Risk-adapted Therapy for Primary Acute Myeloid Leukemia
Condition: Leukemia, Myeloid, Acute
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Interventional
Phase: Phase 2

Summary: 
      The AML-12 study investigates the efficacy and toxicity of standard induction chemotherapy
      with idarubicin and cytarabine (IC) with G-CSF priming followed by a risk-adapted post
      remission therapy for patients up to the age of 70 diagnosed with de novo acute myeloid
      leukemia (AML).

      Modifications from the previous protocol AML-03 (NCT01723657) include removal of etoposide in
      induction, limitation of the GCSF priming to the induction phase and categorization of post
      remission therapy (stem cell transplant or 2 high dose cytarabine consolidations) according
      to diagnostic genetics as well as post-remission clearance of measurable residual disease.

      The aims of these modifications are to improve the overall survival and leukemia free
      survival of acute myeloid leukemia patients with a risk-adapted approach.
    

Detailed description: 
      Induction chemotherapy: Idarubicin (12mg/m2/day intravenous, days 1-3), Low-dose cytarabine
      (200mg/m2/day, intravenous in continuous infusion, days 1-7) and G-CSF priming 150mcg/m2/day,
      subcutaneous from day 0 to the last day of chemotherapy if white blood cell count (WBC)
      <30x10E9/L.

      This induction chemotherapy can be repeated twice in the case of partial response (PR) to
      achieve complete response (CR).

      Once CR is achieved (with one or two induction cycles), all patients receive a consolidation
      course with high-dose cytarabine (3000mg/m2/12h days 1, 3 and 5) and pegfilgrastim 6mg on day
      6.

      After this, patients will be allocated to the different risk groups as follows:

        -  Favorable risk group [patients with t(8;21)(q22;q22)/RUNX1/RUNX1T1, inv(16)(p12;q22) or
           t(16;16)/CBFB/MYH11; Intermediate risk cytogenetics (MRC 2010) and NPM1 mutation with
           FLT3 wild type or low ratio of FLT3 internal tandem duplication (ITD)/wild type (<0.5);
           or CEBPA biallelic mutation]. Patients in this group will receive 2 additional courses
           of consolidation therapy

        -  Intermediate risk group [Intermediate risk cytogenetics (MRC 2010) without NPM1
           mutations, FLT3-ITD, or CEBPA biallelic mutation]. Patients in this group receive an
           allogeneic stem cell transplant in first CR. Patients without an available donor can be
           autografted per center decision

        -  Adverse risk group [Adverse risk cytogenetics (MRC 2010), intermediate cytogenetics with
           FLT3-ITD without NPM1 mutation or NPM1-FLT3-ITD high ratio or MLL rearrangement; any
           favorable or intermediate risk patients with positive MRD following 1 (intermediate) or
           2 (favorable) consolidation courses]. Intention to treat of those patients is allogeneic
           stem cell transplant from any source.
    

Intervention name(s): Idarubicin; Ara-C; G-CSF; Allogeneic matched or unrelated donor transplant.; Autologous peripheral blood stem cell transplant; Measurable residual disease
Intervention type(s): Drug; Drug; Drug; Procedure; Procedure; Procedure
Intervention description(s): 12 mg/m2/day; intravenous, administration at induction phase, days 1 to 3.; 200mg/m2/day, intravenous at induction phase; days 1-7.
- High dose during consolidation phase. In patients up to 60 years 3g/m2/12hours days 1,3,5, and patients 60 to 70 years: 1.5g/m2/12hours days 1,3,5.; Administration at induction phase to remission days 1 to 7. G-CSF will not be initiated if the leukocyte count is over 30x10e9/L at diagnosis or will be interrupted if the leukocyte count during treatment arises 30x10e9/L.
Administration at consolidation phase day 7.; To be performed in patients in the intermediate or adverse risk groups.; To be considered in patients in the intermediate risk group without an available allogeneic donor and negative measurable residual disease, per center decision.; To be performed either with molecular monitoring or, if not applicable, by flow cytometry. Pre-stablished cut-off values are defined for decision-making.
Other intervention name(s): Ida; HDAC; Pegfilgrastim; MRD
Intervention MeSH terms: Idarubicin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Leukemia; Myeloid