E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed Acute Myeloid Leukaemia (AML) expressing FLT-3 activating mutations. |
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MedDRA Classification |
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 |
The primary objective is to determine whether CEP 701 given in sequence with induction chemotherapy increases the proportion of patients with relapsed acute myeloid leukemia (AML) who achieve a second complete remission (CR) at the outcome assessment. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to determine the following: • the proportion of patients who achieve an outcome of CR with incomplete blood count recovery (CRi) • the proportion of patients who achieve an outcome of partial remission (PR) • the proportion of patients who maintain an outcome of CR up to day 113 • the proportion of patients who crossover to sequential CEP 701 treatment who achieve an outcome of CR at day 113 • remission duration (for patients who achieve a CR) • event-free survival • overall survival • safety and tolerability of CEP 701 administered in sequence with chemotherapy throughout the study • pharmacokinetics of CEP 701 at specified time points • CEP 701 inhibitory activity in plasma by means of a FLT 3 (fms-like tyrosine kinase 3) exvivo bioassay and cell assay at specified time points
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients are included in the study if all of the following criteria are met at the baseline visit: • cytological confirmation of AML • relapsed disease following first CR of a duration of 1 month (30 days) to 24 months (730 days). The time from first relapse to study entry (start of first course of induction chemotherapy) must be no longer than 30 days. • confirmation of FLT 3 activating mutation positive status after point of initial relapse • aged 18 years and older • written informed consent • ability to understand and comply with study restrictions • no comorbid conditions that would limit life expectancy to less than 3 months • Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1, or 2 • women must be neither pregnant nor lactating, and either of nonchildbearing potential or using adequate contraception with a negative pregnancy test at study entry
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E.4 | Principal exclusion criteria |
Patients are excluded from participating in this study if 1 or more of the following criteria are met: • bilirubin levels greater than 2 times upper limit of normal (ULN), alanine transaminase or aspartate transaminase levels greater than 3 times ULN • serum creatinine concentrations greater than 1.5 mg/dL • resting ejection fraction of left ventricle less than 45% (applies only to patients scheduled to receive mitoxantrone, etoposide, and cytarabine [MEC]) • untreated or progressive infection • any physical or psychiatric condition that may compromise participation in the study • known central nervous system involvement with AML • any previous treatment with a FLT 3 inhibitor • patient requires current treatment for the human immunodeficiency virus (HIV) with protease inhibitors • active gastrointestinal ulceration or bleeding • use of an investigational drug within 30 days of the baseline visit
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of patients who achieve an outcome of complete remission at the outcome assessment. The secondary variables are as follows: • the proportion of patients who achieve an outcome of CRi or PR • the proportion of patients who maintain an outcome of CR up to day 113 • the proportion of patients who achieve an outcome of CR at day 113 who crossover to sequential treatment with CEP 701 • remission duration (for patients who achieve a CR) • event-free survival for all patients • overall survival for all patients
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.8.1.2 | Open | No |
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) | 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.8.5 | 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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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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End of study is defined as the last visit of the last patient at the end of the follow up period. |
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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 | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |