LION-1 study
- Patients with chronic lymphocytic leukaemia (CLL), mantle cell lymphoma (MCL), breast cancer, ovarian cancer or adrenal cortex cancer are eligible to participate in the LION-1 study.
- Patients can only participate if standard therapies are not effective or no longer effective for them.
- LION-1 is investigating how immunotherapy with special, genetically modified T cells – ROR1 CAR T cells – affects the progression of cancer and what side effects occur.
Study status: The study is accepting patients (recruitment open).
Cancer develops because of changes in the genetic material of cells. In principle, our immune system can recognise and kill such altered cells. However, cancer cells are very good at "camouflaging" themselves, for example, by constantly changing.
Modern immunotherapies can help the body's own immune system to better recognise and kill cancer cells. There are various approaches with different mechanisms of action.
In CAR-T cell therapy, the body's own immune cells, known as T cells, are taken from the blood and genetically modified. This gives them an artificial recognition site on their surface: the so-called chimeric antigen receptor (CAR). This receptor enables the immune cells to recognise the cancer cells and attack them in a targeted manner.
In the LION-1 study, researchers are investigating how effective and tolerable a new variant of CAR-T cell therapy is. The receptor on the T cells recognises a protein molecule on the tumour cells called ROR1. This new therapy is called ROR1-CAR-T cell therapy.
- You can read more about the specific goals of the scientists with LION-1 in the section What is the aim of the LION-1 study?.
Which types of cancer are covered by LION-1?
Patients suffering from chronic lymphocytic leukaemia (CLL), mantle cell lymphoma (MCL), breast cancer, ovarian cancer or adrenal cortex cancer are eligible to participate in the LION-1 study. They must also meet various requirements with the most important being:
- Conventional therapies have not been effective.
- The patient is not physically impaired or requires only minimal support.
- The participants' cancer cells carry the biomarkers ROR1 on their surface.
What is the aim of the LION-1 study?
LION-1 stands for the study title "A first-in-human clinical trial to evaluate the safety and tolerability of genetically modified T cells in ROR1-positive tumours". It describes therapy with a new variant of CAR-T cells, known as ROR1-CAR-T cells.
Objectives of the LION-1 study
Scientists involved in the LION-1 study want to achieve various objectives, and aim to:
- Find out how safe treatment with ROR1-CAR-T cells is.
- Determine what acute and long-term side effects occur.
- Establish the dosage at which the study drug is effective and how well it works.
Patients with chronic lymphocytic leukaemia, mantle cell lymphoma, breast cancer, ovarian cancer or adrenal cortex cancer can participate in the LION-1 study.
However, participation does not depend solely on the type of cancer. There are other requirements, some of which vary depending on the type of tumour and must be assessed on an individual basis.
You can find out what these requirements are by clicking on the link for the relevant type of cancer:
The LION-1 study is an open-label, multicentre, single-arm phase I study:
- Open-label study: Both the study doctors and the participants know which treatment is being used. Experts also refer to this as an open study or an open-label study.
- Multicentre study: Patients can currently participate at Würzburg University Hospital. Recruitment at other NCT study centres is planned.
- Single-arm study: All participants receive the same treatment and there is no control group.
- Phase I study: The treatment is being tested in humans for the first time in this exact form.
During this meeting, the study doctor will explain the study and any possible risks to participants in detail. If they wish to participate, they must submit a written declaration of consent. Signing this form does not automatically mean that patients will be able to participate. First, doctors must check whether they are suitable for the study.
(2) Preliminary examinations to determine suitability
To determine whether participants are suitable for the study, they undergo a thorough physical examination. Blood is also taken and examined. For women who may become pregnant, doctors perform a pregnancy test.
In addition, the doctors require the following information:
- personal details (age, gender, ethnicity, etc.)
- current medical history with all relevant findings and information about previous treatments
- information about previous illnesses and comorbidities
- information on any impairments (performance status according to ECOG status or Karnofsky Performance Status)
- information on current and previous medications and therapies, and reactions to them
- information on health-related quality of life
In addition, further instrumental and imaging examinations may be necessary, possibly including the removal of tumour tissue. With the help of the information and findings collected in this way, the study physicians can decide whether the patient is suitable for the study. If this is the case, the process continues as follows.
(3) Leukapheresis
Leukapheresis takes place approximately 4 weeks before the start of treatment with the study drug. This involves isolating white blood cells (including T cells) from the participant's blood. The study drug is then produced from the T cells.
Leukapheresis is performed as follows:
- The blood is passed through a special device via a vein in the arm: this filters out the white blood cells. These are then used to produce CAR-T cells in the laboratory.
- The blood is then returned to the body via a second venous access.
- Leukapheresis takes 3 to 5 hours and is usually painless.
- This process takes place at the study centre.
Along with leukapheresis, the doctors repeat the tests for viral infections.
(4) Treatment
Admission to hospital: Participants are admitted to hospital approximately 5 days before the first treatment with the study drug. During this time, examinations and preparations for therapy are carried out.
