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

Sponsor

University Hospital Muenster (Other)

Overall Status

Completed

CT.gov ID

NCT00266136

Collaborator

Deutsche Krebshilfe e.V., Bonn (Germany) (Other), German Federal Ministry of Education and Research (Other)

3,500

Enrollment

Location

160

Duration (Months)

21.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Cytarabine Drug: Thioguanine Drug: Daunorubicin Drug: Cyclophosphamide Drug: G-CSF Procedure: Autologous stem cell transplantation Procedure: Allogeneic stem cell transplantation	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

3500 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jun 1, 1999

Actual Primary Completion Date :

Jan 1, 2007

Actual Study Completion Date :

Oct 1, 2012

Outcome Measures

Primary Outcome Measures

Remission rate, Remission duration,Relapse-free survival, Overall survival, Event-free survival [12-18months]

Secondary Outcome Measures

Time and dose compliance, Realisation of SCT, Toxicity according to WHO [12-18months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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