Treatment of Relapsed or Refractory Acute Myeloblastic Leukemia
Condition: Acute Myeloblastic Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Second-line induction therapy with fludarabine, idarubicin, cytarabine,Granulocyte
      colony-stimulating factor (G-CSF) and plerixafor, in patients with relapsed or refractory
      Acute Myeloblastic Leukemia (AML) aged 65 or younger.
    

Detailed description: 
      This protocol corresponds to a multicenter, open-label, non-randomized, Phase I-II study
      designed to determine the safety and efficacy of the combination of plerixafor with
      chemotherapy in young patients with relapsed or refractory AML.

      The clinical trial is divided into pre-treatment and treatment periods (induction and
      consolidation cycle(s) and consists of two general phases: an initial Phase I in which
      escalating doses of plerixafor will be given to 4 groups, each with 3 patients; and a
      secondary Phase II in which an additional patient group will be treated with the maximum
      tolerated dose (MTD) from Phase I.

      In the pre-treatment period, all patients who provide written informed consent will be
      screened and any patients who meet all the inclusion and none of the exclusion criteria will
      be eligible for treatment.

      The patients who are finally included in the study should begin treatment within 7 days after
      signing the informed consent document (ICD). The pre-treatment period begins when the ICD is
      signed and enrollment occurs when the patient receives the first study drug of the treatment
      regimen (i.e., Day 1 of the induction cycle).

      In this study, the induction cycle will consist of fludarabine 30 mg/m2/day intravenously on
      days 1 to 4, idarubicin 10 mg/m2/day intravenously on days 1 to 3, cytarabine 2 g/m2/day
      intravenously on days 1 to 4, G-CSF 5 μg/kg/day subcutaneously from days 1 to 4, and
      plerixafor intravenously from days 1 to 4. The dose of plerixafor will be escalated over 4
      groups of three patients as follows: 240 μg/kg/day (120 μg/kg/12 h); 320 μg/kg/day (160
      μg/kg/12 h); 400 μg/kg/day (200 μg/kg/12 h); and 480 μg/kg/day (240 μg/kg/12 h). If MTD is
      observed with the first treatment dose of plerixafor the dose will be progressively
      deescalated to 160 μg/kg/day (80μg/kg/12 h) on a first deescalating level or 240 μg/kg/day in
      a single daily dose on a second deescalating level if no twice a day (BID) dose is tolerated.
      Patient enrollment will be expanded to a total of 55 patients using MTD. If patients do not
      achieve CR after one induction cycle they will leave the study and be followed according to
      routine clinical practice. Patients who achieve complete response (CR) who are eligible for
      allogeneic hematopoietic stem cell transplantation (HSCT) and have a donor will leave the
      trial and receive allogeneic HSCT and will be followed according to routine clinical
      practice. Patients who achieve CR and are not eligible for allogeneic HSCT or do not have a
      donor will receive two consolidations with cytarabine at 3 g/m2/12 hours on days 1, 3 and 5
      along with Granulocyte colony-stimulating factor (GCSF) at 5 μg/kg/day on days 1 to 5 and
      plerixafor at the same dose used in the induction cycle on days 1, 3 and 5, coinciding with
      the days that cytarabine is administered.

      In the context of this protocol, a treatment cycle is defined as the first day of the study
      drug administration regimens (Day 1) up to and including the day before the first day of the
      treatment cycle immediately afterwards. The treatment cycles will begin after Day 28 but no
      later than Day 85, counting from Day 1 of the treatment cycle immediately before.

      Patients will be assessed in the three days before each cycle (see Appendix A). Follow-up,
      outside the protocol in routine clinical practice, will be performed monthly during the first
      year and at least every three months during the second year; notwithstanding, visits may be
      more frequent at the discretion of each site or based on the clinical characteristics.

      All treatment cycles will be administered while the patient is hospitalized. Clinical
      procedures for the care of patients with acute leukemia require flexibility. However,
      deviations from the study treatment defined in this section must be prospectively discussed
      with the coordinator.
    

Intervention name(s): fludarabine; Idarubicin; cytarabine; G-CSF; plerixafor
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): 30 mg/m2/day intravenously on days 1 to 4; 10 mg/m2/day intravenously on days 1 to 3; 2 g/m2/day intravenously on days 1 to 4; 5 μg/kg/day subcutaneously from days 1 to 4; intravenously from days 1 to 4
Intervention MeSH terms: Cytarabine; Plerixafor; Fludarabine; Idarubicin
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment