Previously untreated acute myeloid leukaemia in adult patients that are not eligible for intensive treatment, and adult patients with relapsed or refractory acute myeloid leukaemia that are not eligible for intensive treatment MedDRA version: 9.1 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia
Conditions
Interventions
Product Code: BI 811283
Pharmaceutical Form: Concentrate for solution for infusion
Current Sponsor code: BI 811283 BS
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concen
Sponsors
Boehringer Ingelheim Pharma GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • For the phase I part: male or female adult with previously untreated AML (except hydroxyurea, see protocol section 4.2.2) or relapsed/refractory AML. For the phase IIa part: 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Patient with APL (AML subtype M3 according to the French-American-British (FAB) classification) • Relapsed or treatment refractory AML (for phase II part only) • 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: 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.;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) | — |
Countries
Austria, Germany, Spain
Outcome results
None listed