Biology and Treatment Strategy of AML in Its Subgroups: Multicenter Randomized Trial by the German Acute Myeloid Leukemia Cooperative Group (AMLCG)

Study Overview
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Brief Summary
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The study in patients with primary and secondary AML and high-risk MDS uses a risk-stratified, randomized design to evaluate the role of high-dose araC in induction, of G-CSF priming, and of autologous stem cell transplantation.

Detailed Description
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The present study by the German AML Cooperative Group has been designed in order to investigate the effects of AML typical therapeutic strategies for AML and related diseases. Thus, the entry criteria are age starting from 16 years with no upper age limit, de novo AML or AML secondary to chemotherapy or radiotherapy of another disease or myelodysplasia subtype RAEB with bone marrow blasts greater than 10 %. All randomization is stratified according to karyotype favorable / intermediate / unfavorable. Additional stratification is according to LDH </>= 700 U and age </>= 60 Y. Standard treatment is (A) double induction with TAD and HAM, consolidation with TAD and maintenance treatment with monthly AD-AT-AC-AT -, rotatingly. Experimental modifications to be compared with stan-dard treatment are (B) double induction with HAM-HAM, (C) multiple course G-CSF before and during chemotherapy courses and (D) instead of maintenance treatment myeloablative consolidation with Bu/Cy and autologous blood stem cell transplantation. Intent to treat conditions are guaranteed by randomization before induction treatment starts. In order to evaluate the effect of every single modification randomization to (C) is equally distributed to the patients in treatment arms (A) and (B) which is also true for the randomization to (D) (balanced randomization). Similarly balanced between treatment arms are the patients according to diagnosis, age and risk factors like serum LDH and karyotype. In order to adapt treatment intensity to age patients of 60 years and older receive the second induction course only in case of 5 % or more residual bone marrow blasts. In addition, the AraC dose in HAM is reduced to 1 instead of 3 g/sqm in this age group. Furthermore, there is no treatment arm including stem cell transplantation in patients of 60+ years. Pri-mary endpoint to compare the therapeutic strategies is event-free survival from treatment start (A, B, C) and from achievement of remission (D), respectively. By this design the AMLCG 2000 trial can contribute relevant experiences on optimum therapeutic strategies for the biological subgroups of de novo AML, secondary AML and MDS. Furthermore, new biological subgroups and their significance related to treatment strategies can be defined.

Official Title
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Risk-stratified Therapy for Primary and Secondary AML and MDS. A Randomized Study by AMLCG in Relation to Cytogenetically Defined Prognostic Factors (1) on the Role of High-dose AraC as Part of Double Induction, (2) on G-CSF Priming, and (3) on High-dose Chemotherapy With Stem Cell Transplantation

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Cytarabine
* Drug: Thioguanine
* Drug: Daunorubicin
* Drug: Cyclophosphamide
* Drug: G-CSF
* Procedure: Autologous stem cell transplantation
* Procedure: Allogeneic stem cell transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute myeloid leukemia (de-novo AML, secondary AML, high-risk MDS) Age 16 - no upper age limit Written informed consent Exclusion Criteria: Severe comorbidity Presence of other malignancy Prior anti-leukemic treatment Pregnancy Severe psychiatric disorder or other circumstances which may compromise cooperation of the patients

Ages Eligible for Study
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Minimum Age: 16 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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Cytarabine|see protocol|
|Drug: Thioguanine|see protocol|
|Drug: Daunorubicin|see protocol|
|Drug: Cyclophosphamide|see protocol|
|Drug: G-CSF|see protocol|
|Procedure: Autologous stem cell transplantation|for details see protocol|
|Procedure: Allogeneic stem cell transplantation|for details see protocol|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission rate, Remission duration,Relapse-free survival, Overall survival, Event-free survival |  | 12-18months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time and dose compliance, Realisation of SCT, Toxicity according to WHO |  | 12-18months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML treatment, de-novo, secondary, high-risk MDS, chemotherapy, autologous SCT, adult