A Phase I/II National, Open-label, Multicenter Study of Bortezomib (Velcade) in Combination With FLAG-IDA (VFLAG- IDA) in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML).
Initially a phase I will be performed to determine the appropriate dose of Cytarabine to be
used in Flag-Ida regimen in combination with Velcade; for that reason, first 9 patients will
be distributed to 3 different cohorts with 3 patients in each cohort, which will be treated
at each Cytarabine dose level (200 mg/m2-500 mg/m2-1000 mg/m2)in combination with the other
drugs from Flag scheme and the fixed dose of Velcade at 1,3 mg/m2.
Once the appropriate Cytarabine dose is determined,the recruitment will be completed with 40
patients and evaluations and visits program will be realized in three periods:
Pre-treatment, Treatment and Follow-up.
The Pre-treatment includes Screening and baseline visits. After providing informed consent,
patients will be evaluated for study eligibility.
Eligible patients included in the study will receive the first cycle, which consist of
Fludarabine, Cytarabine and Idarubicin in combination with 2 times per week of Velcade
administration. Each 28-day treatment, patients will be evaluated, and in absence of disease
progression or unacceptable toxicity, patients will start second cycle with Bortezomib in
monotherapy two times per week followed by a 10 days rest period. That is, patients who
response with acceptable toxicity will receive the combined sequential scheme twice (as
induction and consolidation).
Patients will be evaluated the day 1 of each cycle,during the treatment period, in order to
know the response before carrying on the treatment. Once the Treatment period is completed,
patients will be evaluated during the Follow-up period, one monthly visit in year 1, and
every 3 months for 3 next years. On each center criteria, autologous/allogeneic transplant
can be planned depending on age and HLA identical sibling donor make it possible: it will be
done following the sequential scheme (Velcade-Flag-Ida and Velcade in monotherapy); if the
patient is not candidate for a transplant or has no donor, he/she will receive 2 sequential
Safety will be evaluated through all adverse events monitoring, physical exploration, vital
signs, hematimetric and biochemical analysis. The treatment response will be evaluated using
Cheson's standardized criteria, and MRD impact will be necessary evaluated the day 1 of each
new cycle before to carry on the treatment.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Efficacy (in order to evaluate the response) of a sequential treatment scheme of Bortezomib in combination with Fludarabine,Cytarabine and Idarubicin continued with Bortezomib monotherapy for patients with relapsed or refractory AML ≥18 years old.
San Miguel Jesús, Dr
Spain: Ministry of Health
Nº EudraCT: 2005-004370-24