Risk-adapted Therapy for Adult Acute Myeloid Leukemia.

Study Overview
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Brief Summary
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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
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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.

Official Title
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Risk Adapted Treatment for Primary AML in Adults up to the Age of 60 Years.

Conditions
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Leukemia, Myelocytic, Acute

Intervention / Treatment
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* Drug: Ara-C
* Other: Autologous transplantation
* Other: Allogeneic HLA-identical sibling transplantation
* Other: CD34+ selection


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Risk-adapted postremission treatment<br>Ara-C, autologous transplantation, Allogeneic HLA-identical sibling transplantation depending on risk factors (cytogenetics, courses to CR)and availability of an HLA-identical sibling, CD34+ selection. | Drug: Ara-C<br>* Intermediate dose during induction phase to remission. High-dose during consolidation phase in patients with favorable cytogenetics.<br>Other: Autologous transplantation<br>* In patients with normal karyotype and one cycle of chemotherapy to achieve complete remission. In patients with other cytogenetics without HLA-Identical sibling.<br>Other: Allogeneic HLA-identical sibling transplantation<br>* 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.<br>Other: CD34+ selection<br>* In allotransplants, it is performed a CD34+ cell selection of peripheral blood stem cell transplantation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission rate. | Analyze the efficacy and toxicity of IDICE (idarubicin, intermediate doses of ara-C and etoposide) to achieve complete remission. | 2 months. | 
| Disease free survival. | Analyze the disease free survival (DFS)of patients in remission, with a therapeutic strategy adjusted to the prognostic factors. | 4 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluations of minimal residual disease (MRD) by flow cytometry during and after treatment. | Study of the immunophenotypic characteristics of the leukemic population at diagnosis and evaluation of MRD during different treatment phases and follow-up. | 4 years. | 
| Feasibility to mobilize and collect autologous PBSC after consolidation phase. | Evaluation of mobilization failures. | 6 months. | 
| Evaluations of the CD34+ cell selection procedure and allogeneic peripheral blood stem cell (PBSC)transplantation outcome. | CD34+ cell selection from PBSC of HLA-identical siblings. Conditioning regimen. Infusion and post-transplant follow-up. | 4 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary AML, Risk-adapted treatment, Hematopoietic transplantation, CD34+ cell selection