The Midlands

The Midlands

We have a large programme of research based in Birmingham, Leicester and Nottingham.

Our Trials Acceleration Programme (TAP) hub and centre is based at The Queen Elizabeth Hospital in Birmingham. We also have TAP centres at The Leicester Royal Infirmary and The Nottingham City Hospital, and an affiliate centre at The University Hospitals of North Midlands in Stoke.

University of Birmingham

Our research in Birmingham is tailoring therapies for hard to treat chronic lymphoblastic leukaemia (CLL), and finding new treatments for non-Hodgkin lymphoma (NHL), acute myeloid leukaemia (AML) and myeloma. We are also conducting research and clinical trials that are looking for ways to improve the success of stem cell transplants and want to prevent complications, such as Graft versus Host Disease (GvHD). And we have a trial which is refining treatment for children who have acute lymphoblastic leukaemia (ALL) or a type of NHL called lymphoblastic lymphoma (LBL), so that there are less side effects. 

Our Trials Acceleration Programme (TAP) hub and centre is based at The Queen Elizabeth Hospital in Birmingham. A number of TAP trials are being led from here that are looking for new ways to treat people with AML and myelodysplastic syndromes (MDS), with a focus on finding treatments that are suitable for people that are unable to tolerate current treatments, and for those who have relapsed. 

Professor Tatjana Stankovic and her team want to improve the outcome of people with hard to treat CLL, by tailoring therapies for this group of people. People with CLL are usually treated with chemotherapy and monoclonal antibodies, such as rituximab. While most people do well on these types of treatments, some unfortunately do not respond, or eventually relapse. One way CLL becomes resistant to chemotherapy is through changes in the ATM and TP53 genes. In healthy cells, these genes produce proteins that check for DNA damage in the cell before it divides. In CLL cells that carry these gene changes, the proteins that check for DNA damage proteins are missing. People with these gene changes are also more likely to see their CLL return, and generally have a poorer outcome. Professor Tatjana Stankovic is analysing samples from people enrolled in clinical trials, so they can look at behaviour of blood cancers with defective ATM and TP53 cells. Researchers will also test in the laboratory individual patients’ CLL cells to determine which currently available treatment is most efficient in killing these cells.

Diffuse large B cell lymphoma (DLBCL) the common lymphoma, and is highly aggressive. This type of lymphoma is usually treated with chemotherapy together with an antibody therapy called rituximab. However, this approach does not work well for everyone, as many people do not respond, or only have a partial response. DLBCL appears to avoid immune responses directed against it, although the exact mechanisms are still unclear, so Dr Graham Taylor and his team want to find out how. Researchers hope that improving our understanding of these fundamental processes may lead to improved immune-based treatments for DLBCL that work by restoring or enhancing immune responses against the tumour.

Another lymphoma project is being led by Professor Paul Murray. The team want to find new ways to treat people with Hodgkin lymphoma, so they can improve outcomes for those who do not respond well to, or who are to tolerate conventional therapies. There is also a need to reduce the long-term side-effects of chemotherapy and radiotherapy, which can be harsh especially in children and young adults. Professor Murray and his team want to investigate how two naturally occurring small molecules called lipids can cause Hodgkin lymphoma when they are over-produced. Researchers will be testing if new drugs designed to inhibit lipids are effective in animal models of these lymphomas, and will determine if measuring lipid levels in tissues and blood helps researchers identify people who might benefit from these new therapies.

Professors Constanze Bonifer and Peter Cockerill are finding out what turns healthy blood stem cells into leukaemic stem cells. Many leukaemias are known to be sustained by transformed blood stem cells – sometimes known as ‘leukaemic stem cells’ or “cancer stem cells” - as a result of genetic changes they have acquired that permanently disrupt their normal behaviour. The team are focussing on acute myeloid leukaemia (AML) stem cells, which often have changes in important regulator genes, disrupting the blood cell production. If we can learn about the mechanisms that turn healthy blood stem cells into leukaemic cells, we may be able to reverse this process. 

We are also supporting a project that wants to improve the success of stem cell transplants. Although this treatment can cure many blood cancers, it is not always effective, and some people can relapse after the procedure. Professor Paul Moss and his team want to investigate exactly how donor immune cells recognise and kill cancer cells – a process called graft-versus-leukaemia (GvL). The team want to find ways to boost the strength of GvL, and will study how the genes of transplant donors and recipients can influence clinical outcome, so that transplant treatments can be modified to the needs of individual people.

Graft versus Host Disease (GvHD) is a complication that can arise from stem cell transplants. This is where the donor immune system recognises the normal cells of the recipient as “foreign” and attacks them, leading to organ damage. People with GvHD are usually given steroids, which dampens down the immune system. But this course of treatment does not work for everyone because some people can become dependent on steroids, or the treatment stops working. Dr Ram Malladi is leading the AZTEC trial that wants to see if using a chemotherapy called azacitidine can help people with GvHD who are dependent on steroid treatment, or who are no longer responding to steroids.

