E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Myeloid Leukemia |
Leucemia Mieloide Acuta |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000880 |
E.1.2 | Term | Acute myeloid leukaemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
To determine the overall response (OR) rate with clofarabine in older patients with untreated AML, for whom intensive chemotherapy is not considered suitable. The OR rate is defined as the sum of the number of patients in the study population with complete remission (CR); complete remission with incomplete blood count recovery (CRi); and partial remission (PR) divided by the total number of patients in the study population. |
Determinare la percentuale di risposta complessiva (OR, overall response, definito quale la somma del numero di pazienti nella popolazione in studio con remissione completa (CR), remissione completa con recupero incompleto della conta delle cellule ematiche (CRi), e remissione parziale (PR), divisa per il numero totale di pazienti nella popolazione in studio. |
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E.2.2 | Secondary objectives of the trial |
To document in the study population: the rate of CR(s) CRi(s)and PR(s); time to event parameters including duration of complete remission and overall survival (OS) and time to complete remission for each patient up to 24 months after last dose of clofarabine; safety profile and tolerability of clofarabine for this population and dosing regimen; the pharmacokinetic profile and intracellular triphosphate levels of clofarabine in the study population. |
Documentare nella popolazione in studio: il tasso di CR,CRi e PR; il tempo all`evento di parametri comprendenti (a) durata di remissione,(b) sopravvivenza complessiva (OS,overall survival) e (c) tempo alla remissione per ogni paziente fino a 24 mesi dall`ultima dose di clofarabina; il profilo di sicurezza e tollerabilita` della clofarabina; il profilo di farmacocinetica e i tassi intracellulari di trifosfato della clofarabina. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
PHARMACOKINETIC/PHARMACODYNAMIC: Vers: Date: Title: Objectives:
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FARMACOCINETICA/FARMACODINAMICA: Vers: Data: Titolo: Obiettivi:
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E.3 | Principal inclusion criteria |
1. Patients must have untreated AML as defined by the WHO classification 2. Patients must provide written informed consent. 3. Male or Post-Menopausal female patients ≥ 65 years of age and unsuitable for intensive chemotherapy. 4. Male patients who are fertile agree to use an effective barrier method of birth control to avoid pregnancy. 5. Patients must be able to comply with study procedures and follow-up examinations. 6. Patients must have adequate organ function as indicated by the following laboratory values, obtained within 7 days prior to enrolment. Serum Bilirubin < 1.5 x ULN AST and ALT < 2 x ULN Creatinine < 1.5 x ULN Prothrombin Time < 1.5 x control ULN = Institutional Upper Limit of Normal. |
1. I pazienti devono presentare AML non trattata come definito dall aWHO classification 2. I pazienti devono fornire consenso informato scritto 3. Uomini o donne post menopausa ≥ 65 anni per cui la chemioterapia intensiva e` controindicata 4. Uomini fertili che accettano di utilizzare metodo barriera efficace per evitare gravidanze 5. Pazienti in grado di effettuare le procedure dello studio e gli esami di follow up. 6. Pazienti che possiedono una funzionalita` dei vari organi indicata dai seguenti valori di laboratorio ottenuti 7 giorni prima dell'arruolamento. Bilirubina serica < 1.5 x ULN AST e ALT < 2 x ULN Creatinina < 1.5 x ULN Tempo di Protrombina < 1.5 x controllo ULN = Range di normalita` superiore del centro |
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E.4 | Principal exclusion criteria |
1. Patients who have an active, uncontrolled systemic infection considered opportunistic, life threatening or clinically significant at the time of treatment. 2. Patients who have a psychiatric disorder(s) that would interfere with consent, study participation or follow-up. 3. Patients who are receiving other chemotherapy or corticosteroids (unless the latter is administered at a low dose for pre-medication purposes or for the treatment of chronic conditions - e.g., rheumatoid arthritis). 4. Patients who have received prior treatment for leukaemia. Patients who have received growth factor, cytokine support, leukopheresis or, hydroxyurea, will be allowed into the study but must discontinue treatment at least 24 hours prior to beginning treatment with clofarabine. 5. Patients who have any other severe concurrent disease (severe Coronary Artery Disease (CAD), significant neurological disorder, uncontrolled diabetes, etc), which, in the judgment of the investigator, would make the patient inappropriate for entry into this study. 6. Patients who have symptomatic Central Nervous System (CNS) involvement. 7. Patients who have previously received clofarabine. 8. Patients who are currently participating in other investigational drug studies or having received other investigational drugs within the previous 30 days. 9. Blast transformation of chronic myeloid leukaemia or acute promyelocytic leukaemia. |
1. Pazienti con infezione sistemica non controllata considerata opportunistica, che porta a pericolo di vita o clinicamente significativa al momento del trattamento. 2 Pazienti con disturbi psichiatrici che possono interferire con le procedure di consenso, partecipazione allo studio o follow up. 3. Pazienti che stanno ricevendo altri chemioterapici o corticosteroidi (a meno che quest'ultimi siano somministrati a bassa dose come pre.medicazione o trattamento di condizioni croniche come l'artite reumatoide). 4. Pazienti che hanno ricevuto un precedente trattamento per la leucemia. Pazienti che hanno ricevuto fattori di crescita, terapia di supporto con citochine, leucoferesi o idrossiurea sono arruolabili nello studio ma devono aver interrotto la terapia almeno 24 ore prima dell'inizio del trattamento con clofarabina. 5. Pazienti con alter patologie concomitanti gravi (Coronaropatia (CAD), disturbi neurologici significativi, diabete non controllato, etc), per i quali, secondo il parere dello sperimentatore, rendono l'inserimento del paziente nello studio non appropraito 6. Pazienti con coinvolgimento sintomatico del Sistema Nervoso Centrale (CNS) 7. Pazienti che hanno ricevuto precedentemente clofarabina 8. Pazienti che stanno partecipando in latri studi con farmaci sperimentali o che hanno ricevuto farmaci sperimentali nei 30 giorni precedenti.. 9. Trasformazione dei blasti della leucemia mieloide cronica o della leucemia promielocitica acuta. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Tumor response, toxicity |
Risposta tumorale, tossicita` |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
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 | No |
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) | 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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
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 | No |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |