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

NCT01324960 | Withdrawn Phase 1 DMC

• 1 other identifier: GFM-Aza-ceplene
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 28

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

Keywords

IPSS; High risk; Azacitidine; Ceplene

Outcome Measures

Primary Outcomes (1)

• Time to progression according to IWG2006 criteria

  Progression will be assessed by monitoring the bone marrow, blood and hematologic supportive care according IWG 2006 criteria .

  Every 4 cycles (during average 2 years)

Secondary Outcomes (2)

• Types and numbers of adverse events occuring in all treated patients

  Every cycle, during the follow-up on average during 2 years

• Improvement of the quality and the duration of responses compared to maintenance with AZA alone

  While patient is on study, during follow up on average during 2 years

Study Arms (2)

Ceplene® / IL2 + Azacitidine

EXPERIMENTAL

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.

Drug: Ceplene®, IL-2, Azacitidine

Azacitidine

ACTIVE COMPARATOR

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

Drug: Azacitidine

Interventions

Ceplene®, IL-2, Azacitidine 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.

Also known as: Human recombinant IL-2 = Aldesleukin® (Novartis), Azacitidine = Vidaza® (Celgene)

Ceplene® / IL2 + Azacitidine

Azacitidine DRUG

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

Also known as: Azacitidine = Vidaza® (Celgene)

Azacitidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Groupe Francophone des Myelodysplasies: lead
• EpiCept Corporation: collaborator

Study Sites (28)

CHU d'Amiens

Amiens, 80054, France

Location

CHU Angers

Angers, 43033, France

Location

CH d'Avignon

Avignon, 84000, France

Location

Hôpital de la Côte Basque

Bayonne, 64100, France

Location

Hopital Avicenne

Bobigny, 93009, France

Location

CHU de Caen

Caen, 14033, France

Location

CHU de

Clermont-Ferrand, 63058, France

Location

Centre Hospitalier Sud-Francilien

Corbeil-Essonnes, 91106, France

Location

CHU Grenoble

Grenoble, 38043, France

Location

Hôpital Versailles

Le Chesnay, 78157, France

Location

Hôpital Saint Vincent

Lille, 59020, France

Location

CHRU Hurriez

Lille, 59057, France

Location

CHRU Limoges

Limoges, 87046, France

Location

Hôpital Edouard Heriot, dpt Hématologie Clinique

Lyon, 69437, France

Location

Hôpital Paoli-Calmettes

Marseille, 13273, France

Location

Hematology Dpt, Hopital de l'Hotel Dieu

Nantes, 44093, France

Location

CHU Archet

Nice, 06202, France

Location

Hopital Saint Louis

Paris, 75475, France

Location

Hôpital Saint Antoine

Paris, 75571, France

Location

Centre Hospitalier Joffre

Perpignan, 66046, France

Location

Hôpital Jean-Bernard

Poitiers, 86021, France

Location

CHRU de Reims

Reims, 51092, France

Location

Centre Henri Bequerel

Rouen, 76038, France

Location

Centre Hospitalier Universitaire de STRASBOURG

Strasbourg, 67098, France

Location

Hopital Purpan Service d'Hématologie Clinique

Toulouse, France

Location

Hopital Bretonneau

Tours, 37044, France

Location

CHU de Bicêtre

Le Kremlin-Bicêtre, Île-de-France Region, 94275, France

Location

CHU Cochin

Paris, Île-de-France Region, 75679, France

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Histamine; Interleukin-2; Azacitidine; lactitol

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Biogenic Monoamines; Biogenic Amines; Amines; Organic Chemicals; Ethylamines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Autacoids; Inflammation Mediators; Biological Factors; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Céline BERTHON, MD

  Groupe Francophone des Myelodisplasies

  PRINCIPAL INVESTIGATOR

• Bruno QUESNEL, MD, PhD

  Groupe Francophone des Myelodisplasies

  PRINCIPAL INVESTIGATOR

• Pierre Fenaux, MD

  Groupe francophone des Myelodisplasies

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 7, 2011
• First Posted: March 29, 2011
• Study Start: March 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: March 20, 2014

Record last verified: 2011-03

Locations

FR (28)