A trial looking at ALETA-001 after CAR T-cell treatment for B cell non-Hodgkin lymphoma
Cancer type:
Status:
Phase:
This trial is looking at a new type of targeted cancer drug called ALETA-001.
It is for people with B cell 
who have had CAR T-cell therapy targeting the CD19 protein and either:
- the lymphoma has not responded fully to the CAR T-cells or
- the lymphoma has come back
Cancer Research UK supports this trial.
More about this trial
CAR T-cell therapy is a possible treatment for B cell non-Hodgkin lymphoma (NHL) that has not responded to other treatments.
CAR T-cell therapy is a very complex and specialist treatment. A specialist collects and makes a small change to your . After a few weeks, you have a drip containing these cells back into your bloodstream. The CAR T-cells then recognise and attack the cancer cells.
CAR T-cell therapy can work well, but not everyone’s lymphoma goes away with this treatment. Doctors can’t tell who will, or won’t, respond well. At the moment, there is no for people who have NHL that does not go away fully with CAR T-cells.
Doctors would like to improve the treatment options for people in this situation. They think that a new might help.
ALETA-001 has been designed to help to boost any CAR T-cells that are still around after CAR T-cell therapy. ALETA-001 attaches to both the lymphoma cells and the CAR T-cells. The aim is to help the CAR T cells recognise and attack the lymphoma cells.
The trial team hope ALETA-001 will help the CAR T-cells work better and kill the remaining lymphoma cells. But they are not sure. They are doing this trial to try and find out.
Everyone taking part has ALETA-001.
The main aims of the trial are to find:
- the doses of ALETA-001 that can be given safely to people
- more information about the side effects of treatment and what can help to manage them
- what happens to ALETA-001 inside the body
- whether ALETA-001 will help CAR T-cells attack lymphoma cells
This will help the trial team to work out how much, and how often, to give ALETA-001 to people in further clinical trials.
Who can enter
The following bullet points are a summary of the entry conditions for of this trial. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you.
Who can take part
You may be able to join this trial if all of the following apply. You:
- have B cell
non-Hodgkin lymphoma - have had CAR T-cell therapy that targets CD19 proteins on the lymphoma cells
- have lymphoma that your doctor can see on a scan around 4 weeks after your CAR T-cell therapy. You might be able to take part if your lymphoma goes away after your CAR T-cell treatment and then comes back (relapses) within 9 months.
- are at least well enough to be up and about more than half the day, you can look after yourself but may not be able to work (ECOG performance status 0,1 or 2)
- have satisfactory blood test results
- are willing to use reliable contraception during treatment and for 12 months after the last dose of ALETA-001 if there is any chance you can become pregnant
- are willing to use reliable contraception during treatment and for 6 months after the last dose of ALETA-001 if you are male and there is any chance your female partner could become pregnant
- are aged 16 or over
Please note - It is also possible to join the trial before your CAR T-cell therapy. You give a blood sample before your treatment. You would only be able to take part and have ALETA-001 if:
- your lymphoma does not go away completely and
- all of the above conditions apply
Who can’t take part
Cancer related
You cannot join this trial if any of these apply. You:
- are having
radiotherapy . You might be able to take part if you are having radiotherapy to help with symptoms. - have lymphoma in the
central nervous system (CNS lymphoma) - had side effects linked to cytokine release from your CAR T-cell therapy unless these were mild. Your doctor can explain more.
- have side effects from other cancer treatment that are causing you problems and the trial team think that this could prevent you from taking part
- have, or have had, another type of cancer. You might still be able to take part if you have had very early cervical cancer (in situ),
basal cell skin cancer or squamous cell skin cancer and you’ve had treatment. You might still be able to take part if you have had treatment with the aim to cure for another type of cancer, there is a low risk of it coming back and you have had no sign of the cancer for at least 2 years. You might be able to take part if you have had prostate cancer and your PSA level has been satisfactory for at least a year. - are having medicines that dampen down the
immune system (immunosuppressants). You might be able to take part if you are having small doses of steroids your body no longer produces (replacement steroids) or steroids that you inhale.
Medical conditions
You cannot join this trial if any of these apply. You:
- have an active infection or an inflammatory disease that needs treatment at the moment. Or you have an uncontrolled infection.
- have a condition other than cancer that affects your whole body (systemic disease)
- have had major surgery to your chest or tummy (abdomen) and you haven’t recovered yet
- have an immunodeficiency syndrome which you developed, or you were born with
- you have a weakened immune system after an
organ transplant
Other
You cannot join this trial if any of these apply. You:
- are allergic to ALETA-001 or anything it contains
- are taking part in another treatment related clinical trial
- have another physical or mental health condition that the trial team think would prevent you from taking part
- are pregnant or breastfeeding
Please note – As well as the above, the trial team are looking only for people with diffuse large B cell lymphoma and mantle cell lymphoma to take part in phase 2 of this trial.
Trial design
This is a phase1/2 trial. The researchers need up to 72 people to take part in the UK.
Phase 1 – Safety lead in
One or more people have the same dose of ALETA-001. The trial team check that the dose does not cause any severe side effects in this group before the next group join the trial. The researchers will also look at how well ALETA-001 works as a treatment.
The doses of ALETA-001 are changed in each group of patients until the trial team finds the best dose that:
- targets the lymphoma cells
- does not cause side effects that are too severe
The researchers need around 12 people to take part in phase 1. Everyone taking part has NHL and has had CAR T- cell therapy.
Phase 2 – dose expansion phase
More people join the trial at this phase. Only people with specific types of NHL can take part, you must have either:
begins when researchers have found out a safe dose of ALETA-001 to give several people at the same time. The aim of this part of the trial is to see how well ALETA-001 is working and to learn more about how safe it is.
How you have ALETA-001
You have ALETA-001 as . You have it as a drip into the bloodstream, once every 2 weeks. It takes around 2 hours each time.
You might have the same dose of ALETA-001 each time. Or you might have a lower dose the first time you have it, followed by an increased dose the other times. Your trial doctor will explain the dose, or doses, you have.
You might stay on treatment on the trial for up to a year, as long as your lymphoma is not getting any worse and the side effects are not too bad.
Tests during treatment
You have PET-CT scans at regular points during treatment. This is to see how your lymphoma is responding to treatment. We have more information about this in the ‘hospital visits’ part of this summary.
If the scans show that your lymphoma is growing, you stop ALETA-001 as it is no longer working for you. Your trial doctor will discuss your next treatment options with you.
Samples for research
You give blood samples for research at set points during the study. This is:
- before your first treatment
- 24 hours after your first treatment
- before every dose of ALETA-001
The researchers use the samples to look at:
- what happens to ALETA-001 inside the body
- if ALETA-001 is helping your CAR T-cells target the lymphoma cells
Blood samples before CAR T-cell therapy
You might have already given one or more blood samples before your CAR T-cell treatment. The trial team use these to understand more about how ALETA-001 works if you join the trial.
These samples are optional. This means if you did not give blood samples before your CAR T-cell treatment you can still take part in the trial.
Genotyping research blood test
The trial team would like to take blood samples before and during treatment for a test. You might also have given a blood sample for genotyping testing before your CAR T-cell therapy.
Genotyping allows scientists to look at which are important for controlling in the body. The trial team want to look at the genes that control your lymphoma cells.
You can say no to having the genotyping blood tests and still take part in the main trial.
Tissue sample for research - Phase 2 only
The trial team will ask your permission to look at a tissue sample of your lymphoma from a you have had before. If you don’t have a suitable sample, the trial team will ask if you are willing to have a biopsy before you start treatment on the trial.
The trial team may ask for another biopsy sample after you receive your first dose of ALETA-001 if this is appropriate.
They compare the two tissue samples to see what affect ALETA-001 is having on your lymphoma.
You don’t have to agree to giving new tissue samples, or for the team to access to an older sample. You can say no and still take part in the main trial.
Blood and tissue samples for future research
The trial team ask your permission to store any blood or tissue samples they have not used for future cancer research.
You can say no to this and still take part in the trial.
Hospital visits
You see a doctor and have some tests before taking part. These might take a few days to be completed. And you might have to travel to another hospital to have one or more tests. The tests include:
- a
physical examination , including vital signs and weight - blood tests
- urine test
- pregnancy test – if there is any chance that you could become pregnant
- heart trace (
ECG ) - PET-CT scan
You have your first dose of ALETA-001 as an inpatient and stay overnight in hospital. This is so your treatment team can monitor you for any side effects for at least 24 hours. You then stay within an hour of the hospital for another 48 hours so you can go in quickly if you have any side effects. If you live more than an hour away from the hospital, the trial team will arrange for somewhere you can stay.
You will be seen by your trial doctor and nurse every 2 weeks. This is on the day of your ALETA-001 infusion. You have routine blood tests the day after your ALETA-001 infusion. You see your trial treatment team more often if you need to.
You have your other ALETA-001 doses in hospital. You will probably spend most of the day in hospital. Or you might need to stay in hospital overnight and then within an hour of the hospital for another 48 hours. Again, this is so your treatment team can monitor you for possible side effects and you can get help quickly if you need it. Your doctor will let you know if you need to stay in hospital.
You have some tests before each dose of ALETA-001 to make sure you are well enough for treatment. These might include:
- weight and vital signs
- blood tests
- urine test
You have a heart trace (ECG) or a physical examination if your trial doctor thinks this is needed.
You have your vital signs checked for up to 4 hours after your drip finishes each time.
You have a PET-CT scan 4 weeks after your first dose of ALETA-001. And then:
- 8 weeks after your first dose
- 12 weeks after your first dose and then
- every 12 weeks until 11 months if you are still taking part in the trial
You might have a bone marrow test if you have mantle cell lymphoma, and your scans show your lymphoma has gone away completely. The test checks there is no lymphoma in the that cannot be seen on a scan.
You see the trial team within 28 days of stopping ALETA-001. You have some tests at this visit. These are the same as you had when joining the trial.
Follow up
Once you stop treatment, if you have side effects caused by the ALETA-001, the trial team will see you or contact you at least once a month. This is to monitor the side effects until:
- they get better
- you start a new cancer drug or other cancer treatment
This might involve a visit to hospital. The trial team try and make this at the same time as your routine clinic appointments. Or the team may phone you to see how you are getting on.
You don’t have to have any further hospital visits as part of this trial. The trial team look at your medical notes from your hospital clinic visits or speak to your GP to see how you are getting on. They might phone you if needed. This is so they can see whether your cancer is getting better or worse and find out if you have any side effects.
Side effects
The trial team monitor you during treatment and afterwards. Contact your advice line or tell your doctor or nurse if any side effects are bad or not getting better.
This is the first time that ALETA-001 is being used in people. There might be side effects we don’t know about yet. Based on laboratory studies one possible side effect might be an allergic reaction during, or after, having the drip. Symptoms include:
- a high temperature (fever) or chills
- flushing of the skin
- itchy skin
- skin rash or hives
- swelling, for example around the lips
- feeling or being sick
- feeling short of breath
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CAR T-cell treatment affects the immune system. This can cause serious side effects. They could happen during treatment, or after treatment has finished. In some cases, these side effects could be life threatening. If you have any side effects tell your doctor or nurse as soon as possible. |
Possible side effects include:
- cytokine release syndrome (CRS) - symptoms of CRS can be mild (fever and muscle ache), moderate (such as low blood pressure and difficulty breathing), or severe (which could be life threatening)
- side effects affecting the brain which may include headaches, a change in awareness of your surroundings and how you respond, speech changes, brain swelling or seizures (fits)
- a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
- viral infections coming back – these are virus’ that have been inactive in your body
- low levels of certain
antibodies in the blood (hypogammaglobulinemia) – this means you may be more likely to get infections - tumour lysis syndrome (TLS) from the CAR T-cells killing large numbers of lymphoma cells. These changes can affect your heart or kidneys. Your doctor will closely monitor your blood levels during treatment.
- a very small chance of developing a second cancer in the future
You will also be given a card with your team's contact details on it that you must carry with you while you are on the trial.
We have more information about CAR T-cell therapy including its possible side effects.
Genotyping research side effects
When looking at cancer related genes, sometimes researchers see other genes that could be a possible for other medical conditions. This does not mean you would go on to develop these conditions, but the gene may be passed on to your children.
Your trial doctor can give you more information about this. There are genetic specialists who can help and support you if needed.
Location
Recruitment start:
Recruitment end:
How to join a clinical trial
Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.
Chief Investigator
Dr Sridhar Chaganti
Supported by
Cancer Research UK
Other information
This is Cancer Research UK trial number CRUKD/23/001
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
