Description:
Advances in the biological characterization of AML can now make a proper estimate of the risk
of recurrence and likelihood of survival of different groups of patients according to the
expression of different disease parameters. Karyotype, the molecular alterations affecting
genes FLT3, NPM1 and CEBPA, minimal residual disease by flow cytometry and response to first
induction cycle are variables that must be taken into consideration when planning the
treatment of first line from a patient with AML.
This breakthrough in the field of biology has not resulted yet in the development of new
drugs really effective in the treatment of AML. Therefore, the core of the treatment continue
to rely on the use of traditional chemotherapy combined or not with allogeneic hematopoietic
stem cell. Both treatments differ in their antileukemic efficacy, higher in aloTPH, as well
as their toxicity and procedure-related mortality, increased also in the aloTPH. These
aspects should be added that most candidates aloTPH patients lack an HLA identical sibling
donor forcing the search for alternative sources and hematopoietic stem cell donors. These
transplants alternative, but are not committed to their antileukemic efficacy, it does have
implied a greater toxicity. Therefore, the ultimate effectiveness of these procedures depends
largely on the proper selection of candidates for the same.
While there is broad agreement in terms of induction chemotherapy using a combination of
cytarabine with anthracycline, the choice of chemotherapy regimen is controversial
postremisión today. In the poor prognosis of itself involve the LMA, patients classified as
"favorable group" are acceptable disease-free survival with consolidation schemes involving
high-dose cytarabine. For other patients appear to be inappropriate to combine cytarabine
with an anthracycline, at least one cycle of consolidation, and raise the option of
allogeneic different depending on prognostic markers
Title
- Brief Title: PETHEMA-LMA10: Treatment of Acute Myeloblastic Leukemia (AML) in Patients Less Than or Equal to 65 Years
- Official Title: PROTOCOL FOR First Line TREATMENT ADAPTED TO RISK of Acute Myeloblastic Leukemia in Patients LESS THAN OR EQUAL TO 65 YEARS
Clinical Trial IDs
- ORG STUDY ID:
PETHEMA-LMA10
- NCT ID:
NCT01296178
Conditions
- Acute Myeloblastic Leukemia
Interventions
| Drug | Synonyms | Arms |
|---|
| IDARUBICINE | | |
| ARA-C | | |
Purpose
Advances in the biological characterization of AML can now make a proper estimate of the risk
of recurrence and likelihood of survival of different groups of patients according to the
expression of different disease parameters. Karyotype, the molecular alterations affecting
genes FLT3, NPM1 and CEBPA, minimal residual disease by flow cytometry and response to first
induction cycle are variables that must be taken into consideration when planning the
treatment of first line from a patient with AML.
This breakthrough in the field of biology has not resulted yet in the development of new
drugs really effective in the treatment of AML. Therefore, the core of the treatment continue
to rely on the use of traditional chemotherapy combined or not with allogeneic hematopoietic
stem cell. Both treatments differ in their antileukemic efficacy, higher in aloTPH, as well
as their toxicity and procedure-related mortality, increased also in the aloTPH. These
aspects should be added that most candidates aloTPH patients lack an HLA identical sibling
donor forcing the search for alternative sources and hematopoietic stem cell donors. These
transplants alternative, but are not committed to their antileukemic efficacy, it does have
implied a greater toxicity. Therefore, the ultimate effectiveness of these procedures depends
largely on the proper selection of candidates for the same.
While there is broad agreement in terms of induction chemotherapy using a combination of
cytarabine with anthracycline, the choice of chemotherapy regimen is controversial
postremisión today. In the poor prognosis of itself involve the LMA, patients classified as
"favorable group" are acceptable disease-free survival with consolidation schemes involving
high-dose cytarabine. For other patients appear to be inappropriate to combine cytarabine
with an anthracycline, at least one cycle of consolidation, and raise the option of
allogeneic different depending on prognostic markers
Detailed Description
Primary objectives
1. Optimizing current treatment of AML based on the classification of patients into
different risk groups according to parameters cytogenetic and molecular response to
treatment and to analyze its effectiveness in terms of survival.
2. Apply a uniform treatment to individual patients according to previously defined
prognostic groups.
Secondary Objectives
1. Correlate the different clinical and biological characteristics with response rates and
patient outcomes.
2. Studying the role of minimal residual disease by molecular techniques in anticipation of
relapse of AML
Trial Arms
| Name | Type | Description | Interventions |
|---|
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of AML according to WHO criteria
- Previously untreated AML, including AML de novo,AML secondary to MDS or previous
chemotherapy or radiotherapy
- No promyelocytic leukemia (no t (15, 17) or PML-RARa rearrangement and its variants)
- Age ≤ 65 years
- ECOG performance status 0-2
- Provide written informed consent
- Being able to comply with protocol procedures
- Not to be fertile or willing to use a method of birth control during treatment and
until the end of it
- Adequate renal and hepatic function as follows, provided the changes, which would be
not due to the disease: Total bilirubin < 1.5 x upper limit of normal (ULN)
institutional and AST and ALT < 2.5 x ULN, and Serum creatinine < 2.5 mg / dL.
- Adequate cardiac function determined by at least 1 of the following:
Left ventricular ejection fraction (LVEF) > 40% measured by echocardiography in multiport
scanner acquisition (MUGA) or isotope angiography, or Left ventricular fractional
shortening > 22% measured in echocardiography
Exclusion Criteria:
- LPA diagnosis according to WHO criteria
- Previously untreated AML, except for the administration of hydroxyurea as a
cytoreductive agent which itself is permitted
- AML secondary to chronic myeloproliferative syndrome
- Age> 65 years
- ECOG performance status> 2
- Absence of written informed consent
- Being unable to comply with protocol procedures
- Be fertile and not willing to use a method of birth control during treatment and until
the end of it
- Hypersensitivity to any drug protocol
- Positive for HIV
- Abnormal liver and renal functions as indicated below, provided the changes, which
would be not due to the disease: Total bilirubin> 1.5 x upper limit of normal (ULN)
institutional and AST and ALT> 2.5 x ULN, and serum creatinine> 2.5 mg / dL
- Altered cardiac function determined by at least 1 of the following:
Left ventricular ejection fraction (LVEF) <40% measured by echocardiography in multiport
scanner acquisition (MUGA) or isotope angiography, or Left ventricular fractional
shortening <22% measured by echocardiography
| Maximum Eligible Age: | 65 Years |
| Minimum Eligible Age: | N/A |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Number of survival months in treated AML patients less or equal to 65 years as a measure of survival time |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | Optimizing current treatment of AML based on the classification of patients into different risk groups according to parameters cytogenetic and molecular response to treatment and to analyze its effectiveness in terms of survival |
Secondary Outcome Measures
| Measure: | Response rates |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | Correlate the different clinical and biological characteristics with response rates and patient outcomes |
| Measure: | Determinate the minimal residual disease |
| Time Frame: | 2 years |
| Safety Issue: | |
| Description: | Studying the role of minimal residual disease by molecular techniques in anticipation of relapse of AML |
Details
| Phase: | N/A |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | PETHEMA Foundation |
Last Updated
March 23, 2021
