Risk Adapted Treatment for Primary Acute Myeloid Leukemia (AML)

NCT ID: NCT01723657

Last Updated: 2012-11-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

862 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-10-31

Study Completion Date

2012-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Leukemia, Myelocytic, Acute

Keywords

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Leukemia Myeloid Acute Young CETLAM

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type OTHER

Ara-C

Intervention Type DRUG

* Intermediate dose during induction phase to remission.
* High dose during consolidation phase in patients with favorable cytogenetics and leukocyte index below 20.

Autologous peripheral blood stem cell transplantation.

Intervention Type OTHER

* In patients with favorable cytogenetics with a Leukocyte index above 20.
* Patients with normal karyotype, and one cycle of chemotherapy to achieve complete remission, without adverse molecular and/or minimal residual disease (MRD) characteristics, regardless availability of a matched donor.

Allogeneic matched related or unrelated donor transplant.

Intervention Type OTHER

-Patients without favorable/intermediate characteristics.

G-CSF

Intervention Type DRUG

* Administration at induction phase to remission, days 0 to 7. G-CSF will not be initiated if the leukocyte count is over 30x10e9/L at diagnosis or will be interrupted if the leukocyte count during treatmen arises 30x10e9/L.
* Administration at consolidation phase, days 4 to 6 (3 doses). G-CSF will be interrupted if the leukocyte count during treatment arises 30x10e9/L.

CD34+ selection.

Intervention Type OTHER

-Patients with adverse prognosis with allogeneic peripheral blood stem cell (PBSC)tranplantation, CD34+ cell selection of the inoculum was performed.

Mylotarg purging before autologous PBSC transplantation

Intervention Type OTHER

Patients without favorable/intermediate characteristics and without matched related donor.

Interventions

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Ara-C

* Intermediate dose during induction phase to remission.
* High dose during consolidation phase in patients with favorable cytogenetics and leukocyte index below 20.

Intervention Type DRUG

Autologous peripheral blood stem cell transplantation.

* In patients with favorable cytogenetics with a Leukocyte index above 20.
* Patients with normal karyotype, and one cycle of chemotherapy to achieve complete remission, without adverse molecular and/or minimal residual disease (MRD) characteristics, regardless availability of a matched donor.

Intervention Type OTHER

Allogeneic matched related or unrelated donor transplant.

-Patients without favorable/intermediate characteristics.

Intervention Type OTHER

G-CSF

* Administration at induction phase to remission, days 0 to 7. G-CSF will not be initiated if the leukocyte count is over 30x10e9/L at diagnosis or will be interrupted if the leukocyte count during treatmen arises 30x10e9/L.
* Administration at consolidation phase, days 4 to 6 (3 doses). G-CSF will be interrupted if the leukocyte count during treatment arises 30x10e9/L.

Intervention Type DRUG

CD34+ selection.

-Patients with adverse prognosis with allogeneic peripheral blood stem cell (PBSC)tranplantation, CD34+ cell selection of the inoculum was performed.

Intervention Type OTHER

Mylotarg purging before autologous PBSC transplantation

Patients without favorable/intermediate characteristics and without matched related donor.

Intervention Type OTHER

Other Intervention Names

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Filgastrim.

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jorge Sierra, MD

Role: PRINCIPAL_INVESTIGATOR

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Salut Brunet, MD

Role: STUDY_CHAIR

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Locations

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Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, Spain

Site Status

Hospital del Mar

Barcelona, Barcelona, Spain

Site Status

Centro Medico Teknon

Barcelona, Barcelona, Spain

Site Status

Hospital de la Santa Creu i Sant Pau

Barcelona, Barcelona, Spain

Site Status

Hospital Vall d'Hebron

Barcelona, Barcelona, Spain

Site Status

Hospital Clínic de Barcelona

Barcelona, Barcelona, Spain

Site Status

ICO Hospital Universitari de Bellvitge

L'Hospitalet Del Llobregat, Barcelona, Spain

Site Status

Hospital A Coruña

A Coruña, Coruña, Spain

Site Status

Hopital Universitari de Girona Dr. Josep Trueta

Girona, Girona, Spain

Site Status

Hospital Universitari Arnau de Vilanova

Lleida, Lleida, Spain

Site Status

Hospital Universitario La Paz

Madrid, Madrid, Spain

Site Status

Hospital Universitario Virgen de la Victoria

Málaga, Malaga, Spain

Site Status

Hospital Universitari Son Espases

Palma de Mallorca, Mallorca, Spain

Site Status

Hospital Universitari Son Dureta

Palma de Mallorca, Mallorca, Spain

Site Status

Hospital General Universitario de Murcia

Murcia, Murcia, Spain

Site Status

Hospital Universitario Virgen del Rocio

Seville, Sevilla, Spain

Site Status

Hospital Universitari Joan XXIII

Tarragona, Tarragona, Spain

Site Status

Hospital Verge de la Cinta

Tortosa, Tarragona, Spain

Site Status

Mutua de Terrassa

Terrassa, Terrassa, Spain

Site Status

Hospital Clinico Universitario de Valencia

Valencia, Valencia, Spain

Site Status

Hospital Universitario Rio Hortega

Valladolid, Valladolid, Spain

Site Status

Countries

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Spain

Other Identifiers

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AML-03

Identifier Type: -

Identifier Source: org_study_id