Dr Farhat Khanim is looking at repurposing existing drugs to treat myeloma. People with myeloma are usually treated with chemotherapy, which can be combined with steroids and biological therapies. But despite treatment being initially successful, in some people myeloma comes back. And because myeloma affects predominantly people over the age of 60, conventional treatments may not be suitable as the side effects can be harsh. Dr Khanim and his team are looking for treatments that have fewer side effects, but are still effective in older people and those with resistant or relapsed disease. The team have identified a combination of an anti-epileptic drug and an anti-tapeworm drug called ‘VaN’ that can kill myeloma cells in the laboratory. They now want to do further testing on this combination in the lab, with the ultimate aim of taking VaN therapy to clinical trials in older people with myeloma, and those whose disease has become resistant or has returned.

We have lots of clinical trials based at The University of Birmingham. The UKALL 2011 is being led by Professor Ajay Vora, and is looking at treatment for children who have acute lymphoblastic leukaemia (ALL) or a type of non-Hodgkin lymphoma (NHL) called lymphoblastic lymphoma (LBL). Researchers want to see if using standard drugs in slightly different ways can achieve the same results but with fewer side effects, and reduce the risk of the blood cancer from returning. 

Professor Charlies Craddock is also leading a number of TAP trials that are looking for new ways to treat people with acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). In particular we want to find treatments that are suitable for people that are unable to tolerate conventional treatments, such as intensive chemotherapy, and for those who have relapsed after stem cell transplants.

Tailoring therapies for people with treatment resistant CLL

Lead researcher - Professor Tatjana Stankovic, The University of Birmingham
Leukaemia Chronic lymphocytic leukaemia (CLL)
New approaches for tackling refractory CLL
Professor Tatjana Stankovic and her team are analysing samples from people enrolled in clinical trials, so they can look at behaviour of blood cancers with defective ATM and TP53 cells. As part of this project, researchers will also test in the laboratory individual patients’ cells to determine which currently available treatment is most efficient in eliminating these cells.

Unmasking lymphoma

Lead researcher - Dr Graham Taylor, University of Birmingham
Lymphoma High-grade non-Hodgkin lymphoma (HGNHL)
Immune control of diffuse large B-cell lymphoma (DLBCL): prospective and retrospective studies on Epstein-Barr virus-positive disease
Dr Taylor wants to find out how lymphoma appears to avoid immune responses directed against it. Improving our understanding of these fundamental processes may lead to improved treatments for DLBCL that work by restoring or enhancing immune responses against the tumour.

Finding new ways to target Hodgkin lymphoma

Lead researcher - Professor Paul Murray, University of Birmingham
Lymphoma Hodgkin lymphoma
Aberrant lysophospholipid and DDR1 signalling as therapeutic targets in Hodgkin's lymphoma and diffuse large B cell lymphoma
Professor Murray and his team are investigating how lipids can cause B cell lymphomas when they are over-produced. They will test if new drugs designed to inhibit the effects of these lipids are effective in the lab, and if measuring lipid levels in patients will help identify those who might benefit from these new therapies.

What turns healthy blood stem cells into leukaemic stem cells?

Lead researcher - Professors Constanze Bonifer and Peter Cockerill, University of Birmingham
Leukaemia Acute myeloid leukaemia (AML)
Mechanistic insights into aberrant transcriptional programming in acute myeloid leukaemia
Professors Bonifer and Cockerill are investigating the complex processes that turn healthy cells into leukaemic cells. By understanding the causes of this transformation, they hope to find ways to prevent the development of AML - and to restore healthy blood cell production.

Optimisation of the graft versus leukaemia effect to improve the outcome of haematopoietic stem cell transplantation

Lead researcher - Professor Paul Moss, University of Birmingham
Optimisation of the graft versus leukaemia effect to improve the outcome of haematopoietic stem cell transplantation
Researchers led by Professor Moss want to investigate exactly how donor immune cells recognise and kill cancer cells. The aim of this research is to find new ways to increase the strength of GvL so that transplant treatments can be modified to the needs of individual people.

Repurposing existing drugs to treat myeloma

Chief investigator - Dr Farhat Khanim, University of Birmingham
Myeloma
Preclinical testing of low dose valproate and niclosamide (VaN) as novel anti-myeloma therapy
Dr Khanim and his team are looking for kinder treatments for older people with myeloma, and for those that have become resistant to current treatments, or have relapsed disease. The team has found that a combining an epilepsy medication with an anti-tapeworm drug kills myeloma cells in the lab and they now want to test this further. If successful, they plan to take this treatment into a clinical trial in older people with myeloma, and in people with hard-to-treat disease that has become resistant or has returned.

AZTEC trial

Chief investigator - Dr Ram Malladi, University of Birmingham
A Phase II study of the use of azacitidine for the treatment of patients with chronic graft versus host disease who have failed therapy with corticosteroids
People with GvHD are usually given steroids, but this course of treatment does not work for everyone. Researchers want to see if using a chemotherapy called azacitidine can help people with GvHD who are dependent on steroid treatment, or who are no longer responding to steroids. 

