Clinical trial NCT01716793: Risk-adapted Therapy for Adult Acute Myeloid Leukemia.
Official title: Risk Adapted Treatment for Primary AML in Adults up to the Age of 60 Years.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia, Myelocytic, Acute
Keywords: Primary AML
Risk-adapted treatment
Hematopoietic transplantation
CD34+ cell selection
Lead sponsor: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
Sponsor class: OTHER
First posted: 2012-10-30
Enrollment: 354
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In a protocol of treatment of AML used in 1994 for adults with AML up to the age of 50 years, the Spanish CETLAM group showed a complete remission rate 75 % using the combination of daunorubicin (60 mg/m2, 3 days) plus conventional dose cytarabine (100mg/m2/day in continuous infusion during 7 days) and etoposide (100mg/m2 IV/day 3 days). If idarubicin (10 mg/m2, 3 days) was administered instead of daunorubicin, the complete remission (CR) rate in adults up to 60 years was 75%. To improve the proportion of CRs and to decrease relapse rate appearing in 50% of patients, the phase II AML-99 trial includes intermediate dose-cytarabine during induction and risk-adapted post remission treatment based on the improvement in prognostic characterization of AML and the implementation of novel transplantation techniques.

Detailed description: Induction chemotherapy: idarubicin (12mg/m2/day intravenous), intermediate-dose cytarabine (500mg/m2/12h, intravenous) and etoposide (100mg/m2/day, intravenous) in 3+7+3 schedule. This induction therapy is repeated if complete remission (CR) is not achieved after the first course of treatment.

Consolidation therapy: mitoxantrone (12mg/m2/day, intravenous, days 4, 5 and 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 \[t(8;21), inv(16) or t(16;16)\] are treated with high-dose cytarabine (3g/m2/12h, intravenous, days 1, 3 and 5).
* Patients in intermediate cytogenetics group (normal karyotype and a single course to achieve the CR) receive an autologous peripheral blood stem cell (PBSC) transplant, regardless of having an HLA-identical sibling.
* The remaining patients are considered in the high-risk group and are treated with autologous or allogeneic PBSC transplantation depending on the availability of a sibling donor. In allotransplants, CD34+ cell selection of hematopoietic cells is performed.

Eligibility criteria: Inclusion Criteria:

* Patients with newly diagnosed AML, classified by FAB criteria
* Age not superior to 60 years
* Verbal informed consent for the chemotherapy and written for the mobilization and stem cell transplantation

Exclusion Criteria:

* Patients treated previously for its AML with other chemotherapy different from hydroxyurea
* Acute promyelocytic leukemia (M3)
* Chronic myeloid leukemia in blastic crisis
* Leukemias appearing after other myeloproliferative processes
* Leukemias surviving after myelodysplastic syndromes with more than 6 months of evolution
* Presence of other neoplastic disease in activity
* Secondary AML which had appeared after cured malignancies (for instance Hodgkin disease) and those who are still exposed to alkylant agents or radiation
* Renal and hepatic abnormal function with creatinine values and/or bilirubin two times higher than the normal threshold, except when this alteration could be attributed to the leukemia
* Patients with a fraction of ejection very low (inferior to 40%), symptomatic cardiac insufficiency or both
* Patients with a grave concomitant neurological or psychiatric disease
* Positivity of HIV (donor and/or receptor)

Primary outcomes:
measure: Complete remission rate.
timeFrame: 2 months.
measure: Disease free survival.
timeFrame: 4 years.
Secondary outcomes:
measure: Evaluations of minimal residual disease (MRD) by flow cytometry during and after treatment.
timeFrame: 4 years.
measure: Feasibility to mobilize and collect autologous PBSC after consolidation phase.
timeFrame: 6 months.
measure: Evaluations of the CD34+ cell selection procedure and allogeneic peripheral blood stem cell (PBSC)transplantation outcome.
timeFrame: 4 years.
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital 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: Joan Bargay
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: Jordi Esteve
city: Girona
country: Spain
facility: Hopital Universitari de Girona Dr. Josep Trueta
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Murcia
country: Spain
facility: Hospital General Universitario de Murcia
city: Tarragona
country: Spain
facility: Hospital Universitari Joan XXIII
city: Terrassa
country: Spain
facility: Mutua de Terrassa
city: Valencia
country: Spain
facility: Hospital Clínico 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: