A study looking at treating children who have high risk acute lymphoblastic leukaemia with modified immune cells (CD19 TPALL)

Cancer type:

Acute leukaemia

Acute lymphoblastic leukaemia (ALL)

Blood cancers

Children's cancers

Leukaemia

Status:

Results

Phase:

Phase 1/2

This study used gene therapy to treat children with acute lymphoblastic leukaemia (ALL).

The study was for children and young people up to and including the age of 18. We use the term ‘you’ in this summary, but of course if you are a parent, we are referring to your child.

More about this trial

Stem cell transplant using cells taken from someone else (a donor) can be used to treat ALL.

After a stem cell transplant, you might have some more immune system cells called lymphocytes Open a glossary item , also taken from your donor. But donor lymphocytes are not very good at getting rid of the leukaemia completely. And they can cause a condition called graft versus host disease (GVHD) because the donor’s immune cells attack some of your normal cells.

In this study, researchers carefully picked out the lymphocytes from the donor and changed some of them in the laboratory. They wanted to make them better at attacking leukaemia cells, but less likely to cause GVHD.

This treatment is called CD19CAR T-cell therapy (and the modified lymphocytes are called CD19CAR T-cells CTL). It is a type of gene therapy. Researchers hoped it would reduce the risk of ALL coming back after a stem cell transplant.

In the second part of the study the researchers used some of the donor lymphocytes (that have not been changed in a laboratory) in addition to the CD19CAR T-cells. They wanted to see if these unmodified lymphocytes (called lymphocytes vaccine) may help the CD19CAR T-cells stay longer in your body to attack the leukaemia cells.

The children and young people who took part in this trial had a type of ALL that affects the B cells. They either had:

their first stem cell transplant
had a stem cell transplant but their leukaemia had come back and they were going to have another one

Whichever situation they were in, their doctors thought there was a high risk of the leukaemia coming back after the transplant.

The main aims of the study were to learn more about this type of treatment, how well it worked and how safe it was.

Summary of results

The study team found that CD19CAR T-cells lasted longer in people’s blood when used with the vaccine.

This was a phase 1/2 study. 11 children and young people took part.

Everyone had the CD19CAR T-cells. Some had it before and after their 2nd stem cell transplant. Others had it when their leukaemia had come back after their 1st stem cell transplant.

Initially the CD19CAR T-cells were given by itself to see how they worked.

Afterwards the CD19CAR T-cells were given together with the vaccine to see if this would make the CD19 CAR T-cells last longer in the body and work better.

CD19CAR T-cells ONLY
The first 6 children had CD19CAR T-cells only.

After treatment researchers took blood samples to see how many of the CD19CAR T-cells were in the blood and how long they stayed there.

They found CD19CAR T-cells in the blood of 2 children. For 1 child CD19CAR T-cells could be found in the blood for a week. For the other child it was for a month.

To find how well the leukaemia responded to CD19CAR T-cells the team looked at the number of leukaemia cells in the bone marrow. This is called minimal residual disease (MRD).

A month after treatment for:

2 children there was no MRD detected (a complete response)
1 child their MRD had reduced (a partial response)
2 children their MRD had stayed the same (stable disease)
1 child their MRD got worse (no response)

Researchers said that although CD19CAR T-cells were safe, the time it stayed in the body and how well it worked was limited.

CD19CAR T-cells and vaccine
6 children were in this part of the study. This included the child who had a partial response to CD19CAR T-cells only.

The researchers took blood samples as before to find how many of the CD19CAR T-cells were in the blood and for how long they stayed there.

They found CD19CAR T-cells in the blood of 4 children. The length of time they could be found in blood ranged from 1 month to 3 months.

The team also looked at the MRD for how well the CD19CAR T-cells and the vaccine worked. A month after treatment:

3 children had a complete response
1 child had stable disease
2 children had no response

The study team concluded that CD19CAR T cells were safe and the vaccine improved the length of time CD19CAR T-cells stayed in the blood. Unfortunately, the leukaemia came back (relapsed) in most people.

The team are now looking at stronger CD19 CAR T-cells to see if they can treat relapsed ALL in children more successfully.

We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed Open a glossary item ) and published in a medical journal. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.