A Randomized phase III trial for Primary Induction Therapy in AML Comparing a Dose-Dense Regimen S-HAM (sequential high dose cytosine arabinoside (AraC) and mitoxantrone) and Standard Double Induction with Allogeneic Stem Cell Transplantation as Preferred Consolidation Therapy
This is a multicenter, controlled, open label, prospective, parallel group 2-arm phase III trial (“Therapie-Optimierungsstudie”) with equal randomisation. Patients (≥18 years) with newly diagnosed AML (except APL and t(15;17)) will be randomized to receive induction treatment on either a dose-dense (S-HAM) or conventional double-induction schedule. The primary endpoint is the overall response rate.
Patients are randomly assigned to either S-HAM induction or standard double induction therapy. After achievement of CR, patients < 60 (- 70) years of age and intermediate or high risk of relapse and/or CRi only will preferentially undergo allogeneic stem cell transplantation. Patients ≥ 60 (- 70) years of age and patients < 60 (- 70) years of age with low risk of relapse will receive TAD-9 consolidation and three years of maintenance therapy.
Chemotherapy regimens are as follows (in patients ≥ 60 years cytarabine will only be given at 1g/m2 in the (S)-HAM regimens; dose capping performed for all drugs at 2 m2 BSA):
S-HAM: Cytarabine 3 g/m2 (1 g/m2 in patients ≥ 60 years) IV 3 hours twice daily days 1+2+8+9; Mitoxantrone 10 mg/m2 IV 1 hour days 3+4+10+11
TAD-9: Thioguanine 100 mg/m2 PO twice daily days 3-9; Cytarabine 100 mg/m2 IV 24 hours days 1+2; Cytarabine 100 mg/m2 IV 30 minutes twice daily days 3-8; Daunorubicin 60 mg/m2 IV 1 hour days 3-5
HAM: Cytarabine 3 g/m² (1 g/m2 in patients ≥ 60 years) IV 3 hours twice daily days 1-3; Mitoxantrone 10 mg/m² IV 1 hour days 3-5
TAD – HAM double induction for Patients < 60 (- 70) years: The second induction cycle with HAM starts on day 21 irrespective of blast count, unless prohibited by severe complications as stipulated by the protocol
HAM (– HAM) double induction for Patients ≥ 60 (- 70) years: The second induction cycle will only be given in case of ≥ 5% residual blasts in the bone marrow aspirate taken on day 16 and will start on day 21 unless prohibited by severe complications as stipulated by the protocol