E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Myelodysplastic syndromes |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028533 |
E.1.2 | Term | Myelodysplastic syndrome |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
For the Phase I study: To evaluate the safety and tolerability of vidaza and Ceplene/IL-2 used together.
For the phase II study: To determine if maintenance treatment with vidaza and Ceplene/IL-2 can improve, compared to maintenance treatment with vidaza alone, the time to progression in adult patients with higher risk MDS who achieved a response (CR, PR, mCR or HI according to IWG 2006 criteria) after 6 cycles of vidaza.
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E.2.2 | Secondary objectives of the trial |
Secondary objectives 1.Characterize the safety profile and the tolerability of AZA when used together with Ceplene/IL-2 2.Determine if maintenance with AZA and Ceplene/IL-2 can improve the quality of responses compared to maintenance with AZA alone Determine if maintenance with AZA and Ceplene/IL-2 can increase the duration of responses compared to maintenance with AZA alone.
Secondary endpoints: comparison of the 2 treatment arms for -safety -improvement of responses (from HI to PR or CR, according to IWG 2006 criteria) beyond 6 cycles -response duration -survival
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Age ≥ 18 years 2.Must understand and voluntarily sign an informed consent form 3.Must be able to adhere to the study visit schedule and other protocol requirements 4.Documented diagnosis of MDS according to WHO classification, that meets IPSS criteria for intermediate-2 or high-risk disease 5.Must have achieved a response (CR, PR, mCR or HI according to IWG 2006 criteria) after 6 cycles of Azacitidine. 6.Patients must have ECOG performance status (PS) of 0 – 2. 7.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 8. Creatinine clearance >50 ml/min 9.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) 10.Serum total bilirubin < 1.5 mg/dL. (except for unconjugated hyperbilirubinemia due to Gilbert’s disease or secondary to MDS).
11. Women of child-bearing potential Agree to use, and to be able to comply with, effective contraception without interruption, 4 weeks before starting study drug throughout the entire duration study drug therapy (including doses interruptions) and for 3 months after the end of the study drug therapy.
12. Male patients must : - Agree the need for the use of a condom if engaged in sexual activity with a woman of childbearing potential during the entire period of treatment, even if disruption of treatment and during 3 months after end of treatment. - Agree to learn about the procedures for preservation of sperm before starting treatment.
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E.4 | Principal exclusion criteria |
1.Known positive status for human immunodeficiency virus (HIV) or hepatitis B or C
2.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
3.Patients receiving any other standard or investigational cytotoxic treatment for their hematologic malignancy
4.Any medical condition which in the opinion of the investigator places the patient at an unacceptably high risk for toxicities
5.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
6.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
7.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
8.Prior history of autoimmune disease (including but not limited to systemic lupus, inflammatory bowel disease, and psoriasis)
9.Patients with active peptic or esophageal ulcer disease or with past peptic ulcer or esophageal disease with a history of bleeding
10.Patients continuing systemic treatment with clonidine, steroids, and/or H2 receptor blocking agents
11.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
12. Antecedent of allogeneic bone marrow transplantation |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is time to progression according to IWG 2006 criteria The appearance of progression will be assessed by monitoring the bone morrow, blood and hematologic supportive care |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
The Phase I will assess the feasibility and safety of Céplène/Interleukine-2 (IL-2) with vidaza |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Bras 1: Céplène/ IL-2 and vidaza / Bras 2: vidaza alone |
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E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 27 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |