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New drug combination for leukaemia shows highly promising results in clinical trial

The Bloodwise logo. Bloodwise appears in black text against a white background
Posted by
11 Dec 2017

Results of a UK clinical trial suggest a combination of two targeted drugs could be highly effective in treating chronic lymphocytic leukaemia

A scientist pictured in a laboratory holding a pipette

Early clinical trial results have shown that a combination of two targeted drugs could be a highly effective way to treat people who have relapsed or not responded to other treatments for the most common form of leukaemia.

All people with chronic lymphocytic leukaemia (CLL) had responded to treatment with venetoclax with ibrutinib after just six months of treatment. Response rates after six months of treatment have exceeded what doctors had expected to see after a year of treatment.

CLL is diagnosed in over 4,000 people each year in the UK and is the most common type of adult leukaemia. Patients produce immature versions of lymphocytes, a type of white blood cell, which build up in the bone marrow and crowd out healthy blood cells.

While it is not currently considered curable, treatment options for CLL have improved remarkably, and there are now lots of new targeted treatments that are being looked into that can lead to years of remission in patients.

The CLARITY study was led by Professor Peter Hillmen at St James’s University Hospital, part of Leeds Teaching Hospitals NHS Trust, and funded by the blood cancer research charity Bloodwise. It set out to establish if combining two targeted drugs, venetoclax and ibrutinib, could potentially be a safe and effective treatment.

The results were announced at the Annual Meeting of the American Society of Hematology in Atlanta on Sunday 10 December.

The trial is taking place at hospitals across the UK involved in our Trials Acceleration Programme network, organised from a central hub at the University of Birmingham. 50 people with CLL who had either relapsed or had not responded to previous treatment were recruited to the trial between May 2016 and July 2017.

Ibrutinib is a type of drug called a Bruton tyrosine kinase inhibitor, which works by targeting and switching off a protein linked to cell growth and movement in the cancer cells. Venetoclax is also a highly targeted drug, but works in a different way to ibrutinib, in that it switches off proteins on cancer cells that help keep the cells alive.

So far the treatment has been shown to be safe, with no unexpected adverse reactions experienced by patients. 49 patients have begun the drug combination treatment and 38 patients have reached six months of combination treatment. Every patient who has reached six months of treatment has responded to the drug combination, and almost a half of these patients are in complete remission.

Three in 10 patients had no detectable sign of minimal residual disease (MRD) in their bone marrow or blood after only six months of treatment. The eradication of MRD, defined as less than one leukaemia cell per 10,000 white blood cells, is known to be vital if patients are to have a long lasting period of remission.  

Professor Peter Hillmen, who is running the trial at the Leeds Cancer Centre, said:   “These early results show that combining ibrutinib with venetoclax could offer an effective alternative to chemotherapy, which has its limitations. The drug combination resulted in a significant proportion of patients going into remission after a short amount of time, offering the possibility of stopping therapy after a relatively short treatment period. The response rates we have seen in patients after just six months of treatment have far exceeded what we would have expected, so these results are really encouraging.

“The CLARITY Trial has moved from concept to meaningful results extremely rapidly demonstrating the importance of the Bloodwise TAP initiative in enabling the UK to remain at the forefront in the development of new therapies for CLL and other blood cancers.”

Dr Alasdair Rankin, Director of Research at Bloodwise, said: “A number of exciting new drugs are becoming available for people with CLL but these treatments will not work in all cases and response rates can vary. The key is determining the right drugs for the right patients and in the right combinations.

“Further monitoring time will be needed to show if these highly promising early response rates to venetoclax and ibrutinib can lead to long lasting remission in patients. It is vital that we continue to look for new ways to improve outcome and extend survival times, particularly for those who have stopped responding to their treatment.”

The positive early results from the CLARITY trial mean that the researchers will test the effectiveness of the ibrutinib and venetoclax combination against conventional chemotherapy or ibrutinib alone in a clinical trial for people with CLL who have not previously received any prior treatment.

John’s story

John, 70, from Leeds, has been treated with ibrutinib and venetoclax on the CLARITY trial since late 2016.

“I’m over the moon and absolutely astounded by the results of the CLARITY trial. When I was first diagnosed with chronic lymphocytic leukaemia I was treated with three rounds of chemotherapy, but it was too aggressive and I felt I was close to death. My blood cell levels had collapsed and I had to stop treatment. I had tumours all over my body and  huge swellings in my neck.

“I agreed to go on the CLARITY trial because I felt so close to death and mainly I wanted to help with research. I never imagined it would ever have this effect, it’s been marvellous.”

When John first started treatment the dose was escalated gradually until he reached the full dose of venetoclax that he is on now. Early on he experienced tumour lysis syndrome – a serious complication caused when tumours shrink too quickly. John had to spend two nights in hospital each time the dosage increased but was eventually able to continue the escalation of treatment.

“The benefits of the trial began almost straight away. My tumours started to shrink and I gradually felt better and better. Recent scans have showed no sign of tumours left. I can take the ibrutinib and venetoclax and the various other drugs needed at home every day. It’s so easy.  I used to have to go to sleep during the day because I was so tired and I don’t have to anymore. I can walk better, it’s made me more confident and I feel a heck of a lot better. It’s given me a whole new lease of life. Without this trial I do not think I would be here now.”