Preparatory chemotherapy: To ensure that the treatment is as effective as possible, it is first necessary to remove some of the immune cells from the blood. Experts refer to this as lymphodepletion. This allows the modified immune cells in the study drug to spread more effectively and prevents them from competing with existing immune cells. Participants receive a special chemotherapy which has been previously studied and approved for this purpose, over a period of 3 days.
Treatment: Two days after chemotherapy, patients receive the study drug. It contains their own genetically modified CAR-T cells. The drug is administered via a single infusion into an arm vein or a central venous catheter. This takes about 30 minutes and is usually painless.
Monitoring: During and after therapy, the treating physicians monitor the participants very closely. This ensures that side effects are quickly identified and treated if necessary.
(5) Follow-up care after treatment
After discharge from the clinic, participants visit the study centre at regular intervals for examinations:
- Weekly in the first month
- Every 2 weeks in the second month
- Once a month from the third to the sixth month
- Once after 9 months and again after 12 months
Because the study drug contains genetically modified cells, annual follow-up examinations are required by law for a period of 15 years. After the follow-up examinations in the first year, participants are therefore asked to visit the study centre once a year or are contacted by telephone.
These are the potential benefits of participating in the LION-1 study:
- For patients who have already exhausted all standard and proven treatment options, participation in the LION-1 study may open another treatment option.
- The study therapy offers the chance of a potentially effective treatment that can slow down tumour growth or even shrink the tumour. In the best-case scenario, this can help to prolong life expectancy.
- If the treatment is successful, tumour-related complaints and symptoms may also improve, which can increase quality of life.
- The study results will contribute to new findings that will help future patients. With your consent, blood and tissue samples taken during the study can be stored for future research projects.
However, there may also be disadvantages to participating in the LION-1 study:
- The immunotherapy with ROR1-CAR-T cells that is being investigated may involve risks and side effects. These can vary in severity.
- The necessary examinations may also involve certain stresses or possible risks – for example, through blood sampling, tissue sampling, imaging or other medical tests.
- In addition, the treatment is being tested on humans for the first time as part of the LION-1 study. It is therefore not yet known how well it is tolerated and what side effects may occur in humans.
Important to know: The study doctors will provide you with comprehensive information about all possible risks, side effects and examinations and will help you to make a well-informed decision. They can also inform you about treatment options that are available in your situation instead of participating in the study.
You will have sufficient time to decide whether you want to participate in the study. Participation is voluntary, and you can withdraw from the study at any time without giving a reason. Ask questions if there is anything you do not understand
Where is the study being conducted?
Cancer patients can participate in the LION-1 study at the University Hospital of Würzburg (UKW). The possibility of participating in other study centres within the NCT (Cologne, Berlin) is currently being prepared.
What costs will participants incur?
Participation in the study is free of charge for patients. You will not receive any expense allowance or payment. However, it is possible to be reimbursed for any travel expenses incurred to the study centre.
If you have any questions about the financing of the study, you can ask the study team, for example during the informational meeting.
A total of up to 46 patients can participate in the study. They will be divided into 2 groups:
- One group comprises people with CLL or mantle cell lymphoma – i.e. blood cancers.
- The other group consists of people with solid tumours, namely breast cancer, ovarian cancer or adrenal cortex cancer.
Each group can include a minimum of 5 and a maximum of 23 participants.
Recruitment is currently open. This means that the study is still accepting participants – probably until December 2027. Those interested can find out how many places are still available from the coordinating study centre.
In principle, any oncologist can register patients for LION-1.
Treating oncologists can register patients they consider suitable at Lion-1-at-ukw.de. The nearest study centre will then contact them and request some preliminary information about the patients’ condition. The study doctors will then check whether participation is possible.
Cancer patients who are interested should therefore first talk to their treating physician. This will clarify whether the study is suitable for them. If this is the case, the physician can contact the study centre.
If participation in the study is possible, an informational meeting will follow at one of the study centres.
Scientific publications (selection)
Berger C, Sommermeyer D, Hudecek M, et al. Safety of targeting ROR1 in primates with chimeric antigen receptor-modified T cells. Cancer Immunology. 2015 Feb. 3(2):206-16. doi: 10.1158/2326-6066
Hudecek M, Schmitt TM, Baskar S, et al. The B-cell tumour-associated antigen ROR1 can be targeted with T cells modified to express a ROR1-specific chimeric antigen receptor. Blood. 25 November 2010;116(22):4532-41. doi: 10.1182/blood-2010-05-283309.
Hudecek M, Lupo-Stanghellini MT, Kosasih PL, et al. Receptor affinity and extracellular domain modifications affect tumour recognition by ROR1-specific chimeric antigen receptor T cells. Clin Cancer Res. 2013 Jun. 15;19(12):3153-64. doi: 10.1158/1078-0432
Turtle CJ, Hanafi LA, Berger C, et al. Immunotherapy of non-Hodgkin's lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified T cells. Sci Transl Med. 7 September 2016;8(355):355ra116. doi: 10.1126/scitranslmed.aaf8621.
This study description was prepared by authors from the Cancer Information Service, under the direction of Dr. S. Weg-Remers, based on the study documentation.