BI 811283 in Combination With Cytarabine in Previously Untreated AML Ineligible for Intensive Treatment

An Open Phase I/IIa Trial to Investigate the Maximum Tolerated Dose, Safety, Efficacy and Pharmacokinetics of BI 811283 in Combination With Cytarabine in Patients With Previously Untreated Acute Myeloid Leukaemia Ineligible for Intensive Treatment

Investigation of maximum tolerated dose, safety, efficacy and pharmcokinetics of BI 811283 in combination with cytarabine (LD-Ara-C) in previously untreated acute myeloid leukaemia (AML) patients

Inclusion criteria:

• Male or female adult with previously untreated acute myeloid leukaemia (AML)
• 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 low-dose cytarabine (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

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 (ULN).
• INR > 1.5 x ULN for subjects not on therapeutic vitamin K antagonists (phenprocoumon, warfarin).
• Bilirubin greater than 1.5 mg/dl.
• 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 or 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, see also section 4.2.2).
• 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 spermicide, etc.).
• Pregnant or nursing female patients.
• Patient unable to comply with the protocol.