Clinical trial NCT00266136: Biology and Treatment Strategy of AML in Its Subgroups: Multicenter Randomized Trial by the German Acute Myeloid Leukemia Cooperative Group (AMLCG)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Myeloid Leukemia
Keywords: AML treatment, de-novo, secondary, high-risk MDS, chemotherapy, autologous SCT, adult
Lead sponsor: University Hospital Muenster
Sponsor class: OTHER
Collaborators: name: Deutsche Krebshilfe e.V., Bonn (Germany)
name: German Federal Ministry of Education and Research
First posted: 2005-12-15
Enrollment: 3500
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Remission rate, Remission duration,Relapse-free survival, Overall survival, Event-free survival
timeFrame: 12-18months
Secondary outcomes:
measure: Time and dose compliance, Realisation of SCT, Toxicity according to WHO
timeFrame: 12-18months
Other outcomes:
Locations:
city: Muenster
country: Germany
facility: University of Muenster, Medical Center, Department of Medicine, Hematology and Oncology
Study officials:
affiliation: University of Muenster, Medical Center, Department of Medicine, Hematology and Oncology
name: Thomas Buechner, MD PhD
role: STUDY_CHAIR
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