Ground Truth
Inclusion Criteria:Male or female adult with relapsed/refractory AML ineligible for intensive treatment (phase I part only)Male or female adult with previously untreated AML ineligible for intensive treatment (phase IIa part only)Confirmed diagnosis of AML according to the WHO definition (except for acute promyelocytic leukaemia, APL)Patient is eligible for LD-Ara-C treatmentLife expectancy > 3 monthsEastern co-operative oncology group (ECOG, R01-0787) performance score >=2 at screeningSigned written informed consent consistent with international conference on harmonisation, good clinical practice (ICH-GCP) and local legislationExclusion Criteria:Previously untreated AML (phase I part only)Relapsed or treatment refractory AML (phase IIa part only)Patient with APL (AML subtype M3 according to the French-American-British (FAB) classification)Hypersensitivity to one of the trial drugs or the excipientsOther malignancy requiring treatmentSymptomatic central nervous system involvementClinically relevant QT prolongation (e.g.
long QT syndrome)Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (ULN), or AST or ALT greater than 5 times the ULN in case of known leukaemia liver involvementProthrombin time (PT) > 1.5 x ULN for subjects not on therapeutic vitamin K antagonists (phenprocoumon, warfarin)Bilirubin greater than 1.5 mg/dl (> 26 mcmol/L)Serum creatinine greater than 2.0 mg/dlConcomitant 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 arrhythmiaPsychiatric illness or social situation that would limit compliance with trial requirementsConcomitant therapy, which is considered relevant for the evaluation of the efficacy or safety of the trial drugContraindications for cytarabine treatment according to the SPCFemale patients of childbearing potential who are sexually active and unwilling to use a medically acceptable method of contraception during the trial, i.e.
combination of two forms of effective contraception (hormonal contraception, intrauterine device, condom with spermicide, etc.).Male patients with partners of childbearing potential who are unwilling to use condoms in combination with a second medically acceptable method of contraception during the trialPregnant or nursing female patientsPatient unable to comply with the protocol
Prediction
Amended Eligibility Criteria (version 3):
Inclusion Criteria:
- Male or female adult with relapsed/refractory AML ineligible for intensive treatment (phase I part only)
- Male or female adult with previously untreated AML ineligible for intensive treatment (phase IIa part only)
- Confirmed diagnosis of AML according to the WHO definition (except for acute promyelocytic leukaemia, APL)
- Patient is eligible for LD-Ara-C treatment
- Life expectancy ≥ 3 months
- Eastern Cooperative Oncology Group (ECOG) performance score ≥ 2 at screening
- Signed written informed consent consistent with international conference on harmonization, good clinical practice (ICH-GCP) and local legislation
- No hypersensitivity to one of the trial drugs or the excipients
- No other malignancy requiring treatment
- No symptomatic central nervous system involvement
- No clinically relevant QT prolongation (e.g., long QT syndrome, QTcF > 470 ms)
- Aspartate amino transferase (AST) or alanine amino transferase (ALT) ≤ 2.5 times the upper limit of normal (ULN), or AST or ALT ≤ 5 times the ULN in case of known leukaemia liver involvement
- Prothrombin time (PT) ≤ 1.5 x ULN for subjects not on therapeutic vitamin K antagonists (phenprocoumon, warfarin)
- Bilirubin ≤ 1.5 mg/dL (≤ 26 #mol/L)
- Serum creatinine ≤ 2.0 mg/dL
- No 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, or severe heart failure/cardiac insufficiency
- No psychiatric illness or social situation that would limit compliance with trial requirements
- No concomitant therapy, which is considered relevant for the evaluation of the efficacy or safety of the trial drug
- No contraindications for cytarabine treatment according to the SPC
- Female patients of childbearing potential who are sexually active and unwilling to use a medically acceptable method of contraception during the trial, i.e.
combination of two forms of effective contraception (hormonal contraception, intrauterine device, condom with spermicide, etc.)
- Male patients with partners of childbearing potential who are unwilling to use condoms in combination with a second medically acceptable method of contraception during the trial
- Not pregnant or nursing
- Patient able to comply with the protocol
Exclusion Criteria:
- Previously untreated AML (phase I part only)
- Relapsed or treatment refractory AML (phase IIa part only)
- Patient with APL (AML subtype M3 according to the French-American-British (FAB) classification)
- Hypersensitivity to one of the trial drugs or the excipients
- Other malignancy requiring treatment
- Symptomatic central nervous system involvement
- Clinically relevant QT prolongation (e.g., long QT syndrome, QTcF > 470 ms)
- Aspartate amino transferase (AST) or alanine amino transferase (ALT) > 2.5 times the upper limit of normal (ULN), or AST or ALT > 5 times the ULN in case of known leukaemia liver involvement
- Prothrombin time (PT) > 1.5 x ULN for subjects not on therapeutic vitamin K antagonists (phenprocoumon, warfarin)
- Bilirubin > 1.5 mg/dL (> 26 #mol/L)
- Serum creatinine > 2.0 mg/dL
- Concomitant intercurrent illness, which would compromise the evaluation of efficacy or safety of the trial drug, e.g.
active severe infection, unstable angina pectoris, cardiac arrhythmia, or severe heart failure/cardiac insufficiency
- 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
- Contraindications for cytarabine treatment according to the SPC
- Patient unable to comply with the protocol