Periodic Reporting for period 1 - IntReALL 2020 (International Study for Treatment of Childhood Relapsed ALL 2020)
Período documentado: 2023-05-01 hasta 2024-10-31
Acute lymphoblastic leukaemia (ALL) is the most common cancer in children. While modern treatments cure over 90% of cases, ALL is still the leading cause of cancer-related deaths in children. The biggest risk factor for poor outcomes is relapse. The standard treatment is chemotherapy, which has serious side effects, both short-term and long-term. In case of relapse, children need even stronger treatments, such as high-dose chemotherapy and stem cell transplants, to achieve long-term cure. In recent years, new treatment options have been developed to target leukaemia cells more specifically while avoiding damage to healthy cells, thus reducing side effects. One group of these treatments are monoclonal antibodies, which target specific markers on leukaemia cells and help the immune system to destroy them. Another option is CAR T-cell therapy, where T-cells (a type of immune cell) are modified to recognize and attack leukaemia cells. This is especially effective for B-cell leukaemias (BCP-ALL), which express specific markers like CD19 and CD22. New small molecules are also being developed to target specific pathways activated in leukaemia cells, especially for T-cell leukaemias, which are harder to treat with immunotherapies.
The IntReALL consortium includes most European countries and is the largest research group focused on treating childhood relapsed ALL. The consortium conducts clinical trials to add new immunotherapy and targeted treatments into standard care, aiming to create more effective and less toxic treatments. We aim also at assuring equitable access to optimal therapy in every affected child regardless of ethnic origin, gender or socio-economic status in all participating countries. The group involves medical experts from 20 countries, pharmaceutical companies providing the drugs, scientific institutes offering the infrastructure for these large studies, and patient advocates to ensure the project is carried out in the best interest of patients and their families. The trials will also collaborate with regulatory authorities like the EMA to ensure they follow the law and may help extend the approval of new drugs. Ethical concerns, especially for such vulnerable patients, are carefully considered and approved by ethics committees.
The IntReALL consortium includes most European countries and is the largest research group focused on treating childhood relapsed ALL. The consortium conducts clinical trials to add new immunotherapy and targeted treatments into standard care, aiming to create more effective and less toxic treatments. We aim also at assuring equitable access to optimal therapy in every affected child regardless of ethnic origin, gender or socio-economic status in all participating countries. The group involves medical experts from 20 countries, pharmaceutical companies providing the drugs, scientific institutes offering the infrastructure for these large studies, and patient advocates to ensure the project is carried out in the best interest of patients and their families. The trials will also collaborate with regulatory authorities like the EMA to ensure they follow the law and may help extend the approval of new drugs. Ethical concerns, especially for such vulnerable patients, are carefully considered and approved by ethics committees.
The main goal of the project is a study in children with relapsed BCP ALL, stratified in different risk groups according to the delay of relapse after initial diagnosis, characteristics of the leukemia cells and affected body organs. For patients with standard risk relapse, at the beginning of therapy (induction), the immunotoxin inotuzumab ozogamicin will be compared with the usual chemotherapy. Following induction, the study was initially designed to compare blinatumomab (innovative immunotherapy) with chemotherapy, but other studies have already shown blinatumomab is more effective and causes fewer side effects. After ethical discussions, it was thus decided to treat all patients with blinatumomab, using historical data for comparison. Some high-risk patients will receive only one course of chemotherapy before blinatumomab and stem cell transplant. The trial is ready to start but needs final approval from the involved partners and regulatory authorities.
A statistical design and trial database have been created to meet all regulatory requirements, along with a registry for patients who cannot join the trial. An international board (FEDRRAL) has been set up to provide expert advice for patients with relapsed ALL, based on clinical and genetic data. This board has already completed a one-year pilot phase with 47 patients, showing that it works well.
The project also involves testing new anti-cancer targeted therapies in early-phase trials. A phase I/II trial for a new CAR T-cell treatment is being developed for patients with high-risk relapsed BCP ALL. Another trial will treat patients with early relapses after stem cell transplants using CAR T-cells from the donor. Additionally, a phase I/II trial is evaluating a CAR T-cell treatment for relapsed T-cell ALL. The consortium is also testing a new drug, venetoclax, in T-ALL patients along with chemotherapy. Close cooperation with the pharmaceutical industry, regulatory authorities, and patient advocates is ongoing to ensure all aspects of innovative drug development are properly considered.
A statistical design and trial database have been created to meet all regulatory requirements, along with a registry for patients who cannot join the trial. An international board (FEDRRAL) has been set up to provide expert advice for patients with relapsed ALL, based on clinical and genetic data. This board has already completed a one-year pilot phase with 47 patients, showing that it works well.
The project also involves testing new anti-cancer targeted therapies in early-phase trials. A phase I/II trial for a new CAR T-cell treatment is being developed for patients with high-risk relapsed BCP ALL. Another trial will treat patients with early relapses after stem cell transplants using CAR T-cells from the donor. Additionally, a phase I/II trial is evaluating a CAR T-cell treatment for relapsed T-cell ALL. The consortium is also testing a new drug, venetoclax, in T-ALL patients along with chemotherapy. Close cooperation with the pharmaceutical industry, regulatory authorities, and patient advocates is ongoing to ensure all aspects of innovative drug development are properly considered.
The results of this project will improve survival rates for children with relapsed ALL and reduce the side effects of treatment. The main trial, IntReALL BCP 2020, and the early-phase trials will create new treatment strategies that go beyond what is currently available. The results will become the standard treatment in participating countries, and hopefully in others around the world in the future. The innovative trial infrastructure will be used in future studies. The FEDRRAL board sets a new standard for expert advice, helping to reduce inequalities in leukaemia treatment in Europe, and could be used as a model in other parts of the world. A key innovation is the development of academic centres in Europe that can produce CAR T-cells, making this treatment more flexible and driven by research.