British Society for Haematology. Listening. Learning. Leading British Society for Haematology. Listening. Learning. Leading
05 August 2019

A new drug is showing potential as a treatment for infants with an aggressive form of acute leukaemia, according to Australian researchers.

The survival rate for infant MLL-rearranged leukaemia is less than 50%. However, researchers at the Children's Cancer Institute in Sydney have demonstrated in mouse models of MLL-rearranged leukaemia that a combination of a new drug CBL0137 and chemotherapy resulted in the leukaemia becoming undetectable.

The combined therapy can be used in a wide range of cancers including solid tumours such as renal cell carcinoma and small cell lung cancer. Trials are already under way in adults in America and so far, the drug has been well tolerated. It is hoped that children in Australia whose cancer has returned will also get the chance to take part in the first trial of the new drug in infants next year.

According to the researchers, CBL0137 works by trapping the protein FACT onto chromatin, which in turn reactivates the p53 pathway and induces an interferon response.

Writing in the International Journal of Cancer, lead author Dr Klaartje Somers said that, by itself, the drug delayed the progression of  leukaemia in mouse models, but when it was combined it with chemotherapy it worked even better.

For the study, mice were injected with leukaemia cell lines, or bone marrow samples from patients who had untreatable cancers.

When the team used CBL0137 or the chemotherapy treatments by themselves there was either no response or only a partial response. However, when the treatments were combined, a complete response was observed, and often maintained. The combination extended event-free survival in all mice, compare to placebo.

Dr Somers hopes the new combination therapy will help to reduce the amount of chemotherapy that patients require and reduce side effects.

She said: “Survival rates of infants suffering from this disease have not increased in decades. MLL-r leukaemia occurs as many different subtypes, depending on the particular chromosomal rearrangement in each patient’s cells. And it is thought that this makes it difficult to identify one therapeutic approach that benefits all patients.

“CBL0137 however was effective against all the different MLL-r leukaemia cells we tested and enhanced the effects of chemotherapies against those cells that were highly resistant to currently used therapies.

“In light of this result, we think that CBL0137 is a compelling compound warranting further investigation as a candidate drug in the treatment of MLL-r leukaemia.”


Source: Somers, K., Kosciolek, A., Bongers, A., El-Ayoubi, A., Karsa, M., Mayoh, C., Wadham, C., Middlemiss, S., Neznanov, N., Kees, U.R., Lock, R.B., Gudkov, A.V., Sutton, R., Gurova, K., Haber, M., Norris, M.D., Henderson, M.J. (2019) “Potent anti-leukemic activity of curaxin CBL0137 against MLL-rearranged leukemia”, International Journal of Cancer, available from doi: 10.1002/ijc.32582

 

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