Clinical trial NCT01324960: Azacitidine With or Without Ceplene/Interleukin-2 in Patients With Higher Risk Myelodysplastic Syndromes
Official title: A Phase I and Phase II Study of the Efficacy and Safety of Maintenance Treatment With Azacitidine With or Without Ceplene/Interleukin-2 in Patients With Higher Risk Myelodysplastic Syndromes Who Achieved Hematological Response to Azacitidine
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Myelodysplastic Syndromes
Keywords: IPSS
High risk
Azacitidine
Ceplene
Lead sponsor: Groupe Francophone des Myelodysplasies
Sponsor class: OTHER
Collaborators: name: EpiCept Corporation
First posted: 2011-03-29
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A phase I study of azacitidine with Ceplene/interleukin-2 will first evaluate the safety and tolerability of this regimen in patients with higher risk myelodysplastic syndromes (MDS) who achieved a hematological response after 6 cycles of azacitidine. After approval by an independent Data Safety Monitoring Board (DSMB), the phase I study will be followed by an open label randomized phase II study designed to characterize the efficacy, safety, and tolerability of the addition of Ceplene/interleukin-2 to azacytidine in patients with higher risk myelodysplastic syndrome (MDS) who achieved a hematological response after 6 cycles of azacitidine.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Must understand and voluntarily sign an informed consent form
* Must be able to adhere to the study visit schedule and other protocol requirements
* Documented diagnosis of MDS according to WHO classification, that meets IPSS criteria for intermediate-2 or high-risk disease
* Must have achieved a response (CR, PR, mCR or HI according to IWG 2006 criteria) after 6 cycles of Azacitidine.
* Patients must have ECOG performance status (PS) of 0 - 2.
* 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. Nursing patients are excluded.
* Creatinine clearance \>50 ml/min
* Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) \< 3.0 x upper limit of normal (ULN)
* Serum total bilirubin \< 1.5 mg/dL. (except for unconjugated hyperbilirubinemia due to Gilbert's disease or secondary to MDS).

Exclusion Criteria:

* Known positive status for human immunodeficiency virus (HIV) or hepatitis B or C
* Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Patients receiving any other standard or investigational cytotoxic treatment for their hematologic malignancy
* Any medical condition which in the opinion of the investigator places the patient at an unacceptably high risk for toxicities
* 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
* Class III or IV cardiac disease, hypotension or severe hypertension, vasomotor instability, serious or uncontrolled cardiac dysrhythmias (including ventricular arrhythmias) at any time, acute myocardial infarction within the past 12 months, active uncontrolled angina pectoris or symptomatic arteriosclerotic blood vessel disease
* History of seizures, central nervous disorders, stroke within the last 12 months, or psychiatric disability thought to be clinically significant in the opinion of the investigator
* Prior history of autoimmune disease (including but not limited to systemic lupus, inflammatory bowel disease, and psoriasis)
* Patients with active peptic or esophageal ulcer disease or with past peptic ulcer or esophageal disease with a history of bleeding
* Patients continuing systemic treatment with clonidine, steroids, and/or H2 receptor blocking agents Patients with a history of hypersensitivity to histamine or histamine products, severe allergies to food or contrast media requiring treatment within the last five years.

Primary outcomes:
measure: Time to progression according to IWG2006 criteria
timeFrame: Every 4 cycles (during average 2 years)
Secondary outcomes:
measure: Types and numbers of adverse events occuring in all treated patients
timeFrame: Every cycle, during the follow-up on average during 2 years
measure: Improvement of the quality and the duration of responses compared to maintenance with AZA alone
timeFrame: While patient is on study, during follow up on average during 2 years
Other outcomes:
Locations:
city: Le Kremlin-Bicêtre
country: France
facility: CHU de Bicêtre
state: Ile de France
city: Paris
country: France
facility: CHU Cochin
state: Ile de France
city: Amiens
country: France
facility: CHU d'Amiens
city: Angers
country: France
facility: CHU Angers
city: Avignon
country: France
facility: CH d'Avignon
city: Bayonne
country: France
facility: Hôpital de la Côte Basque
city: Bobigny
country: France
facility: Hopital Avicenne
city: Caen
country: France
facility: CHU de Caen
city: Clermont Ferrand
country: France
facility: CHU de
city: Corbeil-Essonnes
country: France
facility: Centre Hospitalier Sud-Francilien
city: Grenoble
country: France
facility: CHU Grenoble
city: Le Chesnay
country: France
facility: Hôpital Versailles
city: Lille
country: France
facility: Hôpital Saint Vincent
city: Lille
country: France
facility: CHRU Hurriez
city: Limoges
country: France
facility: CHRU Limoges
city: Lyon
country: France
facility: Hôpital Edouard Heriot, dpt Hématologie Clinique
city: Marseille
country: France
facility: Hôpital Paoli-Calmettes
city: Nantes
country: France
facility: Hematology Dpt, Hopital de l'Hotel Dieu
city: Nice
country: France
facility: CHU Archet
city: Paris
country: France
facility: Hopital Saint Louis
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Perpignan
country: France
facility: Centre Hospitalier Joffre
city: Poitiers
country: France
facility: Hôpital Jean-Bernard
city: Reims
country: France
facility: CHRU de Reims
city: Rouen
country: France
facility: Centre Henri Bequerel
city: Strasbourg
country: France
facility: Centre Hospitalier Universitaire de STRASBOURG
city: Toulouse
country: France
facility: Hopital Purpan Service d'Hématologie Clinique
city: Tours
country: France
facility: Hopital Bretonneau
Study officials:
affiliation: Groupe Francophone des Myelodisplasies
name: Céline BERTHON, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Groupe Francophone des Myelodisplasies
name: Bruno QUESNEL, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Groupe francophone des Myelodisplasies
name: Pierre Fenaux, MD
role: PRINCIPAL_INVESTIGATOR
References: