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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).

Phase 1/Phase 2
18 Years
Not Enrolling
Acute Myeloid Leukemia

Thank you

Trial Information

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.

Inclusion Criteria:

- The patient must, according with investigator criteria,be able to comply with all the
protocol requirements.

- The patient must sign voluntarily the informed consent before the performance of any
study related procedure not part of usual medical care, with the knowledge that can
leave the study the moment he/she wants, without prejudice to later medical care.

- Age ¡Ý 18 years old.

- Patient must be diagnosed with AML according World Health Organization (WHO)18
criteria (see Appendix 7).

- Patient with refractory AML after standard therapy, or relapsed AML after standard
therapy or hematopoietic progenitors transplant (autologous or allogenic).

- Patient has a ECOG performance status <= 2 (see Appendix 5).

- Patient has the following laboratory values before Baseline visit:

1. Platelet count ≥ 30000/mm3 (transfusion allowed), hemoglobin ≥ 8 g/dl
(transfusion allowed) and absolute neutrophil count ≥ 0.750/mm3. Lower values
are accepted if they are caused by bone marrow infiltration.

2. Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal.

3. Alanine transaminase (ALT): ≤ 2.5 x the upper limit of normal.

4. Total bilirubin: ≤1.5 x the upper limit of normal.

5. Serum creatinine value ≤ 2 mg/dl.

- Negative pregnant test for fertile females

Exclusion Criteria:

Prior Bortezomib therapy.

- Promyelocytic AML.

- Patient has > Grade 2 peripheral neuropathy within 14 days before enrollment.

- Fertile patient is not going to use a medical effective contraceptive method during
the trial.

- Patient has received other investigational drugs within 30 days before enrollment.

- Patient is known to be seropositive for the human immunodeficiency virus (HIV),
Hepatitis B surface antigen-positive or active hepatitis C infection.

- Patient had a myocardial infarction within 6 months of enrollment or has New York
Heart Association (NYHA) Class III or IV, heart failure, uncontrolled angina, severe
uncontrolled ventricular arrhythmias,or electrocardiographic evidence of acute
ischemia or active conduction system abnormalities.

- Patient is enrolled in another clinical research study and/or is receiving an
investigational agent for any reason.

- Pregnant or breast-feeding women.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

San Miguel Jesús, Dr

Investigator Role:

Study Chair

Investigator Affiliation:

PETHEMA Foundation


Spain: Ministry of Health

Study ID:

Nº EudraCT: 2005-004370-24



Start Date:

April 2008

Completion Date:

February 2013

Related Keywords:

  • Acute Myeloid Leukemia
  • Acute Myeloid Leukemia
  • Relapsed
  • Refractory
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid