- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01723657
Risk Adapted Treatment for Primary Acute Myeloid Leukemia (AML)
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.
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.
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Barcelona, Spain, 08003
- Hospital Del Mar
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Barcelona, Spain, 08036
- Hospital Clínic de Barcelona
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Barcelona, Spain, 08035
- Hospital Vall d'Hebron
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Barcelona, Spain, 08025
- Hospital de la Santa Creu i Sant Pau
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Barcelona, Spain, 08022
- Centro Médico Teknon
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Girona, Spain, 17007
- Hopital Universitari de Girona Dr. Josep Trueta
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Lleida, Spain, 25006
- Hospital Universitari Arnau de Vilanova
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Madrid, Spain, 28046
- Hospital Universitario La Paz
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Malaga, Spain, 29010
- Hospital Universitario Virgen de la Victoria
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Murcia, Spain, 30008
- Hospital General Universitario de Murcia
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Sevilla, Spain, 41014
- Hospital Universitario Virgen Del Rocio
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Tarragona, Spain, 43007
- Hospital Universitari Joan Xxiii
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Terrassa, Spain, 08225
- Mutua de Terrassa
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Valencia, Spain, 46010
- Hospital Clínico Universitario de Valencia
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Valladolid, Spain, 41010
- Hospital Universitario Rio Hortega
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Barcelona
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Badalona, Barcelona, Spain, 08916
- Hospital Universitari Germans Trias i Pujol
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L'Hospitalet del Llobregat, Barcelona, Spain, 08907
- ICO Hospital Universitari de Bellvitge
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Coruña
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A Coruña, Coruña, Spain, 15006
- Hospital A Coruña
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Mallorca
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Palma de Mallorca, Mallorca, Spain, 07198
- Hospital Universitari Son Espases
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Palma de Mallorca, Mallorca, Spain
- Hospital Universitari Son Dureta
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Tarragona
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Tortosa, Tarragona, Spain, 43517
- Hospital Verge de la Cinta
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
OTHER: 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.
|
-Patients without favorable/intermediate characteristics.
Other Names:
-Patients with adverse prognosis with allogeneic peripheral blood stem cell (PBSC)tranplantation, CD34+ cell selection of the inoculum was performed.
Patients without favorable/intermediate characteristics and without matched related donor.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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2 months.
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Disease free survival (DFS).
Time Frame: 4 years.
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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. |
4 years.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Toxicity in patients over 60 years old.
Time Frame: 4 years.
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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.
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4 years.
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Evaluation of minimal residual disease (MRD) by flow cytometry and/or molecular markers during and after treatment.
Time Frame: 4 years.
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Study the immunophenotype characteristics and/or molecular markers at diagnosis, and during the different treatment phases.
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4 years.
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Feasibility of post-remission treatment in patients with 60 or more years old.
Time Frame: 4 years.
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Study the effect of post-remission treatments in patients with more than 60 years to evaluate the success of consolidation treatments.
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4 years.
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- AML-03
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