Azacitidine With or Without Ceplene/Interleukin-2 in Patients With Higher Risk Myelodysplastic Syndromes

NCT ID: NCT01324960

Last Updated: 2014-03-20

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2014-12-31

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.

Conditions

Myelodysplastic Syndromes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ceplene® / IL2 + Azacitidine

Azacitidine 75 mg/m2 subcutaneously daily for 7 days every 4 weeks. Ceplene® / IL2: Patients will receive Ceplene (EpiCept Corporation, Tarrytown, NY) at 0.5 mg subcutaneous twice daily and human recombinant IL-2 (aldesleukin; Novartis) 16 400 U/kg subcutaneous twice daily during 15 days for up to 10 cycles, on days 8 to 21 of AZA cycles.

Group Type: EXPERIMENTAL

Ceplene®, IL-2, Azacitidine

Intervention Type: DRUG

Azacitidine: 75 mg/m2 subcutaneously daily for 7 days every 4 weeks. Ceplene® / IL2: Patients will receive Ceplene at 0.5 mg subcutaneous twice daily and human recombinant IL-2 at 16 400 U/kg subcutaneous twice daily during 15 days for up to 10 cycles, on days 8 to 21 of AZA cycles.

Azacitidine

Azacitidine 75 mg/m2 subcutaneously daily for 7 days every 4 weeks

Group Type: ACTIVE_COMPARATOR

Azacitidine

Intervention Type: DRUG

Azacitidine 75 mg/m2 subcutaneously daily for 7 days every 4 weeks

Interventions

Ceplene®, IL-2, Azacitidine

Azacitidine: 75 mg/m2 subcutaneously daily for 7 days every 4 weeks. Ceplene® / IL2: Patients will receive Ceplene at 0.5 mg subcutaneous twice daily and human recombinant IL-2 at 16 400 U/kg subcutaneous twice daily during 15 days for up to 10 cycles, on days 8 to 21 of AZA cycles.

Intervention Type: DRUG

Azacitidine

Azacitidine 75 mg/m2 subcutaneously daily for 7 days every 4 weeks

Intervention Type: DRUG

Other Intervention Names

Human recombinant IL-2 = Aldesleukin® (Novartis); Azacitidine = Vidaza® (Celgene); Azacitidine = Vidaza® (Celgene)

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

EpiCept Corporation

INDUSTRY

Sponsor Role: collaborator

Groupe Francophone des Myelodysplasies

OTHER

Sponsor Role: lead

Responsible Party

Groupe Francophone des Myelodysplasies

Principal Investigators

Céline BERTHON, MD

Role: PRINCIPAL_INVESTIGATOR

Groupe Francophone des Myelodisplasies

Bruno QUESNEL, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Groupe Francophone des Myelodisplasies

Pierre Fenaux, MD

Role: PRINCIPAL_INVESTIGATOR

Groupe francophone des Myelodisplasies

Locations

CHU d'Amiens

Amiens, , France

CHU Angers

Angers, , France

CH d'Avignon

Avignon, , France

Hôpital de la Côte Basque

Bayonne, , France

Hopital Avicenne

Bobigny, , France

CHU de Caen

Caen, , France

CHU de

Clermont-Ferrand, , France

Centre Hospitalier Sud-Francilien

Corbeil-Essonnes, , France

CHU Grenoble

Grenoble, , France

Hôpital Versailles

Le Chesnay, , France

Hôpital Saint Vincent

Lille, , France

CHRU Hurriez

Lille, , France

CHRU Limoges

Limoges, , France

Hôpital Edouard Heriot, dpt Hématologie Clinique

Lyon, , France

Hôpital Paoli-Calmettes

Marseille, , France

Hematology Dpt, Hopital de l'Hotel Dieu

Nantes, , France

CHU Archet

Nice, , France

Hopital Saint Louis

Paris, , France

Hôpital Saint Antoine

Paris, , France

Centre Hospitalier Joffre

Perpignan, , France

Hôpital Jean-Bernard

Poitiers, , France

CHRU de Reims

Reims, , France

Centre Henri Bequerel

Rouen, , France

Centre Hospitalier Universitaire de STRASBOURG

Strasbourg, , France

Hopital Purpan Service d'Hématologie Clinique

Toulouse, , France

Hopital Bretonneau

Tours, , France

CHU de Bicêtre

Le Kremlin-Bicêtre, Île-de-France Region, France

CHU Cochin

Paris, Île-de-France Region, France

Countries

France

Other Identifiers

GFM-Aza-ceplene

Identifier Type: -

Identifier Source: org_study_id