E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009700 |
E.1.2 | Term | CML |
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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 |
The primary objective is to assess the efficacy of IPH1101 associated with low dose of IL-2 as add-on therapy to imatinib in CML patients with residual molecular disease after at least 2 years of imatinib monotherapy. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: - To determine the safety of IPH1101/ IL-2 low dose association in combination with imatinib - To assess the biological activity of the combination - To investigate the relationship between biological activity and efficacy of the combination. - To determine the duration of effect (complete molecular response) - To document the rate of progression free survival
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Signed informed consent prior to any protocol-specific procedures 2) BCR-ABL positive CML treated with first line imatinib as follow: At least 2 years of treatment with imatinib, At least 3 months since any imatinib dosage modification, 3) Complete cytogenetic response ((CCR) confirmed by recent cytogenetic analysis < 6 months) 4) Bcr-Abl/Abl ratio measured by qRT-PCR in blood (according to the european recommendations) between ≤ 1% and > 0,001% within 3 months prior to inclusion. 5) Dosage of imatinib at screening and pre-inclusion within the range 800ng/ml – 1800ng/ml 6) Aged over 18 years 7) Adequate bone marrow, hepatic and renal function as follows: - Lymphocytes > or = 900/µl - Platelets > or =100 x 10E9/l, - Total bilirubin < or = 2 x upper limit normal (ULN) - Transaminases (AST [SGOT]; ALT SGPT]) < ou = 3 x ULN - Serum creatinine < or = 2 x ULN 8) Normal thyroid function ( 0,15< TSH<5mU/l) 9) QTc interval duration < 430 ms for men, < 450 ms for women 10) At least 2 weeks since previous surgery 11) Male or female patient who accepts and is able to use recognised highly effective contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly, or surgically sterile) throughout the study.
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E.4 | Principal exclusion criteria |
1) Pregnant or lactating women 2) Concurrent treatment with any other anti-cancer therapy or any forbidden concomitant treatments: - Biphosphonates and immunosuppressive agents, - Systemic and chronic inhaled steroids, - Beta-blockers and calcium channel blockers 3) Participation in another clinical trial with any investigative drug within 30 days prior to study randomisation 4) Prior history of high dose chemotherapy followed by bone marrow or peripheral stem cell support or presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to study inclusion) 5) Any known hypersensitivity to one of the study treatments 6. Current active infection 7) Serious concurrent uncontrolled medical disorder such as diabetes, autoimmune disease, 8) Severe viral infection HIV, HCV, HBV (HBsAg) 9) Cardiovascular disease: - Stage III or IV congestive heart failure (CHF) as determined by the New York Heart Association (NYHA) classification system for heart failure. Note: patients with NYHA stage I or II CHF may be included provided they do not have arrythmia requiring treatment or fulfil any other exclusion criteria, - Myocardial infarction within the previous 6 months, or - Symptomatic cardiac arrhythmia requiring treatment, 10) History of another malignancy within the past 5 years, except basal cell carcinoma of the skin or carcinoma in situ of the cervix, 11) Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed with the patient before request for inclusionin the trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be the rate of patients achieving a complete molecular response (Bcr-Abl/Abl < 0.001%) within 24 weeks and confirmed on second determination 3 weeks later. The primary efficacy analysis will be performed on the population of evaluable patients. Patients evaluable for primary efficacy criteria will be defined as follows: Patients who receive at least one adequate cycle of IPH1101 associated with low dose of IL-2 and are evaluated for Bcr-Abl plasma level until at least 24 weeks.
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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 | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
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 |
It is a phase I like period, followed by a phase II |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 15 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |