Leukemia, Myelocytic, Acute
Conditions
Keywords
Primary AML, Risk-adapted treatment, Hematopoietic transplantation, CD34+ cell selection
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.
Interventions
DRUGAra-C
* Intermediate dose during induction phase to remission. * High-dose during consolidation phase in patients with favorable cytogenetics.
* In patients with normal karyotype and one cycle of chemotherapy to achieve complete remission. * In patients with other cytogenetics without HLA-Identical sibling.
OTHERAllogeneic HLA-identical sibling transplantation
* Patients without favorable or normal karyotype(and one course to CR). * Patients with normal karyotype who need two cycles of chemotherapy to achieve CR, and other cytogenetics.
OTHERCD34+ selection
In allotransplants, it is performed a CD34+ cell selection of peripheral blood stem cell transplantation.
Sponsors
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete remission rate. | 2 months. | Analyze the efficacy and toxicity of IDICE (idarubicin, intermediate doses of ara-C and etoposide) to achieve complete remission. |
| Disease free survival. | 4 years. | Analyze the disease free survival (DFS)of patients in remission, with a therapeutic strategy adjusted to the prognostic factors. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluations of minimal residual disease (MRD) by flow cytometry during and after treatment. | 4 years. | Study of the immunophenotypic characteristics of the leukemic population at diagnosis and evaluation of MRD during different treatment phases and follow-up. |
| Feasibility to mobilize and collect autologous PBSC after consolidation phase. | 6 months. | Evaluation of mobilization failures. |
| Evaluations of the CD34+ cell selection procedure and allogeneic peripheral blood stem cell (PBSC)transplantation outcome. | 4 years. | CD34+ cell selection from PBSC of HLA-identical siblings. Conditioning regimen. Infusion and post-transplant follow-up. |
Countries
Spain
Outcome results
None listed