UKALL 2011

Chief investigator - Professor Ajay Vora, University of Birmingham
Childhood acute lymphoblastic leukaemia (Ch-ALL)
UK Acute Lymphoblastic Leukaemia Trials
This trial is looking at treatment for children who have acute lymphoblastic leukaemia (ALL) or a type of non-Hodgkin lymphoma (NHL) called lymphoblastic lymphoma (LBL). Researchers want to see if using standard drugs in slightly different ways can achieve the same results but with fewer side effects, and reduce the risk of the blood cancer from returning. 

RAvVA trial

Chief investigator - Professor Charles Craddock, University Hospital Birmingham
Acute myeloid leukaemia (AML) Myelodysplastic syndromes (MDS)
A randomised phase II trial of 5-azacitidine versus 5-azacitidine in combination with vorinostat in patients with relapsed acute myeloid leukaemia ineligible for salvage chemotherapy
In this trial, researchers want to know if azacitidine given with vorinostat is better than azacitidine alone in people with AML or high risk MDS who are unable to tolerate intensive chemotherapy.

VIOLA trial

Chief investigator - Professor Charles Craddock, University Hospital Birmingham
Acute myeloid leukaemia (AML) Myelodysplastic syndromes (MDS)
A phase I trial of combined azacitidine and lenalidomide salvage therapy in patients with acute myeloid leukaemia who relapse after allogeneic stem cell transplantation
People with AML or MDS are usually treated with high doses of chemotherapy, followed by a stem cell transplant. But AML and MDS can come back after a transplant, and when it does it becomes much more difficult to treat. Researchers want to know if combining azacitidine and lenalidomide can help this group of people.

ROMAZA trial

Chief investigator - Professor Charles Craddock, University Hospital Birmingham
Acute myeloid leukaemia (AML)
Phase I trial of romidepsin plus azacitidine in patients with newly diagnosed, relapsed or refractory acute myeloid leukaemia ineligible for conventional chemotherapy
People with AML are usually given chemotherapy, but not everyone can have this type of treatment. Researchers think that combining azacitidine with romidepsin may help people with AML who can’t have standard chemotherapy treatment.

FIGARO trial

Chief investigator - Professor Charles Craddock, University Hospital Birmingham
Acute myeloid leukaemia (AML) Myelodysplastic syndromes (MDS)
A randomised trial of the FLAMSA-BU conditioning regimen in patients with acute myeloid leukaemia and myelodysplasia undergoing allogeneic stem cell transplantation
This trial is looking at a reduced intensity conditioning regimen called FLAMSA-BU. Researchers think that this treatment could improve outcomes in older people because of reduced side effects and a lower risk of AML or MDS returning. FLAMSA-BU will be compared with standard intensity conditioning.

University of Leicester

We have two lymphoma projects at the University of Leicester – a Trials Acceleration Programme (TAP) trial that is looking at a new treatment for peripheral T-cell lymphoma (PTCL), and research that could lead to new treatments for people with resistant diffuse large B cell lymphoma (DLBCL). Peripheral T-cell lymphoma (PTCL) is an aggressive and difficult to treat non-Hodgkin’s lymphoma that has relatively poor outcomes. People with PTCL are usually given a combination of chemotherapy drugs. But for people who relapse after this course of treatment, there are limited treatment options available. Professor Simon Wagner is leading the AVAIL-T trial, to see if an antibody therapy called avelumab could be an effective addition to treatments for PTCL. Avelumab is an antibody therapy that targets cells that have a molecule called PD-L1 on their surface, which includes lymphoma cells. Researchers hope that avelumab may help people with PTCL who have not responded to initial treatment, or have relapsed. Our other project here is developing new treatment avenues for people with non-Hodgkin lymphoma (NHL), and is being led by Professor Anne Willis who is based at the MRC Toxicology Unit in Leicester, alongside Dr Martin Turner at the University of Cambridge. This team have already shown that in diffuse large B-cell lymphoma (DLBCL) there is an increase in the levels of a protein called eIF4B, which is associated with a poor outcome. They now want to find new ways to inhibit the function of eIF4B, which could in the future lead to new treatment options for individuals with DLBCL that do not respond to current treatments.

University of Nottingham

We have one TAP trial that is being run from The Nottingham University Hospitals NHS Trust 

Dr Christopher Fox is running the TIER trial, which is looking for new ways to treat people with primary central nervous system lymphoma (PCNSL) - a rare type of non-Hodgkin lymphoma that only affects the central nervous system. People with PCNSL are usually treated with chemotherapy. But sometimes the lymphoma does not respond to chemotherapy, or it comes back after treatment. In this situation there is no standard treatment, so we need to find new ways to treat this group of people. This trial will test a new combination of cancer drugs comprising of chemotherapies and a biologic drug.

TIER trial

Chief investigator - Dr Christopher Fox, Nottingham University Hospitals NHS Trust
Diffuse large B cell lymphoma (DLBCL)
A phase I/II study of thiotepa, ifosphamide, etoposide and rituximab for the treatment of relapsed and refractory primary central nervous system lymphoma
Researchers are looking for new ways to treat people with PCNSL - a rare type of non-Hodgkin lymphoma that only affects the central nervous system. The trial is trying a new combination of cancer drugs comprising of chemotherapies and a biologic drug. 

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