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Risk-adapted, MRD-directed Therapy for Young Adults With Newly Diagnosed Acute Myeloid Leukemia. GIMEMA Protocol AML1310. EudraCT Number 2010-023809-36

Phase 2
18 Years
60 Years
Open (Enrolling)
Acute Myeloid Leukemia

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Trial Information

Risk-adapted, MRD-directed Therapy for Young Adults With Newly Diagnosed Acute Myeloid Leukemia. GIMEMA Protocol AML1310. EudraCT Number 2010-023809-36

The general objective of this study is that of setting up a multicentre, risk-adapted study
that relies on pre-treatment cytogenetic/genetic features and post-consolidation assessment
of Minimal Residual Disease (MRD) to establish the final risk assignment and treatment of
younger (≤ 60 years) patients with Acute Myeloid Leukemia (AML). Aim of this clinical trial
is to verify whether the delivery of a post remission therapy whose intensity is risk-driven
will improve the outcome in terms of both increased anti-leukemic efficacy and reduced
therapy-related toxicity.

All patients will receive induction and consolidation chemotherapy according to the Gruppo
Italiano Malattie EMatologiche dell'Adulto (GIMEMA) LAM99P protocol. After the first
consolidation, patients belonging to the low-risk category (core binding factor positive AML
without c-Kit mutations, NPM1 positive FLT3 negative AML) will receive autologous stem cell
transplantation, patients with high-risk features (adverse-risk karyotype, FLT3-ITD
mutations), will be assigned to allogeneic stem cell transplantation. Patients with FLT3-TKD
mutations or c-Kit mutated core binding factor positive AML and those belonging to the
intermediate-risk karyotype category will be stratified according to MRD by flow cytometry
and will receive risk-adapted treatment (autologous vs. allogeneic stem cell
transplantation). All patients who meet the criteria for high-risk definition will be
offered the allogeneic transplantation option regardless of the availability of a Human
Leukocyte Antigen (HLA) identical sibling. In fact, for those lacking a HLA identical
sibling all the other sources of hematopoietic stem cells (matched unrelated donor from
international registry, unrelated cord blood, family haploidentical donor) will be
considered. Autologous or allogeneic stem cell transplantation will be performed within 3
months from the end of consolidation therapy.

Inclusion Criteria:

- Signed written informed consent according to ICH/EU/GCP and national/local laws

- Patients aged between 18 and 60 years

- Patients previously untreated for their AML by other chemotherapeutic agents (with
the exception of no more than 7 days hydroxyurea (HU)), radiotherapy or more than 7
days corticosteroids

- Unequivocal diagnosis of untreated de novo AML according to WHO diagnostic criteria
(at least 20% blasts in the bone marrow), with FAB classification other than M3
(acute promyelocytic leukemia), documented by bone marrow aspiration (or biopsy in
case of dry tap) (not supervening after other myeloproliferative disease or
myelodysplastic syndromes of more than 6 months duration)

- WHO performance status 0-3

- Adequate renal (serum creatinine < 2 x the institutional Upper Limit of Normal (ULN))
and liver (total serum bilirubin < 2 x ULN; serum ALT and AST ≤ 3 x ULN) function,
unless considered due to organ leukemic involvement

- Left Ventricular Ejection Fraction (LVEF) >50%, as determined by echocardiogram

- Absence of severe concomitant neurological or psychiatric diseases and congestive
heart failure or active uncontrolled infection

- Absence of any psychological, familial, sociological and geographical condition
potentially hampering compliance with the study protocol and the follow-up schedule.

Exclusion Criteria:

- Patients aged less than 18 or more than 60 years

- Patients already treated for their AML by other chemotherapeutic agents (with the
exception of no more than 7 days HU), radiotherapy or more than 7 days

- Acute promyelocytic leukaemia

- Blast crisis of chronic myeloid leukaemia

- AML supervening after other myeloproliferative disease

- AML supervening after antecedent myelodysplastic syndromes of more than 6 months

- Other progressive malignant diseases. However, secondary AML following previously
cured malignancies may be included as well as secondary AML following previous
exposure to alkylating agents or radiation for other reason

- Inadequate renal or liver function (metabolic abnormalities > 3 times the normal
upper limit)

- Severe heart failure requiring diuretics

- Ejection fraction < 50%

- Uncontrolled infections

- WHO performance status = 4

- Severe concomitant neurological or psychiatric diseases

- Patients who are pregnant or adults of reproductive potential not employing an
effective method of birth control. Women of childbearing potential must have a
negative serum pregnancy test within 48 hrs prior to administration of chemotherapy.
Post-menopausal women must be amenorrhoeic for at least 12 months to be considered of
non-childbearing potential. Male and female patients must agree to employ an
effective barrier method of birth control throughout the study and for up to 3 months
following discontinuation of study drug.

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Treatment strategy in terms of Overall Survival (OS) at 24 months.

Outcome Description:

OS is defined as the time interval between the date of study entry and death for any cause; patients still alive will be censored at the time of the last follow-up.

Outcome Time Frame:

24 months from study entry.

Safety Issue:


Principal Investigator

Adriano VENDITTI, Pr.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Policlinico Tor Vergata di Roma


Italy: Ethics Committee

Study ID:




Start Date:

January 2012

Completion Date:

October 2015

Related Keywords:

  • Acute Myeloid Leukemia
  • acute myeloid leukemia
  • risk-adapted therapy
  • MRD-directed therapy
  • young adults
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid