Induction, Consolidation and Intensification Therapy for Patients Younger Than 66 Years With Previously Untreated CD33 Positive Acute Myeloid Leukemia (AML) (MYFLAI07)

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.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: FLAIMy - Fluda, Ida, Ara-C, Mylotarg

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Italy
  • Udine, Italy, 33100
    • University Hospital, Udine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Efficacy of FLAIMy	Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University Hospital, Udine, Italy
• Investigators: Study Director: ANNA CANDONI, MD, UUNIVERSITY HOSPITAL, UDINE, ITALY

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: May 26, 2009
• First Submitted That Met QC Criteria: May 26, 2009
• First Posted (Estimate): May 27, 2009

Study Record Updates

• Last Update Posted (Estimate): May 6, 2014
• Last Update Submitted That Met QC Criteria: May 5, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Gemtuzumab Ozogamicin; Fludarabine; Induction chemotherapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Antineoplastic Agents; Antineoplastic Agents, Immunological; Gemtuzumab
• Other Study ID Numbers: MYFLAI07