Clinical trial NCT00909168: Induction, Consolidation and Intensification Therapy for Patients Younger Than 66 Years With Previously Untreated CD33 Positive Acute Myeloid Leukemia (AML)
Official title: Induction, Consolidation and Intensification Therapy for Patients Younger Than 66 Years With Previously Untreated CD33 Positive Acute Myeloid Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Acute Myeloid Leukemia
Keywords: Induction chemotherapy
Fludarabine
Gemtuzumab Ozogamicin
Lead sponsor: University Hospital, Udine, Italy
Sponsor class: OTHER
First posted: 2009-05-27
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Feasibility, Efficacy (CR+PR rate) and Toxicity of FLAI + Gemtuzumab-Ozogamicin.
timeFrame: one year
measure: RFS, DFS and OS.
timeFrame: one year
Secondary outcomes:
measure: Evaluation of Minimal Residual Disease by WT1 (and other biologic markers) expression and monitoring.
timeFrame: one year
measure: Evaluation of prognostic clinical relevance of biological features at onset.
timeFrame: one year
measure: Feasibility and outcome of consolidation with BMT.
timeFrame: one year
Other outcomes:
Locations:
city: Udine
country: Italy
facility: University Hospital, Udine
Study officials:
affiliation: UUNIVERSITY HOSPITAL, UDINE, ITALY
name: ANNA CANDONI, MD
role: STUDY_DIRECTOR
References:
citation: 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.