A trial of ponatinib for chronic myeloid leukaemia or Philadelphia positive acute lymphoblastic leukaemia (PACE)

Cancer type:

Acute leukaemia

Acute lymphoblastic leukaemia (ALL)

Blood cancers

Chronic leukaemia

Chronic myeloid leukaemia (CML)

Leukaemia

Status:

Results

Phase:

Phase 2

This trial looked at a drug called ponatinib for chronic myeloid leukaemia (CML) or some types of acute lymphoblastic leukaemia (ALL). It is for people whose leukaemia had not responded to, or had got worse while having, other treatments.

Most people with CML, and some people with ALL, have a change (mutation Open a glossary item ) to a gene in their leukaemia cells. Doctors call this Philadelphia chromosome positive . It affects a protein called BCR-ABL1 which tells the body to make too many white blood cells.

Certain drugs called tyrosine kinase inhibitors Open a glossary item (TKIs) can block the BCR-ABL1 protein. But sometimes these drugs don’t work very well, or they stop working (the leukaemia becomes resistant to them).

In this trial, researchers looked at a new TKI drug called ponatinib. The people taking part have already had other TKIs such as imatinib, nilotinib (Tasigna), dasatinib (Sprycel), or bosutinib but their leukaemia was not responding. Some people taking part had a genetic change in their leukaemia cells, called T315I, which makes them resistant to all other TKIs. The aim of this trial was to see if ponatinib helped people with CML or Philadelphia positive ALL who are in one of the following situations

Their leukaemia was resistant to other TKI drugs
They could not take other TKI drugs because of bad side effects
They had the T315I gene change in their leukaemia cells

Summary of results

The trial team found that ponatinib did help people with chronic myeloid leukaemia (CML) and people with Philadelphia positive acute lymphoblastic leukaemia (ALL).

When the researchers analysed the results they looked at the blood counts to see if they had gone back to more normal levels. This is called haematological response.

They also looked at the bone marrow Open a glossary item to find out how many cells containing the Philadelphia chromosomes were present. This is called cytogenetic response.

They also looked at how much BCR-ABL1 was in their blood. This is called a molecular response.

Of the 449 people who took part in this trial, the researchers were able to look at the results of 444. The researchers analysed the results according to whether the people taking part had Philadelphia positive ALL or by the stage of their CML.

267 people had CML that was in the chronic phase
83 people had CML that was in the accelerated phase
62 people had CML that was in the blast phase
32 people had Philadelphia positive ALL

Of the 267 people who had chronic phase CML

94 out of every 100 people (94%) had blood counts that had returned to normal (a complete haematological response)
46 out of every 100 people (46%) had no abnormal Philadelphia chromosomes in their bone marrow (a complete cytogenetic response)
34 out of every 100 people (34%) had a very low amount of BCR-ABL 1 in their blood (a major molecular response)

Of the 83 people who had accelerated phase CML

55 out of every 100 people (55%) had blood counts that had almost returned to normal (a major haematological response)
24 out of every 100 people (24%) had no abnormal Philadelphia chromosomes in their bone marrow (a complete cytogenetic response)
16 out of every 100 people (16%) had a low amount of BRC-ABL 1 in their blood (a major molecular response)

Of the 62 people who had blast phase CML

31 out of every 100 people (31%) had blood counts that had almost returned to normal (a major haematological response)
18 out of every 100 people (18%) had no abnormal Philadelphia chromosomes in their bone marrow (a complete cytogenetic response)

Of the 32 people who had Philadelphia positive ALL

41 out of every 100 people (41%) had blood counts that had almost returned to normal (a major haematological response)
38 out of every 100 people (38%) had no abnormal Philadelphia chromosomes in their bone marrow (a complete cytogenetic response)

The most common side effects were

A drop in blood cells
Rash, dry skin
Tummy (abdominal) pain
Blood clots affecting the blood vessels of the heart, lower legs and brain

The trial team concluded that ponatinib could help people with CML or Philadelphia positive ALL.

We have based this summary on information from the team who ran the trial. 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. We have not analysed the data ourselves.