E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIGH-RISK MYELODYSPLASTIC SYNDROME (MDS) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
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 |
The Main objective of the trial is to estimate the overall response rate (CR, PR, mCR and HI according to the IWG 2000 and 2006 criteria) in patients treated with erlotinib. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: •response duration •survival •correlation of prognostic parameters, response and survival, with the assessed biological parameters (NPM, p14 etc, for details see “biological studies”) •treatment-related toxicity
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria
1.Diagnosis of MDS according to the WHO classification, but also including RAEB in transformation as defined by the FAB classification (that is patients with up to 30% of blasts in the bone marrow); 2.Higher-risk MDS as defined by a IPSS score >1 (IPSS: Int-2 or High); 3.Life expectancy > 3 months; 4.Percentage of bone marrow blasts >10 and <30%; 5.Ineligible for or having failed intensive chemotherapy and ineligible for or having failed previous therapy with a hypomethylating agent; 6.Age ≥ 18 years; 7.Written informed consent; 8.Patient must understand and voluntarily sign consent form; 9.Patient must be able to adhere to the visit schedule as outlined in the study and follow protocol requirements; 10.ECOG performance status between 0-2 at the time of screening; 11.Females of childbearing potential (defined as a sexually mature woman who has not undergone a hysterectomy or who is not naturally postmenopausal for at least 24 consecutive months, that is who has had menses at any time during the preceeding 24 consecutive months) have to have a negative pregnancy test; 12.Adequate contraceptive methods should be carried out by all patients during therapy and for at least 2 weeks after completing therapy. 13.No existing contra-indication to treatment with erlotinib. 14.Health insurance.
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E.4 | Principal exclusion criteria |
Exclusion criteria 1.Serum creatinine ≥ 1.5 x the upper limit of normal, or creatinine clearance ≤60 mL/min; 2.Concomitant treatment with NSAIDS, warfarin, omeprazole, ranitidine or inducers (i.e. rifampicin, phenytoin; carbamazepin) or inhibitors (i.e. ketoconazole, ciprofloxacin, clarithromycine, voriconazole) of CYP3A4; 3.Inadequate liver function as defined by a serum bilirubine ≥1.5 x the upper limit of normal (except in the case of confirmed moderate unconjugated hyperbilirubinemia due to intramedullary hemolysis, as observed frequently in MDS), and/or ASAT/ALAT/GGT levels ≥2 x the upper limit of normal; 4.Known HIV-positivity; 5.Any serious medical condition or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he or she participates in the study; 6.Vitamine B12 or folate deficiency; 7.Pregnant or lactating females; 8.Use of cytotoxic chemotherapeutic agents or experimental agents (agents that are not commercially available) for the treatment of MDS within the 28 days preceeding study entry; 9.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 disease-free for ≥3 years; 10.Patients with a history of corneal disorders or another active ophthalmic disorder, active infections or other concomitant serious and uncontrolled medical conditions. 11.History of interstitial lung disease or any active pulmonary disease. Patients with a history of myeloproliferative syndrome or LMMC.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary end point:
The evaluation of the efficiency will be achieved by evaluating the response rate (CR, PR, mCR and HI) according to the IWG 2000 and 2006 criteria
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
First clinical study of Erlotinib in patients with higher risk myelodysplastic syndrome |
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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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
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 | No |
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 | 8 |
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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |