DaunoXome + Ara-C vs Daunorubicin + Ara-C in Elderly AML
Condition: AML; Elderly
Study type: Interventional
Phase: Phase 3

Summary: 
      Overall results in the treatment of middle aged adults acute myelogenous leukemia (AML) are
      substantially improved in the last decade, with complete remission (CR) rates established to
      values of 70 to 80per cent and also encouraging long-term outcome, especially in patients who
      can tolerate intensified post remissional treatment strategies. On the contrary, there has
      been little progress in the treatment of older patients. In these patients the response rate
      generally range between 40 and 60per cent, and overall survival at 2 years is often less than
      10 per cent.

      Usually, a combination of anthracyclines daunomycin DNR or doxorubicin and cytarabyne Ara-C
      has been utilized for the remission-induction treatment, with schedules similar to those
      utilized in younger cases, for patients eligible to intensive treatments. Variation of the
      dose of DNR has not brought any significant benefit. The EORTC HOVON randomized trial AML9
      compared two drugs in induction for previously untreated patients. DNR versus Mithoxantrone
      (MTZ). MTZ induction therapy produces a slightly better CR rate than DNR-containing regimen
      (47per cent vs 38per cent, P equals 0.069), without any significant effect on remission
      duration and survival. The DFS probability between the two treatment arms was not different.
      The median DFS estimates were 39 weeks in both groups. The DFS rate at 5 years was 8per cent.
      Also the duration of survival was similar (p equals 0.23) in the two treatment groups. Median
      survival estimates were 36 weeks (DNR) and 39 weeks (MTZ). The percentage of patients still
      alive at 5 years were 6per cent and 9per cent respectively.
    

Detailed description: 
      It can be stated that single agent DaunoXome seems associated with a level of anti-leukemic
      activity at least equivalent to the conventional drugs available. In addition, the safety
      profile of DaunoXome either as a single agent either as a combination with Ara-C seems
      improved with respect to the conventionally administered anthracyclines. Therefore, it seems
      warranted to further explore the anti-leukemic activity, the toxicity and the long term
      results of DaunoXome as a treatment for AML in association with Ara-C against the parent
      compound daunorubicin. In particular, we propose a study to evaluate standard 3+7 schedule
      versus the same schedule with DaunoXome instead of daunorubicine as front line treatment in
      AML patients older than 60 years. Patients achieving a CR will receive a consolidation cycle
      with the same drugs at the same doses. After consolidation, patients in CR will be randomized
      to receive a maintenance treatment with low-dose Ara-C plus Atra versus no treatment.
    

Intervention name(s): DaunoXome; Daunorubicine
Intervention type(s): Drug; Drug
Intervention MeSH terms: Daunorubicin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: AML; elderly; DaunoXome