rennes, , France

Site Status

Centre Hospitalier de Rochefort

Rochefort, , France

Site Status

Centrer Hospitalier de Roubaix

Roubaix, , France

Site Status

Centre Henri Becquerel

Rouen, , France

Site Status

CH Yves Le Foll

Saint-Brieuc, , France

Site Status

Hôpitaux Universitaires de Strasbourg

Strasbourg, , France

Site Status

IUCT Oncopole

Toulouse, , France

Site Status

Hôpital Bretonneau

Tours, , France

Site Status

Centre Hospitalier de Troyes

Troyes, , France

Site Status

CH Valence

Valence, , France

Site Status

CHU Brabois

Vandœuvre-lès-Nancy, , France

Site Status

Countries

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France

References

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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.

Reference Type DERIVED
PMID: 36737440 (View on PubMed)

Other Identifiers

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2016-000918-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GFM-AZA-SAID

Identifier Type: -

Identifier Source: org_study_id

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