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 | 7.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000880 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the overall response (OR) rate of older patients with untreated AML, for whom intensive chemotherapy is not considered suitable, when given clofarabine at the study dose schedule. 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. |
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E.2.2 | Secondary objectives of the trial |
1. To document the rate of CR(s) in the study population. 2. To document the rate of CRi(s) in the study population. 3. To document the rate of PR(s) in the study population. 4. To document time to event parameters including duration of remission and overall survival (OS) and time to remission. 5. To document the safety profile and tolerability of clofarabine for this population and dosing regimen. 6. To determine the pharmacokinetic profile and intracellular triphosphate levels of clofarabine in the study population.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Patients must have untreated AML as defined by the WHO classification (Appendix I) 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 (i.e., latex condom, diaphragm, cervical cap, etc) 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.
Inclusion Laboratory Values Parameter Required Value International Standard (IS units) Serum Bilirubin < 1.5 x ULN AST and ALT < 2 x ULN Creatinine < 1.7g/dL Prothrombin Time < 1.5 x control ULN = Institutional Upper Limit of Normal.
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E.4 | Principal exclusion criteria |
Patients who meet any of the following criteria will be excluded from study admission: 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
The Primary Efficacy Endpoint is: The overall response (OR) rate will be determined by assessment of morphology and blast count from bone marrow aspirates and peripheral blood performed prior to first dose and end of treatment. The OR rate will be defined as the sum of the number of patients in the study population with a CR, CRi or PR divided by the number of patients in the study population.
Secondary Efficacy Endpoints are: ·The CR rate will be determined by dividing the number of patients in the study population with a CR by the total number of patients in the study population. ·The CRi rate will be determined by dividing the number of patients in the study population with a CRi by the total number of patients in the study population. ·The PR rate will be determined by dividing the number of patients in the study population with a PR by the total number of patients in the study population. ·Overall survival (OS) will be calculated from the date of first dose of clofarabine to the date of death. ·Duration of remission will be calculated from the date of the first BM aspirate or blood sample which is documented to show remission to the date of the first BM aspirate or haematological analysis sample documented to show disease relapse or death due to any cause, whichever occurs first. ·Time to remission will be calculated from the date of first dose to date of first BM aspirate or blood sample which is documented to show remission. ·In patients who consent pharmacokinetic parameters and intracellular clofarabine triphosphate levels will be evaluated by standard assay methods.
Safety endpoints are: -Safety and tolerability will be evaluated by the incidence, severity (as assessed by the revised NCI CTCAE, version 3.0 (published 16 April 2003) duration, seriousness, and relationship of adverse events to the study drug occurring from the time the patient is consented until 30 days after the last study dose. All = grade 3 drug-related toxicities will be considered unacceptable toxicity with the following exceptions: nausea and vomiting (if manageable with supportive care measures), alopecia, drug-related fever, lymphopenia, and transient elevations in liver function tests. -Haematology (full blood count with differentials), Serum chemistry (for liver and renal function tests, including: urea, phosphorus, magnesium, lactate dehydrogenase (LDH), creatinine, uric acid, total protein, albumin, calcium, glucose, total bilirubin, alkaline phosphatase (ALP), AST, ALT, electrolytes (chloride, sodium, potassium, and bicarbonate), BUN and bone marrow aspirations -Prothrombin Time -Electrocardiogram (ECG). -Echocardiogram (ECHO) or Multiple-Gated Acquisition (MUGA) scan if clinically indicated. -Chest radiograph, or other imaging studies -A complete physical examination and medical history including previous and concurrent baseline conditions (using NCI CTC). -Measurements of height (cm) and weight (kg). -Karnofsky Performance Status evaluation. -Vital signs (blood pressure, pulse rate, respiratory rate, and temperature) -Concurrent medication
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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) | 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
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E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
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 | Information not present in EudraCT |
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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The end of the trial is the last patient visit |
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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 | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |