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

Myelodysplastic Syndromes Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01324960
• Other study ID #: GFM-Aza-ceplene
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• First received: March 7, 2011
• Last updated: March 19, 2014
• Start date: March 2011
• Est. completion date: December 2014

Study information

• Verified date: March 2011
• Source: Groupe Francophone des Myelodysplasies
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• 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.
• Azacitidine
Azacitidine 75 mg/m2 subcutaneously daily for 7 days every 4 weeks

Locations

Country	Name	City	State
France	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	CHU de Bicêtre	Le Kremlin-Bicêtre	Ile de France
France	CHRU Hurriez	Lille
France	Hôpital Saint Vincent	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	CHU Cochin	Paris	Ile de France
France	Hôpital Saint Antoine	Paris
France	Hopital Saint Louis	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

Sponsors (2)

Lead Sponsor	Collaborator
Groupe Francophone des Myelodysplasies	EpiCept Corporation

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Yes
Secondary	Types and numbers of adverse events occuring in all treated patients	The safety profile will be determine by assessements of clinical symptoms, physical examinations, vital signs and clinical laboratory tests. The types and numbers of adverse events occuring in all treated patients will be tabulated.	Every cycle, during the follow-up on average during 2 years	Yes
Secondary	Improvement of the quality and the duration of responses compared to maintenance with AZA alone	The response will be assessed every 4 cycles according IWG 2006 criteria and it will be evaluated if there is an improvement of the level of response and the response duration	While patient is on study, during follow up on average during 2 years	Yes