A trial of CD19 and CD22 CAR T-cells to treat blood cancers in children and young people (CARPALL)

Cancer type:

Acute leukaemia

Acute lymphoblastic leukaemia (ALL)

Children's cancers

Leukaemia

Status:

Results

Phase:

Phase 1

This trial was for children and young people with acute lymphoblastic leukaemia (ALL) that either:

had come back after treatment
was likely to come back after treatment

Children and young people with a leukaemia that had the CD19 or CD22 protein could take part.

The trial was open for people to join between 2016 and 2021. The team reported results in 2019 and 2024.

More about this trial

Chemotherapy can help many children and young people who have leukaemia. But for some, their cancer comes back after treatment (relapse).

Treatment when this happens is usually further chemotherapy or a bone marrow transplant. But this doesn’t always work, and researchers are looking at new ways to treat these children and young people.

In this trial researchers used immune system Open a glossary item cells called T cells. These cells are very good at helping us fight infections, but they aren’t so good at telling the difference between a normal cell and a cancer cell.

Some blood cancer cells have proteins called CD19 or CD22 on the surface. Some have both proteins.

The researchers collected T cells of people taking part in the trial and made a change to them in the laboratory. This is so that they could recognise the CD19 or CD22 protein. These altered T cells are called CD19 or CD22 CAR T-cells.

Everyone taking part had either:

CD19 CAR T-cells or
CD19 and CD22 (CD19/CD22) CAR T-cells

They had treatment as a drip into a vein (intravenous infusion). The researchers thought that the CAR T-cells would attack and kill cells that have the CD19 or CD22 protein.

The main aims of this trial were to find:

if it is possible and safe to give CD19 and CD19/CD22 CAR T-cells to children and young people with a blood cancer that has come back or is likely to come back after treatment
how well CD19 and CD19/CD22 CAR T-cells work
how long CD19 and CD19/CD22 CAR T-cells stay in the body

Summary of results

CAR T-cells can work well for children and young people with leukaemia that has not responded to treatment or has come back. Sometimes targeting just CD19 can allow the protein to change and hide from the CAR T-cells.

The researchers developed a CAR T-cell treatment that targets both CD19 and CD22. The results so far have shown that if the leukaemia comes back after this treatment, the protein doesn’t change to hide from the T cells.

The researchers say that the side effects were as expected and generally not too severe.

Results

The trial treated people who had CD19 or CD22 positive B cell acute lymphoblastic leukaemia (ALL). And their leukaemia had either:

not gone away with treatment
come back after treatment

There were 2 groups of people taking part in the trial.

The researchers looked at the CAR T-cells in one group of people at a time.

Group 1 – CD19 CAR T-cells

The CAR T-cells for group 1 targeted the CD19 protein.

17 people took part in group 1.

The researchers were able to make CAR T-cells for 14 out of the 17 people. All 14 had the CAR T-cell treatment.

At 3 months, in 12 out of the 14 people, the leukaemia went away completely. There was no sign of the leukaemia in their blood or bone marrow including when using a minimal residual disease Open a glossary item (MRD) test.

The trial team looked at how long the CAR T-cells stayed in the body of people taking part. They found that this was around 7 months.

The leukaemia came back in 6 of the 12 people whose leukaemia went away at first. This is called relapse.

5 people’s leukaemia had no CD19 at relapse
1 person’s leukaemia had the CD19 protein at relapse

At 1 year after treatment:

9 out of 12 people whose leukaemia went away after the CAR T cells were still alive
5 out of 12 people whose leukaemia went away after the CAR T cells were still alive with no sign of leukaemia

Side effects
Nearly everyone had side effects of treatment.

Most people had a drop in blood cells. 11 out of 14 people had a drop in blood cells that lasted longer than a month. Or started around a month after treatment.

13 out of 14 people had cytokine release syndrome (CRS). This is because CAR T-cell therapy stimulates the immune system to make large amounts of cytokines Open a glossary item . Nobody had severe CRS.

Side effects affecting the brain (neurological) were generally mild and did not last long. 6 out of 14 people had mild to moderate neurological side effects including:

difficulty speaking
burning or pins and needles sensations
feeling extremely sleepy

One person had a severe side effect affecting brain function.

Group 2 – CD19 and CD22 CAR T-cells

The researchers used what they had learned from group 1 to make changes for group 2.

They found that for some people in group 1 the leukaemia came back, and it no longer had the CD19 protein. This means the protein had changed (mutated) so the CAR T-cells could no longer recognise it.

The researchers made the CAR T-cells to target both the CD19 and CD22 protein for group 2.

13 people joined group 2.

The researchers were able to make CAR T-cells for all 13 people. 1 person was unable to have treatment due to an uncontrolled infection.

At 2 months, in 10 out of the 12 people, the leukaemia went away completely. There was no sign of the leukaemia in their blood or bone marrow including when using a minimal residual disease (MRD) test.

The trial team looked at how long the CAR T-cells stayed in the body of people taking part. They found that this was around 3 - 4 months.

The leukaemia came back (relapsed) in 3 out of the 10 people whose leukaemia went away. And a further 5 out of 10 people had minimal residual disease. Everyone had CD19/CD22 positive leukaemia when it had come back.

At 1 year after treatment:

9 out of 10 people whose leukaemia went away after the CAR T cells were still alive
6 out of 10 people whose leukaemia went away after the CAR T cells were still alive with no sign of leukaemia

Side effects
Most people had side effects of treatment including a drop in blood cells.

11 out of 12 people had mild or moderate cytokine release syndrome (CRS). No one had severe CRS.

5 out of 12 people developed mild or moderate toxicity Open a glossary item to the nervous system which got better by itself. This is also called immune effector cell associated neurotoxicity syndrome (ICANS).

1 person developed severe toxicity to the nervous system with:

a lowered conscious level – this a measurement of awareness and understanding of surroundings
weakness
problems with speech

We have more information about the side effects of CAR T-cells in our immunotherapy section.

Conclusion
The trial team concluded that targeting both CD19 and CD22 may help stop proteins changing and hiding on leukaemia cells.

They say that this is a small trial, and so they would like to develop further studies looking at CD19/CD22 CAR T-cells.

More detailed information
There is more information about this research in the references below.

Please note, the information we link to here is not in plain English. It has been written for healthcare professionals and researchers.

Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR
S Ghorashian and others
Nature Medicine, 2019. Volume 25, pages 1408–1414.

CD19/CD22 targeting with cotransduced CAR T cells to prevent antigen-negative relapse after CAR T-cell therapy for B-cell ALL
S Ghorashian and others
Blood, 2024. Volume 143, number 2, pages 118-123.

Where this information comes from

We have based this summary on the information in the articles above. These have been reviewed by independent specialists (peer reviewed Open a glossary item ) and published in medical journals. We have not analysed the data ourselves.