Treatment of Adults Aged Up to 60 Years With De Novo Acute Myeloblastic Leukaemia,Secondary AML, or RAEB-T

Study Overview
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Brief Summary
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This randomized phase II/III trial investigates the antileukemic activity and toxicity of the FLAG-Ida regimen as a second induction course in patients with acute myeloid leukaemia and bad response to the first induction cycle and/or with a high risk karyotype and compares the antileukemic activity and toxicity of high dose cytarabine/daunorubicin vs. autologous peripheral blood stem cell transplantation as late consolidation therapy in standard risk patients.

Detailed Description
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Assessment of the antileukemic activity and toxicity of the FLAG-Ida regimen as a second induction course in patients with bad response to the first induction cycle and/or with a high risk karyotype. Optimization of the late consolidation therapy in standard risk patients (SR) by a prospective randomized trial comparing a high-dose cytarabine/daunorubicin (HD-Ara-C/DNR) based late consolidation therapy with an autologous peripheral blood stem cell transplantation (PBSCT) Assessment of the antileukemic activity of the different treatment elements by monitoring residual disease (MRD) after induction, early and late consolidation by Real-time PCR Assessment of the prognostic relevance of minimal residual disease by quantification of the residual leukemic burden in haematological remission by Real-time PCR during follow-up

Official Title
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Protocol for the Treatment of Adults Aged </= 60 Years With De Novo Acute Myeloblastic Leukaemia or Secondary AML or RAEB-T (AML 01/99 Trial)

Conditions
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De Novo Akute Myeloid Leukemia (AML), Secondary Acute Myeloid Leukemia (AML), Refractory Anemia With Excess of Blasts in Transformation

Intervention / Treatment
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* Drug: Cytarabine
* Drug: Idarubicin
* Drug: Etoposide
* Drug: Fludarabine
* Drug: G-CSF
* Drug: Daunorubicine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of de-novo AML, FAB M 1, 2, 4 - 7 diagnosis of secondary AML after chemo-/radiotherapy or MDS diagnosis of RAEB-T age between 16 and 60 years (including 60 years) women after exclusion of pregnancy written informed consent Exclusion Criteria: patients with severe disease of the heart (e.g. cardial failure NYHA III/IV; history of myocardial infarction within the last 6 months;severe ventricular arrythmias (Lown III to IV) patients with DLCO < 50% patients with creatinine clearance < 60 ml/min patients with bilirubin > 2mg% (34.2 mmol/L) patients with severe complications of the leukaemia such as uncontrolled bleeding, pneumonia with hypoxia or shock patients with a psychiatric, addictive, or any disorder which compromises ability to give truly informed consent for participating in this study HIV positivity patients with a t(15;17) translocation

Ages Eligible for Study
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Minimum Age: 16 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Cytarabine|nan|
|Drug: Idarubicin|nan|
|Drug: Etoposide|nan|
|Drug: Fludarabine|nan|
|Drug: G-CSF|nan|
|Drug: Daunorubicine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy and toxicity of FLAG-Ida as second induction course in high risk patients. |  |  | 
| Efficacy and toxicity of high-dose cytarabin/daunorubicin (HD-Ara-C/DNR) based late consolidation therapy vs. autologous peripheral blood stem cell transplantation in standard risk patients. |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monitoring residual disease (MRD) after induction, early and late consolidation by Real-time PCR. |  |  | 
| Assessment of the prognostic relevance of minimal residual disease by quantification of minimal residual disease. |  |  |