E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously untreated acute myeloid leukaemia in adult patients that are not eligible for intensive treatment |
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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 | 10000886 |
E.1.2 | Term | Acute myeloid leukemia |
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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 |
The trial will be performed in two parts, a phase I part and a phase IIa part. In the phase I part of the trial, two schedules of BI 811283 in combination with low-dose cytarabine (LD-Ara-C) will be investigated. In the phase I part, the dose of BI 811283 will be escalated to determine the maximum tolerated dose (MTD) of the two dosing schedules of BI 811283 in combination with LD-Ara-C. In the phase IIa part, the two combination schedules of BI 811283 at MTD with LD-Ara-C and one LD-Ara-C monotherapy schedule will be investigated to determine the efficacy (complete remission, CR; complete remission with incomplete blood count recovery, CRi) of the two combination schedules in comparison to LD-Ara-C monotherapy in previously untreated AML patients. |
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E.2.2 | Secondary objectives of the trial |
Further analysis of safety parameters including incidence and intensity of adverse events graded according to CTCAE (version 3.0) and incidence of dose limiting toxicity (DLT). Further analysis of efficacy parameters including partial remission (PR), event free survival (EFS), relapse free survival, remission duration, overall survival (OS), and supportive care requirements (blood products, antibiotic usage, hospitalisation). Pharmacodynamic monitoring: drug effect on leukaemia cells (e.g. polyploidy, histone H3 phosphorylation, morphologic changes) Pharmacokinetic analysis including:cytarabine after a single dose and at steady state when given alone and in combination with BI 811283, and pharmacokinetics of BI 811283 BS in the presence of cytarabine. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male or female adult with previously untreated AML (except hydroxyurea, see protocol section 4.2.2) • Confirmed diagnosis of AML according to the WHO definition (except for acute promyelocytic leukaemia, APL) • Patient is considered ineligible for intensive treatment • Patient is eligible for LD-Ara-C treatment • Life expectancy ≥ 3 months • Eastern co-operative oncology group (ECOG, R01-0787) performance score ≤ 2 at screening • Signed written informed consent consistent with international conference on harmonisation – good clinical practice (ICH-GCP) and local legislation |
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E.4 | Principal exclusion criteria |
• Patient with APL (AML subtype M3 according to the French-American-British (FAB) classification) • Relapsed or treatment refractory AML • Hypersensitivity to one of the trial drugs or the excipients • Other malignancy requiring treatment • Known central nervous system involvement • Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal • INR > 1.5 x ULN for subjects not on therapeutic vitamin K antagonists (phenprocoumon, warfarin) • Bilirubin greater than 1.5 mg/dl (> 26 μmol/l, SI unit equivalent) • Serum creatinine greater than 2.0 mg/dl • LVEF (Left ventricular ejection fraction) < 50% in echocardiography or clinical congestive heart failure New York Heart Association (NYHA) grade III - IV • Concomitant intercurrent illness, which would compromise the evaluation of efficacy or safety of the trial drug, e.g. active severe infection, unstable angina pectoris or cardiac arrhythmia • Psychiatric illness or social situation that would limit compliance with trial requirements • Concomitant therapy, which is considered relevant for the evaluation of the efficacy or safety of the trial drug (i.e. other chemo- or immunotherapy) • Contraindications for cytarabine treatment according to the summary of product characteristics (SPC) • Patients who are sexually active and unwilling to use a medically acceptable method of contraception during the trial (hormonal contraception, intrauterine device, condom with spermacide, etc.) • Pregnant or nursing female patients • Patient unable to comply with the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase I part: MTD of two schedules of BI 811283 in combination with LD-Ara-C
Phase IIa part: Response (complete remission, CR; complete remission with incomplete blood count recovery, CRi) |
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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 | Yes |
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 | 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 | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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) | Yes |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 | No |
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
|
The clinical trial will be considered completed as soon as the last patient has completed his / her last visit. In case the trial is ended by the sponsor when patients are still being treated with a clinical benefit from BI 811283, the patients will be offered to be treated in a follow-up trial which will be set up and allow patients to receive therapy with BI 811283. |
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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 | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |