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

University Hospital Muenster

Status and phase

Completed

Phase 3

Conditions

Acute Myeloid Leukemia

Treatments

Drug: G-CSF

Procedure: Allogeneic stem cell transplantation

Drug: Thioguanine

Procedure: Autologous stem cell transplantation

Drug: Cyclophosphamide

Drug: Daunorubicin

Drug: Cytarabine

Study type

Interventional

Funder types

Other

Identifiers

NCT00266136

AMLCG 99

BMBF 01 GI 02070

Details and patient eligibility

About

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.

Full 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.

Enrollment

3,500 patients

Sex

All

Ages

16+ years old

Volunteers

No 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