Getting Targeted Therapies to Pediatric Patients: The iLTB and the Pinocchio Study GETTING TARGETED THERAPIES TO PEDIATRIC PATIENTS: THE ILTB AND THE PINOCCHIO STUDY

Abstract

Molecular profiling is becoming standard of care in pediatric oncology, leading to an increase in knowledge about genetic aberrations at the basis of cancer development and subsequently to an increase of Targeted Therapies. Interesting novel therapies include the Tyrosine Kinase Inhibitors, Monoclonal antibodies, CAR-T cell therapies, and NK cell therapies. Approval for the usage of these novel targeted therapies in pediatric patients is lagging adult approval by a significant margin of 6 years. For this reason novel clinical trial designs in the form of master protocols are under development: to accelerate clinical trials in small subsets of pediatric patients. At the basis of a master protocol a profiling initiative molecularly profiles the patients and recommends enrolment into a specific clinical trial or a specific arm of a master protocol. The International Leukemia Target Board (iLTB) is an European tumor board aiming to enroll all patients with a r/r hematological malignancy and no standard of care treatment option in Europe. After inclusion and discussion the iLTB recommends treating physicians the fitting clinical trials or therapies for their pediatric patient. For a molecular profiling initiative to work efficiently, a rigid framework to enroll the patient and store all their data is necessary. For this reason, iLTB database was designed and created. Several improvements on a standard clinical trial database design were thought up, considered, designed, and implemented to ensure a couple of core conditions: Easy enrolment of patients from anywhere in Europe, smooth data import and export, and, as a result, accelerating trial enrolment in small pediatric clinical trials. Because of the absence of enough safety and efficacy data of targeted therapies in pediatric patients, targeted therapies are often not prescribed to them. In order to enlarge the current knowledge about the pharmacokinetics of targeted therapies in pediatric patients, the Pinocchio protocol was amended to also include Tyrosine Kinase Inhibitors. The study design, study outcomes, informed consent forms and database were designed and written, and the protocol was submitted to the Medical Ethics Committee receiving conditional approval. As soon as final approval is granted, patient enrolment into Pinocchio Stratum 2 can start.