Risk Adapted Treatment for Primary Acute Myeloid Leukemia (AML)
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|ClinicalTrials.gov Identifier: NCT01723657|
Recruitment Status : Completed
First Posted : November 8, 2012
Last Update Posted : November 8, 2012
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.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia, Myelocytic, Acute||Drug: Ara-C Other: Autologous peripheral blood stem cell transplantation. Other: Allogeneic matched related or unrelated donor transplant. Drug: G-CSF Other: CD34+ selection. Other: Mylotarg purging before autologous PBSC transplantation||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||862 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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 Start Date :||October 2003|
|Actual Primary Completion Date :||March 2012|
|Actual Study Completion Date :||March 2012|
Risk-adapted postremission treatment.
Ara-C, G-CSF, Autologous peripheral blood stem cell transplantation, Allogeneic matched related or unrelated donor transplant, G-CSF Priming, CD34+ selection, Myeloablative or reduced intensity conditioning, Mylotarg purging before autologous PBSC transplantation.
Other: Autologous peripheral blood stem cell transplantation.
Other: Allogeneic matched related or unrelated donor transplant.
-Patients without favorable/intermediate characteristics.
Other Name: Filgastrim.
Other: CD34+ selection.
-Patients with adverse prognosis with allogeneic peripheral blood stem cell (PBSC)tranplantation, CD34+ cell selection of the inoculum was performed.
Other: Mylotarg purging before autologous PBSC transplantation
Patients without favorable/intermediate characteristics and without matched related donor.
- Complete remission rate (CRR) [ Time Frame: 2 months. ]Analyze the efficacy and toxicity of IDICE-G (idarubicin, intermediate doses of ara-C and etoposide) and G-CSF to achieve complete remission.
- Disease free survival (DFS). [ Time Frame: 4 years. ]
Analyze the disease free suvival of patients in remission, with a therapeutic strategy adjusted to the prognostic factors.
Mortality in remission after chemotherapy and/or peripheral blood stem cell tranplantation.
- Toxicity in patients over 60 years old. [ Time Frame: 4 years. ]Toxicity of the induction and intensification treatment in patients with more than 60 years old, in terms of unexpected adverse drug reaction, morbidity and mortality.
- Evaluation of minimal residual disease (MRD) by flow cytometry and/or molecular markers during and after treatment. [ Time Frame: 4 years. ]Study the immunophenotype characteristics and/or molecular markers at diagnosis, and during the different treatment phases.
- Feasibility of post-remission treatment in patients with 60 or more years old. [ Time Frame: 4 years. ]Study the effect of post-remission treatments in patients with more than 60 years to evaluate the success of consolidation treatments.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01723657
|Principal Investigator:||Jorge Sierra, MD||Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau|
|Study Chair:||Salut Brunet, MD||Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau|