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

NCT00909168 | Completed Phase 2 DMC

• 1 other identifier: MYFLAI07
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Myeloid Leukemia

Keywords

Induction chemotherapy; Fludarabine; Gemtuzumab Ozogamicin

Outcome Measures

Primary Outcomes (2)

• Feasibility, Efficacy (CR+PR rate) and Toxicity of FLAI + Gemtuzumab-Ozogamicin.

  one year

• RFS, DFS and OS.

  one year

Secondary Outcomes (3)

• 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

Study Arms (1)

Efficacy of FLAIMy

EXPERIMENTAL

Drug: FLAIMy - Fluda, Ida, Ara-C, Mylotarg

Interventions

FLAIMy - Fluda, Ida, Ara-C, Mylotarg DRUG

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

Efficacy of FLAIMy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Udine, Italy: lead

Study Sites (1)

University Hospital, Udine

Udine, Italy, 33100, Italy

Location

Related Publications (1)

• Candoni A, Papayannidis C, Martinelli G, Simeone E, Gottardi M, Iacobucci I, Gherlinzoni F, Visani G, Baccarani M, Fanin R. Flai (fludarabine, cytarabine, idarubicin) plus low-dose Gemtuzumab Ozogamicin as induction therapy in CD33-positive AML: Final results and long term outcome of a phase II multicenter clinical trial. Am J Hematol. 2018 May;93(5):655-663. doi: 10.1002/ajh.25057. Epub 2018 Mar 2.

  PMID: 29396857 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Idarubicin; Cytarabine; Gemtuzumab

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Calicheamicins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• ANNA CANDONI, MD

  UUNIVERSITY HOSPITAL, UDINE, ITALY

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Division of Hematology, SM MISERICORDIA HOSPITAL

Study Record Dates

• First Submitted: May 26, 2009
• First Posted: May 27, 2009
• Study Start: March 1, 2008
• Primary Completion: May 1, 2009
• Study Completion: March 1, 2013
• Last Updated: May 6, 2014

Record last verified: 2014-05

Locations

IT (1)