INTREALL

"International study for treatment of childhood relapsed ALL 2010 with standard therapy, systematic integration of new agents, and establishment of standardized diagnostic and research"

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 Obiettivo del progetto (Objective)

'Though survival of children with acute lymphoblastic leukaemia (ALL) has improved, relapse remains a leading cause of mortality in childhood cancer. Given the rarity of the disease, only a large international cooperative group can recruit sufficient patients for prospective studies with specific questions in biologic subgroups. Under the umbrella of the I-BFM SG all relevant mainly European study groups are creating the worldwide largest Study for Children with Relapsed ALL (IntReALL 2010). The aim is to develop optimized standard treatment as platform for systematic randomized phase II and III studies on the most promising new and targeted agents. An adequate trial structure, an optimized web based database, and standardized diagnostic methods need to be established. Patients are stratified into a standard (SR) and a high risk (HR) group according to established factors. For SR patients, the best available treatment protocols ALL-REZ BFM 2002 and ALL R3 are randomly compared, and the additional effect on survival of the humanized monoclonal CD22 directed antibody epratuzumab is investigated. HR patients who have unsatisfying remission rates will receive an intensified induction with the new nucleoside analogue clofarabine compared to standard induction therapy. IntReALL 2010 allows for comprehensive tumour banking and systematic biologic research in subgroups with correlation to clinical outcome. SMEs will be involved into project management, data base development, and pharmaceutical and biotechnological research to ensure innovation in the respective areas. IntReALL 2010 is embedded in a network of European academic structures relevant for childhood cancer. It will be a cornerstone of drug development in childhood leukaemia and the only trial with the potential for well powered phase III studies in this indication. IntReALL 2010 will harmonize ALL-relapse therapy, establish highest diagnostic and therapeutic standard and improve survival of children with ALL.'

Introduzione (Teaser)

Acute lymphoblastic leukaemia (ALL) is a malignant cancer characterised by over-production of white blood cells that predominantly affects children, with fatal relapse in some patients. An EU-funded project is investigating novel therapies for ALL.

Descrizione progetto (Article)

Relapse of ALL is currently treated with intensive chemotherapy and haematopoietic stem cell transplantation (HSCT), and over the decades, survival prognosis has improved. New drugs that are potentially more beneficial with fewer toxic side-effects need to be tested prior to licensing approval for commercial application. However, incidence of relapsed ALL cases are too few and international collaboration is needed for a successful clinical trial and accurate data analysis.

The EU-funded http://www.intreall-fp7.eu (INTREALL) project is comprised of several European and international study groups with expertise in childhood cancers. INTREALL will facilitate an international clinical trial on childhood relapsed ALL with global collaboration between hospitals and innovative small and medium-sized enterprises (SMEs). Efforts will be made to optimise treatment strategies by investigating standard as well as innovative therapies in compliance with good clinical practices (GCPs).

Consortium members laid the groundwork for implementation of the clinical trial INTREALL 2010 to investigate ALL relapse in children. Treatment strategies will be based on risk stratification of patients into standard-risk (SR) and high-risk (HR) categories. Requisite protocols, statistical plans, approvals, databases and infrastructural setups are in progress for the SR and HR groups of clinical trials.

For SR patients, the two most successful treatment protocols in practice will be compared. Some SR patients will also be treated with Epratuzumab, a humanised monoclonal antibody that binds to glycoprotein CD22 on cancerous cells. A treatment course of clofarabine combined with cyclophosphamide or etoposide will be tested on HR patients.

For the assessment of treatment outcomes, diagnostic procedures were standardised along with quality control strategies. Test protocols for studying disease pathogenesis, new risk factors and targets for new drugs were also set up along with a virtual tissue bank. Pilot studies established the sensitivity and specificity of pooling technology for deep sequencing of candidate genes.

INTREALL initiatives will provide comprehensive data on ALL. Results will serve as a reference for determining treatment strategies and monitoring patient progress as well as for future ALL clinical trials. Due to the rareness of ALL, clinical trials will provide unprecedented opportunities to test the efficacy of promising new drugs such as Epratuzumab. Project outcomes could reveal novel treatment options that could personalise care for ALL patients to improve prognosis and quality of life.