A Phase II Study on Allogeneic Stem Cell Transplantation in Patients With Active Acute Leukemia
Condition: Acute Leukemia
MeSH terms: Leukemia; Acute Disease
Study type: Interventional
Phase: Phase 2

Summary: 
      The experimental treatment consists in the application of a therapeutic strategy of
      allogeneic transplantation as a potential curative procedure in a population of patients with
      chemoresistant acute leukemias.

      Therapeutic intervention, namely the conditioning regimen as well as GVHD prophylaxis, are
      based on regimens currently in standard use in the context of allogeneic transplantation.
    

Detailed description: 
      The experimental treatment consists in the application of a therapeutic strategy of
      allogeneic transplantation using either a Marrow Unrelated Donor (MUD) or a Cord Blood (CB)
      unit or a family Haploidentical (Haplo) donor as a potential curative procedure in a
      population of patients with chemoresistant acute leukemias for increase the overall survival
      in this patients.

      Therapeutic intervention, namely the conditioning regimen as well as GVHD prophylaxis, are
      based on regimens currently in standard use in the context of allogeneic transplantation.

      The Data Safety Monitoring Board (DSMB) in collaboration with the Steering Committee (SC)
      will make periodic monitoring to ensure the safety of patients enrolled in to the study. In
      particular, DSMB will check the periodic safety reports of serious adverse events, the
      primary or secondary graft failure and treated related mortality (TRM) data generated by the
      Data Management Center. A safety report will be generated every 30 enrolled patients
      completed 100 days of follow-up.

      The population for analysis in the trial will be the Intention to Treat (ITT) population. All
      patients enrolled in the study will be included in the ITT analysis.

      This study will explore the feasibility, safety and efficacy of allogeneic stem cell
      transplantation from unrelated, cord-blood and haploidentical donor in patients with an
      active leukemia. Due to the lack of detailed information from literature and the absence of
      alternative curative options in this patient population, criteria for sample size assessment
      do not refer to a formal statistical power calculation. Therefore, GITMO will promote
      enrollment of all patients with active leukemia eligible to allogeneic SCT in all Italian
      centres with the aim to collect outcome variables in ITT in the widest and most
      representative cohort of this specific patient population.

      The choice of 80 patients transplanted is based on feasibility reasons and the expected
      patient population with these characteristics referred to the main Italian Transplant Centres
      in two year. GITMO survey data on transplant activity points to an estimated accrual of 40
      patients per year over a 24 months enrolment period. Criteria for defining sample size do not
      follow statistical power estimates in order to demonstrate difference between the alternative
      donor options.
    

Intervention name(s): allogeneic transplant
Intervention type(s): Procedure
Intervention description(s): Allogenic transplant using either a Marrow Unrelated Donor or a Cord Blood unit or a family Haploidentical donor.
The conditioning regimen in standard use is:
Thiotepa (Tepadina) i.v. 5 mg/kg/daily (total dose 10 mg/kg) day -7 and -6;
Busulfan (Busilvex) i.v. 3,2 mg/kg/day (total dose 9,6 mg/kg) as a single daily dose day -5, -4, -3;
Fludarabine i.v. 50 mg/m2 (total dose150 mg/m2) day -5, -4, -3.
Primary antifungal prophylaxis is Micafungin 50 mg/die i.v. (1 mg/kg if <40 kg) day 0 to engraftment. After engraftment continue antifungal prophylaxis according to local practice.
Other intervention name(s): Marrow Unrelated or Cord Blood or family Haploidentical donor
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Active acute leukemia; PIF; Allogeneic transplant; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Marrow Unrelated Donor; Cord Blood; Family Haploidentical donor