A Randomized, Risk and Age Adapted Comparison of the Dose-Dense Regimen S-HAM (sequential high dose cytosine arabinoside and mitoxantrone) versus Standard Double Induction for Initial Chemotherapy of Adult Patients with Acute Myeloid Leukemia

INTERVENTION: Product Name: Cytarabine (AraC) Pharmaceutical Form: Suspension for injection INN or Proposed INN: Cytarabine CAS Number: 147‐94‐4 Current Sponsor code: Cytarabine (AraC) Concentration unit: gm/m2 gram(s)/square meter Concentration type: range Concentration number: 1‐3 Product Name: Mitoxantrone Pharmaceutical Form: Solution for injection INN or Proposed INN: Mitoxantrone Hydrochloride CAS Number: 70476‐82‐3 Current Sponsor code: Mitoxantrone Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 10‐ Product Name: Thioguanine Pharmaceutical Form: Tablet INN or Proposed INN: Tioguanine CAS Number: 154‐42‐7 Current Sponsor code: Thioguanine Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 100‐ Product Name: Daunorubicin Pharmaceutical Form: Powder for infusion INN or Proposed INN: Daunorubicin Hydrochloride CAS Number: 23541‐50‐6 Current Sponsor code: Daunorubicin Concentration unit: mg/m2 milligram(s)/square meter Concentration type: equal Concentration number: 60‐ CONDITION: Adult patients (=18 years) with newly‐diagnosed acute myeloid leukemia (AML) ‐ except acute promyelocytic leukemia (APL) and t(15;17) ; MedDRA version: 14.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) PRIMARY OUTCOME: Main Objective: Overall response rate (ORR), aiming at a 15% increase in the CR (complete remission)/CRi (incomplete peripheral recovery) rate by S‐HAM induction versus conventional double induction [TAD – HAM for younger patients, HAM (‐ HAM) for elderly patients]. Primary end point(s): Overall response rate (ORR) after induction therapy in patients with newly diagnosed acute myeloid leukemia (AML). ORR comprises complete remission (CR) and CR with incomplete peripheral recovery (CRi). Secondary Objective: • Duration of critical neutropenia and hospitalization; • Event free, relapse free and overall survival; • Remission duration; • Treatment associated side effects INCLUSION CRITERIA: • Patients with newly diagnosed AML (except acute promyelocytic leukemia and t(15;17)) according to the WHO classification • Age =18 years • Written informed consent. 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