Clinical trial NCT01723657: Risk Adapted Treatment for Primary Acute Myeloid Leukemia (AML)
Official title: Risk Adapted Treatment for Primary AML in Adults, Based on Genetics and Minimal Residual Disease (MRD) in Patients up to the Age of 70 Years.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia, Myelocytic, Acute
Keywords: Leukemia
Myeloid
Acute
Young
CETLAM
Lead sponsor: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
Sponsor class: OTHER
First posted: 2012-11-08
Enrollment: 862
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The AML-03 regimen investigates the addition of G-CSF priming to both induction and consolidation chemotherapies administrated in the previous AML-99 trial (NCT01716793) refines risk-stratification based on biological characterization also the AML-03 trial incorporates novel approaches for hematopoietic stem cell transplantation: such as Mylotarg™ "in vivo purging" in autografts, extends unrelated volunteers donors for allotransplants in high-risk patients, and introduces reduced intensity conditioning in patients with elder age (more than 50 years old).

The aims of these modifications are to analyse eficacy and toxicity of this induction and consolidation therapy and to analyse the disease free survival in patients who achieved complete response following a risk adjusted therapy.

Detailed description: Induction chemotherapy: idarubicin (12mg/m2/day intravenous, days 1, 3 and 5), intermediate-dose cytarabine (500mg/m2/12h, intravenous, days 1, 3 and 5) and etoposide (100mg/m2/day, intravenous, from day 1 to 3) as in AML-99 trial (NCT01716793), with the addition of subcutaneous G-CSF from day 0 to the last day of chemotherapy. This induction therapy is repeated if complete remission (CR) is not achieved after the first course of treatment.

Consolidation therapy (as in AML-99 trial): mitoxantrone (12mg/m2/day, intravenous, days 4 to 6) and intermediate-dose cytarabine (500mg/m2/12h from day 1 to 6).

Risk-stratification according to cytogenetics, courses to CR and availability of an HLA-identical sibling:

* Patients in the favorable cytogenetics group \[t(8;21), inv(16) or t(16;16)\] and Leukocyte index \<20 at diagnosis (LI=white blood cell count (WBC) x (blasts in bone marrow/100) are treated with one course of high-dose cytarabine (3g/m2/12h, intravenous, days 1, 3 and 5), but in case of LI\>20 at diagnosis the intention is to perform an autologous peripheral blood stem cell (PBSC) transplantation.
* Patients in intermediate risk group, with normal karyotype, a single course of induction chemotherapy to achieve the CR, the absence of adverse molecular features (FLT3-ITD or MLL-PTD) and low minimal residual disease levels after consolidation (MRD\<0,1%) receive an autologous PBSC transplant, regardless of having an HLA-identical sibling.
* The remaining patients defined as high-risk patients are treated with an allogeneic stem cell transplantation. Depending on the age, if the patient has an HLA-identical sibling donor, up to age of 50 years old it is performed with conventional conditioning therapy and positive selection of CD34+, older patients receive a reduced intensity conditioning regimen.
* Very high risk patients without a sibling are allocated to unrelated donor (9-10/10). Patients with adverse cytogenetics and/or FLT3-ITD without an adequate donor received Mylotarg™ as "in vivo purging" followed by an autologous PBSC transplantation.

Eligibility criteria: Inclusion Criteria:

* Patients with newly diagnosed AML, classified using OMS criteria.
* Patients with 70 years old or younger.

Exclusion Criteria:

* Patients previously treated for the AML with chemotherapy different from hidroxiurea.
* Acute promyelocytic leukemia with t(15;17).
* Cronic mieloid leukemia in blastic crisis.
* Leukemias that appear after other myeloproliferative processes.
* Leukemias that survive after myelodysplasic syndromes of more than 6 months of evolution.
* Presence of other neoplasic disease in activity.
* Secondary AML which appears after cured malignant disease (for instance, Hodgking disease), and those who are still exposed to alkilant agents or radiation.
* Abnormal renal and hepatic functions with creatinin and/or bilirrubine 2 times higher than the normal threshold, except when the alteration should be attributed to the leukemia.
* Patient with an ejection fraction below 40%, symptomatic cardiac deficiency or both.
* Patients with neurological or concomitant psychiatric disease.
* Positivity by HIV.

Primary outcomes:
measure: Complete remission rate (CRR)
timeFrame: 2 months.
measure: Disease free survival (DFS).
timeFrame: 4 years.
Secondary outcomes:
measure: Toxicity in patients over 60 years old.
timeFrame: 4 years.
measure: Evaluation of minimal residual disease (MRD) by flow cytometry and/or molecular markers during and after treatment.
timeFrame: 4 years.
measure: Feasibility of post-remission treatment in patients with 60 or more years old.
timeFrame: 4 years.
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: L'Hospitalet del Llobregat
country: Spain
facility: ICO Hospital Universitari de Bellvitge
state: Barcelona
city: A Coruña
country: Spain
facility: Hospital A Coruña
state: Coruña
city: Palma de Mallorca
country: Spain
facility: Hospital Universitari Son Espases
state: Mallorca
city: Palma de Mallorca
country: Spain
facility: Hospital Universitari Son Dureta
state: Mallorca
city: Tortosa
country: Spain
facility: Hospital Verge de la Cinta
state: Tarragona
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Centro Medico Teknon
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Girona
country: Spain
facility: Hopital Universitari de Girona Dr. Josep Trueta
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Murcia
country: Spain
facility: Hospital General Universitario de Murcia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Tarragona
country: Spain
facility: Hospital Universitari Joan XXIII
city: Terrassa
country: Spain
facility: Mutua de Terrassa
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valladolid
country: Spain
facility: Hospital Universitario Rio Hortega
Study officials:
affiliation: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
name: Jorge Sierra, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
name: Salut Brunet, MD
role: STUDY_CHAIR
References: