A trial looking at ALETA-001 after CAR T-cell treatment for B cell non-Hodgkin lymphoma

Cancer type:

Blood cancers

Non-Hodgkin lymphoma

Status:

Open

Phase:

Phase 1/2

This trial is looking at a new type of targeted cancer drug called ALETA-001.

It is for people with B cell non-Hodgkin lymphoma Open a glossary item after CAR T-cell therapy targeting the CD19 protein.

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 T cells Open a glossary item . 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.

ALETA-001 trial diagram

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 standard treatment Open a glossary item for people who have NHL that does not go away fully with CAR T-cells.

ALETA-001 a targeted cancer drug. Open a glossary item It 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 any 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
when the best time is to give ALETA-001 after CAR T-cell treatment
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 when, 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 phase 1 Open a glossary item 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
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 - there are also specific entry conditions for each group of the Phase 1 trial.

Phase 1 Group A and B
You may be able to join these groups if all of the following apply. You:

have either diffuse large B cell lymphoma or mantle cell lymphoma that has not gone away with treatment (refractory) or has come back after treatment (relapsed)
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.
have satisfactory blood test results

Phase 1 Group C and D
You may be able to join these groups if all of the following apply before you have your chemotherapy in preparation for CAR T-cell therapy. You:

have either diffuse large B cell lymphoma or mantle cell lymphoma that has not gone away with treatment (refractory) or has come back after treatment (relapsed)
are going to be having CAR T-cell treatment as part of your treatment plan
have satisfactory blood test results
have satisfactory heart test result
have satisfactory blood oxygen levels

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)
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
have a weakened immune system after an organ transplant
have another physical or mental health condition that the trial team think would prevent you from taking part

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
are pregnant or breastfeeding

Please note – as well as the above, each group in Phase 1 has specific exclusion criteria.

Group A and B exclusion criteria are for before joining the trial. Group C and D exclusion criteria are for after your CAR-T cell treatment but before having ALETA-001.

Phase 1 Group A and B
You cannot join group A or B if any of the following apply. You:

have had any other systemic cancer treatment after CAR T-cell therapy
had side effects linked to cytokine release syndrome or side effects affecting your brain from your CAR T-cell therapy unless these were mild and have now got better. Your doctor can explain more.

Phase 1 Group C and D
You cannot join group C or D if any of the following apply before your ALETA-001 treatment. You:

had side effects linked to cytokine release syndrome or side effects affecting your brain from your CAR T-cell therapy unless these were mild and have now got better. Your doctor can explain more.
are in bed or a chair for more than half the day and you need help to look after yourself (ECOG performance status of 3 or higher)
have moderate side effects from CAR T-cells affecting an organ and this hasn’t improved. You might still be able to take part if you are having problems with blood cell production.
have a serious active infection. Your doctor can explain more.

Please note – as well as the above, the trial team are looking for people to take part in phase 2 of this trial after Phase 1 has finished. The trial team can tell you more.

Trial design

This is a phase1/2 trial. The researchers need up to 84 people to take part in the UK.

Phase 1 – Safety lead in
Phase 1 is also called the safety lead in. It has four groups A,B,C and D. 6 people join each group. So, 24 people take part in Phase 1.

In phase 1 the researchers are looking at the timing and amount (dose) of ALETA-001.

Timing (Group A and B)
People in group A and B have a PET scan Open a glossary item around 4 weeks after their CAR T-cell therapy. If the scan shows that the lymphoma hasn’t responded fully to the CAR T-cells then their doctor might recommend ALETA-001.

People in group A and B with no lymphoma seen on this scan might have ALETA-001 if their lymphoma comes back at a later date.

Timing (Group C and D)
People in group C and D have ALETA-001 10 to 18 days after CAR T-cell therapy.

Dose of ALETA-001

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

Phase 2 – dose expansion phase
More people join the trial at this phase.

Phase 2 Open a glossary item begins when researchers have found out a safe dose, and best time to give, ALETA-001 for 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.

The researchers need around 60 people to take part in phase 2.

How you have ALETA-001
You have ALETA-001 as cycles of treatment Open a glossary item . 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 in 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 Open a glossary item 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
at various points within 24 hours of 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 - Phase 2 only
The trial team would like to take blood samples before and during treatment for a genotyping Open a glossary item 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 genes Open a glossary item are important for controlling cells 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 biopsy Open a glossary item 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 have 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 might already be an inpatient after your CAR T-cell therapy if you are in Phase 1 group C or D.

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 2- 4 weeks after your first dose of ALETA-001. And then at regular points throughout the trial. How often you have a scan depends on the timing of your ALETA-001 and how well the treatment is working.

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 bone marrow Open a glossary item 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

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.

ALETA-001 aims to boost any CAR T-cells that remain in your body. So, you might have some side effects due to the CAR T-cells activity.

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. 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 risk-factor Open a glossary item 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.