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

Sponsor

Groupe Francophone des Myelodysplasies (Other)

Overall Status

Withdrawn

CT.gov ID

NCT01324960

Collaborator

EpiCept Corporation (Industry)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes	Drug: Ceplene®, IL-2, Azacitidine Drug: Azacitidine	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Mar 1, 2011

Anticipated Primary Completion Date :

Dec 1, 2014

Anticipated Study Completion Date :

Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	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. Other Names: Human recombinant IL-2 = Aldesleukin® (Novartis) Azacitidine = Vidaza® (Celgene)
Active Comparator: Azacitidine Azacitidine 75 mg/m2 subcutaneously daily for 7 days every 4 weeks	Drug: Azacitidine Azacitidine 75 mg/m2 subcutaneously daily for 7 days every 4 weeks Other Names: Azacitidine = Vidaza® (Celgene)

Arm

Intervention/Treatment

Experimental: 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.

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.

Other Names:

Human recombinant IL-2 = Aldesleukin® (Novartis)

Azacitidine = Vidaza® (Celgene)

Active Comparator: Azacitidine

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

Drug: Azacitidine

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

Other Names:

Azacitidine = Vidaza® (Celgene)

Outcome Measures

Primary Outcome Measures

Time to progression according to IWG2006 criteria [Every 4 cycles (during average 2 years)]
Progression will be assessed by monitoring the bone marrow, blood and hematologic supportive care according IWG 2006 criteria .

Secondary Outcome Measures

Types and numbers of adverse events occuring in all treated patients [Every cycle, during the follow-up on average during 2 years]
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.
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]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CHU de Bicêtre	Le Kremlin-Bicêtre	Ile de France	France	94275
2	CHU Cochin	Paris	Ile de France	France	75679
3	CHU d'Amiens	Amiens		France	80054
4	CHU Angers	Angers		France	43033
5	CH d'Avignon	Avignon		France	84000
6	Hôpital de la Côte Basque	Bayonne		France	64100
7	Hopital Avicenne	Bobigny		France	93009
8	CHU de Caen	Caen		France	14033
9	CHU de	Clermont Ferrand		France	63058
10	Centre Hospitalier Sud-Francilien	Corbeil-Essonnes		France	91106
11	CHU Grenoble	Grenoble		France	38043
12	Hôpital Versailles	Le Chesnay		France	78157
13	Hôpital Saint Vincent	Lille		France	59020
14	CHRU Hurriez	Lille		France	59057
15	CHRU Limoges	Limoges		France	87046
16	Hôpital Edouard Heriot, dpt Hématologie Clinique	Lyon		France	69437
17	Hôpital Paoli-Calmettes	Marseille		France	13273
18	Hematology Dpt, Hopital de l'Hotel Dieu	Nantes		France	44093
19	CHU Archet	Nice		France	06202
20	Hopital Saint Louis	Paris		France	75475
21	Hôpital Saint Antoine	Paris		France	75571
22	Centre Hospitalier Joffre	Perpignan		France	66046
23	Hôpital Jean-Bernard	Poitiers		France	86021
24	CHRU de Reims	Reims		France	51092
25	Centre Henri Bequerel	Rouen		France	76038
26	Centre Hospitalier Universitaire de STRASBOURG	Strasbourg		France	67098
27	Hopital Purpan Service d'Hématologie Clinique	Toulouse		France
28	Hopital Bretonneau	Tours		France	37044

Sponsors and Collaborators

Groupe Francophone des Myelodysplasies
EpiCept Corporation

Investigators

Principal Investigator: 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