Induction, Consolidation and Intensification Therapy for Patients Younger Than 66 Years With Previously Untreated CD33 Positive Acute Myeloid Leukemia (AML)

Study Overview
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Brief Summary
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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.

Official Title
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Induction, Consolidation and Intensification Therapy for Patients Younger Than 66 Years With Previously Untreated CD33 Positive Acute Myeloid Leukemia (AML)

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: FLAIMy - Fluda, Ida, Ara-C, Mylotarg


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Efficacy of FLAIMy<br> | Drug: FLAIMy - Fluda, Ida, Ara-C, Mylotarg<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility, Efficacy (CR+PR rate) and Toxicity of FLAI + Gemtuzumab-Ozogamicin. |  | one year | 
| RFS, DFS and OS. |  | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Induction chemotherapy, Fludarabine, Gemtuzumab Ozogamicin