A trial looking at giving extra white blood cells after a mini transplant (ProT4)

This trial is looking at giving extra T cells after a mini transplant for non Hodgkins lymphoma (NHL) or chronic lymphocytic leukaemia (CLL).

Some people with NHL or CLL have a stem cell or bone marrow transplant using cells taken from their brother or sister. This is called a sibling allogeneic transplant. They often have lower doses of chemotherapy so it is sometimes called a mini (or reduced intensity) transplant.

People who have a transplant have medication to damp down the immune system (immunosuppressants) afterwards. This helps stop the new cells attacking the patient’s own cells, a condition called graft versus host disease or GVHD. But it also increases the risk of getting an infection.

T cells are lymphocytes, a type of white blood cell. They are part of our immune system. Doctors hope that giving specific T cells called CD4 cells may help boost immunity and reduce the risk of infection. In this trial they are giving extra CD4 cells from the donor a few months after the transplant. This is called a donor lymphocyte infusion (DLI).

The doctors also hope the CD4 cells will recognise and kill any lymphoma or leukaemia cells left behind – something called the graft versus lymphoma, or graft versus leukaemia (GvL) effect. If this happens it will reduce the risk of the cancer coming back.

The aim of this trial is to find out if giving extra CD4 T cells after a stem cell or bone marrow transplant will

Help stop the lymphoma or leukaemia coming back
Affect the number of people who get graft versus host disease, or how serious it is
Affect the immune system
Reduce the risk of getting an infection

Recruitment

Start 07/11/2011

End 01/11/2015

Phase

Phase 2

Who can enter

You may be able to enter this trial if you have one of the following

Follicular lymphoma
Lymphoplasmacytic lymphoma (also called Waldenstrom's macroglobulinaemia)
Small cell lymphocytic lymphoma (or Chronic lymphocytic leukaemia (CLL))

As well as that you must

Have had one course of treatment already
Be due to have a stem cell or bone marrow transplant using cells from your brother or sister (this is standard treatment, not part of the trial)
Be due to have the drugs fludarabine, melphalan and alemtuzumab (MabCampath) before your transplant
Have satisfactory blood test results
Be between 18 and 69 years old

You cannot enter this trial if you

Have problems with your liver or kidneys
Have had your transplant and have serious graft versus host disease (GVHD)
Have had your transplant and your cancer has come back
Need immunosuppressants for another medical condition
Are having treatment as part of any other clinical trial
Are pregnant or breastfeeding

Trial design

This is a phase 2 trial. It will recruit 86 people into one of two groups.

Group 1 have an infusion of extra CD4 T cells from their donor after their transplant
Group 2 don’t have any extra T cells after their transplant

Everyone taking part in this trial will have a mini stem cell or bone marrow transplant using cells from their brother or sister. About a month after your transplant you begin to lower your dose of immunosuppressant drugs, stopping completely about a month after that. About a month later the doctors will do tests to see how well the transplant has worked.

If the treatment hasn’t worked and the cancer has come back, you won’t be able to take part in the rest of the trial. But if the treatment has worked, you can go on to the take part in the rest of the trial. If so, you will be put into one of the treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in. This is called a randomised trial.

If you are in group 1 you have the T cells from your donor about 3 to 4 months after your transplant. You have them as an infusion into a vein.

If you are in group 2 you won’t have the infusion of extra T cells. You will continue to see your doctor as usual.

Hospital visits

You will see the doctors and have some tests before you take part in this trial. The tests include

Blood tests
Physical examination, including weight
Scans or tests such as CT scan, PET scan or bone marrow test

Having a bone marrow or stem cell transplant is an intensive treatment. You will see the doctors and have tests regularly after your transplant whether you take part in this trial or not.

If you are in group 1, you will need to go to the outpatients department after your transplant to give a blood sample. Then about 3 to 4 months after your transplant to have the T cell infusion. This will take about half an hour.

If you are in group 1, you will need to give extra blood samples at the start of the trial and about 3, 6, 9 and 12 after your transplant. If you are in group 2, you will just need to give an extra blood sample at the start of the trial. The research team will use these blood samples to try and find out more about cancer and its treatment.

Everyone taking part will see the doctors at 6, 9 and 12 months after your transplant, and then once a year after that.

Side effects

All treatments have some side effects. The possible side effects of a T cell infusion include

Fever or chills when you have the infusion
Graft versus host disease (mild or more severe)

There is a small risk of getting an infection from the T cells, although the research team screen the donors and check the donated cells to help prevent this.

We have more information about the side effects of a bone marrow or stem cell transplant.