CRIS Unit for Translational Research and Clinical Trials in Hematology

Research
Principal Investigator: Dr. Joaquín Martínez
Centres: 12 de Octubre University Hospital in Madrid.
Timeline: 2011 – 2018.

Background:

Haematology or blood cell tumours are cancers which are, to a great extent, currently incurable. They are the 4th group of tumours in Spain, with almost 30,000 new cases per annum, of which only 50% are curable. They can be controlled in a large part, but, in many cases, there are quite unpredictable relapses. Research in this field is therefore indispensable.

Project Description:

This service combines clinical research on patients and laboratory research, within the assistance service for haematology tumours at H12O hospital. The service provides treatment to hospital patients and outpatients and also implements clinical trials. Operation of this unit allows a first-hand research of these tumours, which are currently, to great extent, incurable.

 

Advances made in 2018/19:

The HUNET-CRIS Unit has received accreditation from Madrid’s Regional Government for Phase 1 trials. It is currently conducting 130 clinical trials and is now fully operational. So much so that the number of treatment stations will be expanded from 3 to 8, thus substantially increasing the unit’s patient treatment capacity. Since 2013, when the unit first opened, it has treated more than 400 patients. The innovative treatments used have proven to be safe, since the percentage of toxicity derived from them has been very low, and there have been no deaths resulting from treatment.

One of the key features of the HUNET-CRIS Unit is that it is always at the very forefront of research and treatments. It is currently providing next generation cellular therapy treatments. These include therapies with NK cells in cases of myeloma and myeloid leukaemia, as well as revolutionary CAR therapies (see illustration) in multiple myeloma and acute myeloid leukaemia.

– PICTURE –

Advances in Lymphoma:

One of the most important achievements made by the HUNET-CRIS Unit in the treatment of lymphoma is the use of CAR. As we can see in the previous illustration, it involves adding certain molecules to the patient’s immune cells, which act as detectors of the cells causing the tumour. These molecules are called CAR (Chimeric Antigen Receptors). The trial will use T lymphocytes taken from the patient, cells that normally focus on destroying tumour cells but that in these patients are incapable of rejecting them. These cells will be extracted, purified and modified by means of genetic engineering so that their surfaces present molecules capable of recognising the pathological cells. The molecule that will act as a detector of tumour cells in this trial will be an antibody against CD19, which will identify and bond specifically with the CD19 marker in the target tumour cell. This way, the T lymphocyte will be able to identify and bond with the tumour cell and act as it would do under normal circumstances, by destroying it. This trial is part of a global clinical macro-trial offering an exceptional opportunity to patients when conventional treatments are ineffective.

One of the most pressing problems in chronic Myeloid Leukaemia is how to monitor and swiftly detect the reappearance of tumour cells. The sooner they are detected, the sooner action can be taken and more effective it is. In this context, the group has published in the journal Haematologica a new extremely sensitive detection method for minimal residual disease based on the patient’s blood samples.

Advances in Myeloma:

One of the major advances made by the HUNET-CRIS Unit is the development of the first treatments based on combinations of four drugs that pursue a curative target for the first time, since thus far the majority of treatments have been aimed at achieving the chronification of the disease. Furthermore, as noted previously, the HUNET-CRIS Unit will be one of only two centres in Spain taking part in a promising international clinical trial to fight myeloma using treatments based on CAR-T.

Another of the innovative lines pursued by the HUNET-CRIS Unit is the use of antibodies, a form of immunotherapy treatment, in cases of myeloma. The antibodies act as guided missiles, which bond to a target (in this case a molecule of the tumour cell) and deactivate it, alter it, or mark it out so that another cell can destroy it. One of the most revolutionary treatments involves using double antibodies, known as bispecific antibodies, which bond at one end to a tumour cell and at the other to the T lymphocytes. T lymphocytes are cells that specialise in destroying tumour cells; so, when they adhere to the tumour cell, they can eliminate it more efficiently.

Furthermore, over the last year, the lab run by Dr. Joaquín Martínez has obtained very significant results about the importance of the metabolism of mitochondria and their relationship with myeloma. Mitochondria are the energy generator within a cell. They can create different types of energy depending on the circumstances. The type of energy generated can affect cell behaviour, so this is hugely important in the development of cancer. The results obtained, which will be published over the course of this year, could also lead to the appearance of highly innovative treatments.

Achievements in 2016:

The unit, authorised by the Madrid Regional Government for Phase I trials, is currently fully operative, with more than 80 clinical trials under way. Some of these trials have allowed verifying the safety of experimental treatments, which has resulted in Phase II trials that purport to confirm the treatments’ effectiveness. An example is the treatment of myeloma with NK cells in multiple myeloma. Furthermore, the Research Unit is showing good results from a scientific standpoint.

 

In the field of Preclinical Research, an article has recently been published in the prestigious publication Blood, establishing the molecule PAK4 as a new therapeutic target in multiple myeloma (add LINK to Pubmed). Likewise, another myeloma project, presented in the ASHA (American Society of Haematology) Annual Congress 2016, is about to be published. Significant work has been carried out in the field of Acute Myeloid Leukaemia and myelodysplasia, to be published during 2017.

 

In the field of Clinical Research, 2 Phase I clinical trials have been prepared with a proposal by the investigator. This means that the laboratory results directly translate to the design of a clinical trial. These were approved in 2016 and will be implemented during 2017. There are currently a large amount of clinical trials underway: 12 Phase I Trials, with 43 patients; 5 Phase I/II Trials, with 9 patients; and 27 Phase II Trials, with 85 patients. The group has taken part in more than 35 research articles, 12 of them in high-impact publications. These include two articles in Blood, one in the New England Journal of Medicine, one in Lancet Oncology and one in the British Journal of Haematology.