SUMMARY
This project has been designed to offer an opportunity to children with acute leukaemia who cannot receive a bone marrow transplant because the cancer is in a dangerous state. The joint use of rescue chemotherapy and immunotherapy allows the children to overcome this, and improve to a point that the bone marrow transplant, and therefore the cure, is possible.
DEVELOPMENT OF THE PROJECT
Every year, 1,200 children are diagnosed with cancer in Spain, of which 300 pass away. It is the leading cause of childhood death in our country.
The project is named after Lydia, a 6-year-old girl who sadly did not survive her cancer. Her parents wanted to donate all the funds they collected to pay for new treatments overseas so that other children can have the opportunity that Lydia could not have.
The aim is to improve children’s immune system and slow down leukaemia with cell therapy (with NK cells) and “rescue chemo” so that they can be in a condition to receive a bone marrow transplant.
JUSTIFICATION
We propose a clinical trial whose aim is to determine the safety and effectiveness of the infusion of activated and expanded Natural Killer cells (NKAE) from a haploidentical donor, together with rescue chemotherapy, in children, adolescents and young adults with refractory acute leukaemia (AL). AL is the most common cancer in the paediatric population and, even though at the present time cure rates are high, AL relapses and refractoriness to chemotherapy still pose a serious clinical problem. Rescue chemotherapy in refractoriness or relapse achieves suboptimal clinical remissions, which could be improved with the help of cell therapy.
Recent advances in immunological knowledge about leukaemia and biotechnological development allow us to create and develop new immunotherapy strategies in very unfavourable clinical situations. In this sense, Natural Killer (NK) cell treatment constitutes a developing new cell therapy. NK cells are lymphocytes of the innate immune system whose main function is the defence against tumour development.
This property is regulated by a complex recognition system between receptors, activators and inhibitors of the NK cells with their ligands in the tumour cells. Most leukaemia cells express ligands for NK receptors, however, the patient’s immune system is incapable of giving an effective anti-tumour response.
At present, we can obtain NK cells from the peripheral blood of healthy donors by means of a cell co-culture process between the donor’s mononuclear cells and the K562 cell line. This is done on a large scale and for clinical use in humans.
OBJECTIVES
This is an open, non-randomised, multicentric exploratory therapeutic study (according to the terminology of the “ICH Harmonised Tripartite Guideline Topic E8. General Considerations for Clinical Trials”. EMEA, March 1998. CPMP/ICH/291/95). It is considered Phase I/II, as it studies the safety and effectiveness of the infusion of haploidentical, allogenic, differentiated adult NK cells from peripheral blood, expanded and activated with IL-15 in the rescue treatment of paediatric patients, adolescents and young adults with relapsed or refractory acute leukaemia (AL).
The main objective is to determine the safety of immunotherapy with haploidentical allogeneic differentiated adult Natural Killer cells from peripheral blood, expanded and activated with IL-15 (NKAEs) following rescue chemotherapy in paediatric patients, adolescents and young adults (relapsed or refractory AL).
The secondary objectives will be:
- To analyse the incidence of febrile neutropenia, bacteraemia, infections (viral, fungal), hematologic recovery and hospitalisation episodes.
- To assess the full remission rate (cytomorphological and according to “minimal residual disease” criteria, flow cytometry and/or molecular biology).
- To assess the immune reconstitution of lymphocyte populations and the cytotoxic activity of NK cells before and after KNAES infusion.
RESULTS
We are in the patient inclusion stage; we already have treated children who are in remission and the study is still in progress.