Information about Project 5: Acute myeloid leukemia (AML)
Objectives
This network aims at integrating the acquired cross disciplinary input from high quality AML trials as well as from new molecular knowledge in order to translate them into an improvement in patients treatment. To perform this on an European platform requires a network of AML trials to harmonize protocol standards, adopt new therapists and trial groups and spread excellence through communication and education. Using the European AML Network, through collaboration with WP12 molecular methods can be standardized and used for monitoring MRD with the aim to further validate and optimize therapeutic strategies based upon molecular MRD.
The objectives of a joint research program in the European AML Network are (1) finding a consensus on cooperation between AML trial groups by (2) adopting of common protocol standards including (3) entry criteria and patient selection, (4) establishing networking instruments such as a general upfront randomization and (5) a common standard treatment arm. (6) Cross trial comparison and validation of treatment strategies provided by the network structure. (7) Refining the monitoring of antileukemic effects on the basis of molecular MRD. (8) Using the European AML Network as an instrument to accelerate the therapeutic progress against AML.
Description of work
The basic structure of the European AML Network is formed by the AML trial groups, their integration, joint research, spreading excellence, expanding their responsibilities, and sharing governance. Other links will be a common data set and a cytogenetic/molecular genetic data base. Main carrying elements are the existing qualified trial groups, national like MRC, GIMEMA, PETHEMA, HOVON, GOELAM, national as a cooperation of trial groups like German AML Intergroup, and international like EORTC. These groups offer participation in their trials to single centers or entire groups. They equally invite new groups as participants in the network. This strategy aims at improving the quality of patients care and cure from AML across Europe and beyond.
Therefore, spreading excellence by exchange of experience, education and training is a primary objective of the AML Network. The educational program has to consider the skills in up-to-date diagnostics and classification, prognosis and differential treatment indication, estimation of therapeutic risk, administration of antileukemic and supportive treatment, patients monitoring and documentation, as well as the methodology of clinical trials like decision about eligibility, protocol adherence, patient informed consent, randomization, assessment of outcomes, documentation, evaluation, reporting standards and publication. Measures to communicate these knowledges and skills are practical training of trainee doctors and nurses at qualified centers, diagnostic courses on cytomorphology, immunophenotyping, basic cytogenetics and molecular knowledge, diagnostic slide sets and guidelines by the AML Network as well as state-of-the-art lectures by opinion leaders.
Since there is a continuous increase in the molecular and biological understanding of AML, the disease classification, diagnostic and therapeutic standards are subject to periodic revision. This process also requires revisions of trial protocols which may lead to differences within Europe. In order to spread excellence of uniform quality by the AML Network it is necessary to adopt up-to-date common protocol standards as defined by the EU and by the NCI initiated working party.
Harmonizing standards is also a minimum requirement for joint research activities among the trial groups in the AML Network. Thus, comparisons of treatments across the trials requires agreements on patient selection; thereby attempting to avoid differences due to inter-trial variations in entry criteria, or during the course of treatment by dropouts due to non-qualification for randomizations in remission. Differences in patient selection, however, are responsible for incomparabilities of outcomes. Networking instruments to improve comparability will be uniform entry criteria, and randomization taking place before the start of treatment so that patients become defined, definitely registered and their outcome evaluable and comparable according to intent-to-treat. A further harmonization of patient comparability will be the implementation of a common standard treatment arm to be worked out by the European AML Network.
The above networking instruments will allow cross trial treatment comparisons and may thus accelerate therapeutic progress. Furthermore, effective evaluation of new drugs using the Network can be provided.
In addition to a joint research program on cross trial treatment optimization, the AML Network by its design will provide a solid basis for treatment research in the light of new molecular knowledge i.e. by monitoring MRD using disease specific cell markers. These will include the AML typical fusion genes PML/RARa, AML1/ETO, CBFb/MYH11, and mutations of the Flt3- and MLL genes. In cases lacking these molecular markers aberrant immunophenotypes of leukemic blasts will contribute to MRD monitoring.