Multicenter, Prospective, Open-label, Single-arm, Phase I-II Clinical Trial to Analyze Induction Therapy With a Combination of Fludarabine, Idarubicin, Cytarabine, G-CSF and Plerixafor for the Treatment of Young Patients With Relapsed or Refractory AML
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
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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Efficacy in terms of number of complete responses
Spain: Ministry of Health and Consumption