Risk Adapted Treatment for Primary Acute Myeloid Leukemia (AML)
Condition: Leukemia, Myelocytic, Acute
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Interventional
Phase: Phase 2

Summary: 
      The AML-03 regimen investigates the addition of G-CSF priming to both induction and
      consolidation chemotherapies administrated in the previous AML-99 trial (NCT01716793) refines
      risk-stratification based on biological characterization also the AML-03 trial incorporates
      novel approaches for hematopoietic stem cell transplantation: such as Mylotarg™ "in vivo
      purging" in autografts, extends unrelated volunteers donors for allotransplants in high-risk
      patients, and introduces reduced intensity conditioning in patients with elder age (more than
      50 years old).

      The aims of these modifications are to analyse eficacy and toxicity of this induction and
      consolidation therapy and to analyse the disease free survival in patients who achieved
      complete response following a risk adjusted therapy.
    

Detailed description: 
      Induction chemotherapy: idarubicin (12mg/m2/day intravenous, days 1, 3 and 5),
      intermediate-dose cytarabine (500mg/m2/12h, intravenous, days 1, 3 and 5) and etoposide
      (100mg/m2/day, intravenous, from day 1 to 3) as in AML-99 trial (NCT01716793), with the
      addition of subcutaneous G-CSF from day 0 to the last day of chemotherapy. This induction
      therapy is repeated if complete remission (CR) is not achieved after the first course of
      treatment.

      Consolidation therapy (as in AML-99 trial): mitoxantrone (12mg/m2/day, intravenous, days 4 to
      6) and intermediate-dose cytarabine (500mg/m2/12h from day 1 to 6).

      Risk-stratification according to cytogenetics, courses to CR and availability of an
      HLA-identical sibling:

        -  Patients in the favorable cytogenetics group [t(8;21), inv(16) or t(16;16)] and
           Leukocyte index <20 at diagnosis (LI=white blood cell count (WBC) x (blasts in bone
           marrow/100) are treated with one course of high-dose cytarabine (3g/m2/12h, intravenous,
           days 1, 3 and 5), but in case of LI>20 at diagnosis the intention is to perform an
           autologous peripheral blood stem cell (PBSC) transplantation.

        -  Patients in intermediate risk group, with normal karyotype, a single course of induction
           chemotherapy to achieve the CR, the absence of adverse molecular features (FLT3-ITD or
           MLL-PTD) and low minimal residual disease levels after consolidation (MRD<0,1%) receive
           an autologous PBSC transplant, regardless of having an HLA-identical sibling.

        -  The remaining patients defined as high-risk patients are treated with an allogeneic stem
           cell transplantation. Depending on the age, if the patient has an HLA-identical sibling
           donor, up to age of 50 years old it is performed with conventional conditioning therapy
           and positive selection of CD34+, older patients receive a reduced intensity conditioning
           regimen.

        -  Very high risk patients without a sibling are allocated to unrelated donor (9-10/10).
           Patients with adverse cytogenetics and/or FLT3-ITD without an adequate donor received
           Mylotarg™ as "in vivo purging" followed by an autologous PBSC transplantation.
    

Intervention name(s): Ara-C; Autologous peripheral blood stem cell transplantation.; Allogeneic matched related or unrelated donor transplant.; G-CSF; CD34+ selection.; Mylotarg purging before autologous PBSC transplantation
Intervention type(s): Drug; Other; Other; Drug; Other; Other
Intervention description(s): Intermediate dose during induction phase to remission.
High dose during consolidation phase in patients with favorable cytogenetics and leukocyte index below 20.; In patients with favorable cytogenetics with a Leukocyte index above 20.
Patients with normal karyotype, and one cycle of chemotherapy to achieve complete remission, without adverse molecular and/or minimal residual disease (MRD) characteristics, regardless availability of a matched donor.; -Patients without favorable/intermediate characteristics.; Administration at induction phase to remission, days 0 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 treatmen arises 30x10e9/L.
Administration at consolidation phase, days 4 to 6 (3 doses). G-CSF will be interrupted if the leukocyte count during treatment arises 30x10e9/L.; -Patients with adverse prognosis with allogeneic peripheral blood stem cell (PBSC)tranplantation, CD34+ cell selection of the inoculum was performed.; Patients without favorable/intermediate characteristics and without matched related donor.
Other intervention name(s): Filgastrim.
Intervention MeSH terms: Gemtuzumab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Leukemia; Myeloid; Acute; Young; CETLAM