Acute Myeloid Leukemia
Conditions
Keywords
Induction chemotherapy, Fludarabine, Gemtuzumab Ozogamicin
Brief summary
This is a prospective, open, non-randomized, non-controlled, phase II, clinical trial for treatment of newly diagnosed AML patients, younger than 66 years. Trial is based on: * INDUCTION: FLAI + Gemtuzumab-Ozogamicin (FLAI-GO). * CONSOLIDATION: Intermediate dose AraC + IDA (IDAC+IDA) +/- one course of high dose AraC (HDAC) * INTENSIFICATION: Allo-BMT, ASCT * MAINTENANCE: AraC a) Primary endpoints: * Feasibility, Efficacy (CR+PR rate) and Toxicity of FLAI + Gemtuzumab-Ozogamicin. * RFS, DFS and OS. b) Secondary endpoints: * Evaluation of Minimal Residual Disease by WT1 (and other biologic markers) expression and monitoring. * Evaluation of prognostic clinical relevance of biological features at onset. * Feasibility and outcome of consolidation with BMT.
Interventions
DRUGFLAIMy - Fluda, Ida, Ara-C, Mylotarg
FLUDARABINE: 25 mg/m2/day, 250 FS in 30', start h 9 - 1, 2, 3, 4, 5 ARABINOSYL-CYTOSINE (Cytarabine): 2 g/m2/day, 500 FS in 3 h, start h 13 - 1, 2, 3, 4, 5 IDARUBICIN: 10 mg/m2/day, 100 FS in 1 h, start h 16 - 1, 3, 5 GEMTUZUMAB OZOGAMICIN (Mylotarg): 5 mg, single dose 500 FS in 4 h - 6
Sponsors
University Hospital, Udine, Italy
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-65 years. * WHO PS grade 0-2 (Appendix B) or Karnofsky \> 70. * AML according to the new WHO criteria, i.e., % of BM blasts ≥ 20%. NB. this % should be assessed on a BM aspiration or on a BM biopsy * All FAB subtypes except M3. * CD33 positivity (\> 20%). It is mandatory to perform an immunotyping of the BM blasts in particular the determination of CD33 positivity, which will be used as a inclusion factor. * Previously untreated (except ≤ 14 days of Hydroxyurea) primary or secondary AML (including AML after MDS). * Adequate renal and liver function, i.e., creatinine \< 2 mg/dl and bilirubin, ALT/AST ≤ 3 times the upper limit of normal. * Written informed consent
Exclusion criteria
* Blast crisis of chronic myeloid leukemia. * AML supervening after other myeloproliferative diseases. * AML de novo or secondary previously pretreated. * Concomitant malignant disease. * Active central nervous system (CNS) leukemia. * Active uncontrolled infection \[NB severe systemic infection should be excluded\]. * Concomitant severe cardiovascular disease, i.e., arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease. * Cardiac ejection fraction of 50% or less. * Severe pulmonary dysfunction (CTC grade 3-4). * Severe concomitant neurological or psychiatric disease. * History of alcohol abuse. * HIV positivity. * Pregnancy. * Man and woman not agreeing to the adequate contraceptive precautions during study period and for at last 24 months after stop of therapy. * Any psychological, familiar, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Feasibility, Efficacy (CR+PR rate) and Toxicity of FLAI + Gemtuzumab-Ozogamicin. | one year |
| RFS, DFS and OS. | one year |
Secondary
| Measure | Time frame |
|---|---|
| Evaluation of Minimal Residual Disease by WT1 (and other biologic markers) expression and monitoring. | one year |
| Evaluation of prognostic clinical relevance of biological features at onset. | one year |
| Feasibility and outcome of consolidation with BMT. | one year |
Countries
Italy
Outcome results
None listed