Boosting new therapies for relapsed ALL patients
Survival rates for ALL may have jumped from less than 20 % to over 80 % over the past 40 years, but it all comes at a price. Treatments are now longer and more toxic, and 50 % of the patients who relapse still die in the face of failing combinations of chemotherapy and haematopoietic stem cell transplantation (HSCT). Noting the existence of new and promising drugs waiting to be tested on patients, the INTREALL (International study for treatment of childhood relapsed ALL 2010 with standard therapy, systematic integration of new agents, and establishment of standardised diagnostic and research) project has set out to build the largest clinical trial platform for diagnostics and treatment of childhood relapsed ALL. ‘By optimising the standard of care diagnostics and treatment and investigating the integration of new targeted drugs, we aim at improving survival rates and reducing toxicity. This is being done on an international level providing a benefit for all European citizens,’ says Dr von Stackelberg, coordinator of the project. One of INTREALL’s most important objectives was the implementation of Phase 2 and 3 clinical trials that could serve as references for the whole world, also providing a unique platform for drug development. Separate trials for standard risk (SR) and high risk (HR) childhood relapsed ALL have been developed, and the project is notably helping investigate the use of Epratuzumab — a CD22 directed monoclonal antibody developed by project partner Immunomedics, which is currently undergoing a large, randomised Phase 3 trial. ‘INTREALL allows for the conducting of prospective randomised trials in a reasonable time frame and in the best interest of the patients,’ Dr von Stackelberg explains. ‘By doing this, it allows for investigating the safety and efficacy of new targeted therapies in context with standard curative treatment strategies.’ Besides Epratuzumab, a notable success in this regard was the integration of a decisive Phase 3 trial on Blinatumomab into the treatment strategy for high-risk patients. To make clinical trial results available, the consortium has developed a study database for both SR and HR trials, using a system called MARVIN that was developed by project partner XClinical. From there, patients not included in the trials due to clinical or organisational reasons can access a registry tool directing them to open clinical trials and to biologic studies. Other project-enabled tools include standardised diagnostic procedures, reference laboratories and a virtual tissue bank for patient material that have been established in all participating countries. The platform can also be used for future trials. In fact, Dr von Stackelberg and his team expect the project to keep going beyond its foreseen completion in September 2017, with support from national funding resources. ‘The diagnostic and therapeutic platform will be available for more interested European and non-European countries and study groups. A series of the most attractive and effective new agents will be investigated within the INTREALL group, which will continue to exist in interaction with the competent authorities and industry.’ If the consortium successfully achieves all its objectives, Dr von Stackelberg expects survival rates to improve by about 15 %.
Keywords
INTREALL, acute lymphoblastic leukaemia, ALL, therapies, clinical trial, relapse, epratuzumab, Immunomedics, Blinatumomab, database, diagnostic
