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

NCT ID: NCT00909168

Last Updated: 2014-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2013-03-31

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Efficacy of FLAIMy

Group Type: EXPERIMENTAL

FLAIMy - Fluda, Ida, Ara-C, Mylotarg

Intervention Type: 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

Interventions

FLAIMy - 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

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Udine, Italy

OTHER

Sponsor Role: lead

Responsible Party

CANDONI ANNA

Division of Hematology, SM MISERICORDIA HOSPITAL

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

ANNA CANDONI, MD

Role: STUDY_DIRECTOR

UUNIVERSITY HOSPITAL, UDINE, ITALY

Locations

University Hospital, Udine

Udine, Italy, Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 29396857 (View on PubMed)

Other Identifiers

MYFLAI07

Identifier Type: -

Identifier Source: org_study_id