Southampton leads first national trial of chemotherapy-free treatment for rare blood cancer

Researchers in Southampton are leading a UK-wide study that aims to improve outcomes for patients with a rare blood cancer.

Around 230 people in the UK are diagnosed with Hairy Cell Leukaemia (HCL) each year. The disease affects white blood cells that are important for fighting infections.

Current treatments often involve chemotherapy. This can cause difficult side effects and does not always stop the cancer from returning.

The new study will test two tablet-based drugs. Researchers hope this approach will be more effective and less harmful than traditional chemotherapy.

The trial is led by Professor Francesco Forconi, Professor of Haematology at the University of Southampton. It is coordinated by the Southampton Clinical Trials Unit (SCTU) and sponsored by University Hospital Southampton (UHS).

The team has received $1.75m from Blood Cancer United and the Hairy Cell Leukaemia Foundation.

Patients with relapsed or refractory HCL will take part at five UK hospitals, including UHS.

What is Hairy Cell Leukaemia?

HCL is a rare type of chronic blood cancer. It is named after the hair-like growths that can be seen on the cancer cells under a microscope.

These abnormal white blood cells, called B lymphocytes, do not develop properly. They build up in the body, preventing the production of healthy white blood cells.

“While chemotherapy is often effective initially, it can have unpleasant side-effects and long‑term toxicities for patients,” says Professor Forconi.

“Many patients with Hairy Cell Leukaemia will later relapse and see the cancer come back, and at this point there are limited treatment options for them.”

Targeted chemotherapy-free treatment

Hairy Cell Leukaemia is driven by abnormal activation of B‑cell receptor signalling. It is also driven by excessive production of a protein called BCL2, which prevents cancer cells from dying.

The MAYFLOWER-HCL phase II trial will investigate a combination of two oral treatments, Zanubrutinib and Sonrotoclax. These are being provided by the company BeOne Medicines.

Together, these will target both pathways. Zanubrutinib will block signals from B‑cell receptors to stop abnormal 'hairy' B cells being made. Sonrotoclax will inhibit BCL2 to trigger cancer cell death.

The trial builds on years of laboratory and clinical research by the University’s Cancer B‑cell Group.

“This trial is designed to move the field decisively away from the more toxic chemotherapy treatments,” said Professor Forconi, “targeting instead the fundamental mechanisms that allow tumour B cells to survive.”

Southampton led UK‑wide collaboration

MAYFLOWER-HCL is the first multicentre clinical trial ever designed in the UK for Hairy Cell Leukaemia.

The trial will be coordinated by the SCTU, led by Professor Gareth Griffiths. The SCTU has world-leading expertise in blood cancer trials.

It will recruit patients across five major UK university hospitals. This will help to ensure national access for patients with this rare cancer.

“Because Hairy Cell Leukaemia is rare, large national trials are often difficult to deliver,” said Professor Griffiths.

“This award places Southampton at the centre of a UK‑wide collaborative effort, and positions the trial to influence future international treatment standards.

“It also reflects the national drive to improve treatments and survival for rare cancers, which is outlined in the new Rare Cancers Bill that recently came into UK law.

“As a leading UK trials unit, we are making sure we are playing our part in helping to accelerate this vital research in areas of unmet need for cancer patients.”

A milestone for rare cancer research

With the major funding grant secured, the trial is now being set up. It aims to open to patient recruitment by the end of the year.

“This trial is the first step in our long-term goal to provide better, kinder treatments for patients with HCL,” said Professor Forconi.

“Our hope is to not only control the disease, potentially leading to remission, but also improve patient’s quality of life while on treatment.

“This is a landmark moment for patients with Hairy Cell Leukaemia in the UK. It reflects both the strength of collaboration across NHS and academic partners, and Southampton’s growing role in leading innovative, patient‑focused cancer trials.”