Clinical research on haematological and MPN cancer

The investigation of haematological malignancies (cancers of the blood, bone marrow and lymph nodes) represents a significant area of clinical and research activity. Our understanding of how and why blood cancers develop is underpinned by basic research into how blood cells develop normally and what happens at the earliest stage of malignancy. Research is closely aligned with clinical treatment so that patients receive the best diagnostic and therapeutic options based on their particular cancer.

Leukemia trial – JAK2
This trial identified a single point mutation in JAK2 in many patients with myeloproliferative neoplasms, and validated a molecular diagnostic test, which is the first screening test to be introduced worldwide.

A trial testing new drug combinations
A large clinical trial of over 1,000 patients with a myeloproliferative disorder called essential thrombocythaemia is taking place to assess the efficiency of different combinations of drug treatment.

Integrating the lab and the clinic
Myeloproliferative disorders are a group of diseases in which the bone marrow makes too many red blood cells, white blood cells, or platelets. Researchers have discovered that many people with these disorders have a particular genetic mutation affecting an enzyme, called JAK2. This enzyme has an important role for carrying messages within cells but, in the case of these disorders, the mutation causes too many new blood cells to be produced. The finding means that patients can be offered different treatment depending on whether or not their disease has been caused by the mutation.

Current open trials in Cambridge

The table below lists current open trials for MPN cancer coordinated by the Cambridge Cancer Trials Centre (last updated January 2016).

Trial name Trial description Contact
MAJIC A RandoMised study of best Available therapy versus JAK Inhibition in patients with high risk Polycythaemia Vera or Essential Thrombocythaemia who are resistant or intolerant to HydroxyCarbamide Dr Anna Godfrey
The Causes of Clonal Blood Cell Disorders The Causes of Clonal Blood Cell Disorders Prof Tony Green

The table below lists current open trials for haematological cancer coordinated by the Cambridge Cancer Trials Centre (last updated January 2016).

Trial name Trial description Contact

AML19 will build upon the results of previous trials in acute myeloid leukaemia. It will evaluate several relevant therapeutic questions in patients who are 18-60 years old and suitable for intensive chemotherapy. For patients who do not have the APL subtype, the investigators will evaluate the best way of adding mylotarg to induction chemotherapy.
After induction, patients will be characterised based upon their prognosis and may enter different randomisations the randomisations allow patients to access different treatments based on their disease profile. The investigators will also evaluate whether continued monitoring of patients can improve outcomes and affects quality of life. Patients with the
APL subtype will enter a different part of the trial.

Dr Jenny Craig 

The AML18 Trial will evaluate several therapeutic questions in Acute Myleoid Leukaemia (AML). The trial will recruit 1600 patients primarily over the age of 60 who are considered fit for an intensive approach to treatment.
A randomisation will compare standard chemotherapy schedule Daunorubicin/AraC( DA) combined with 1 or 2 doses of Mylotarg in course 1, patients who fail to achieve CR or are MRD positive after course 1 will be randomised to compare DA with DA plus Cladribine or FlagIda for up to 2 courses of therapy.
Patients who achieve CR after course 1 will be randomised to 1 or 2 further courses of DA. At course 2 patients will also be randomised to receive AC220 versus no AC220 with or without maintenance, or Ganetespib verses no Ganetespib for a maximum of 3 cycles.

Dr Jenny Craig
CANC - 3935 VELCADE Melphalan-Prednisone (VMP) vs Daratumumab with VMP (D-VMP) in Myeloma A Phase 3, Randomised, Controlled, Open-label Study of VELCADE (Bortezomib) Melphalan-Prednisone (VMP) Compared to Daratumumab in Combination with VMP (D-VMP), in Subjects with Previously Untreated Multiple Myeloma who are Ineligible for High-dose Therapy Dr Charles Crawley
CANC - 3948 SADAL A Phase 2b Openlabel, Randomized Two-arm Study of Selinexor (KPT330) with Low Dose Dexamethasone in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Dr George Follows
Figaro A Randomised Trial of the FLAMSA-BU Conditioning Regimen in Patients with Acute Myeloid Leukaemia and Myelodysplasia Undergoing Allogeneic Stem Cell Transplantation Dr Charles Crawley
FLAIR: Front-Line therapy in CLL: Assessment of Ibrutinib + Rituximab Front-Line therapy in CLL: Assessment of Ibrutinib + Rituximab Dr George Follows
I-BET A phase I/II open-label, dose escalation study to investigate the safety, pharmacokinetics, pharmacodynamics and clinical activity of GSK525762 in subjects with relapsed, refractory hematologic malignancies Dr Brian Huntly
LI-1 Leukaemia Lymphoma Research and NCRI Working Group Pick a Winner Programme (LI1) Trial Dr Jenny Craig
MDS REGISTRY A prospective, multicenter European Registry for newly diagnosed patients with Myelodysplastic Syndromes of IPSS low and intermediate-1 subtypes. Dr Jenny Craig 
MUK five A phase II randomised trial of carfilzomib, cyclophosphamide and dexamethasone (CCD) vs cyclophosphamide, velcade and dexamethasone (CVD) for first relapse or primary refractory multiple myeloma. Dr Charles Crawley
NCRN508 ECHELON-2 - brentuximab vedotin and CHP (A+CHP) VS CHOP in  T-cell lymphomas A randomized, double-blind, placebo-controlled, phase 3 study of brentuximab vedotin and CHP (A+CHP) versus CHOP in the frontline treatment of patients with CD30-positive mature T-cell lymphomas Dr Ben Uttenthal
NCRN525 (AZACITIDINE + BSC v PLACEBO + BSC) A phase 3, multicenter, randomized, doubleblind study to compare the efficacy and safety of oral azacitidine plus best supportive care versus placebo plus best supportive care in subjects with red blood cell transfusion-dependent anemia and thrombocytopenia due to ipss lower-risk myelodysplastic syndromes Dr Theodora Foukaneli
PACIFICO Alkylator Combination In Follicular lymphoma Immuno-Chemotherapy for Older patients: a phase III comparison of first-line R-CVP versus R-FC (previous acronym:  RiCH FLO) Dr George Follows
PROmPT Platelet Responsiveness and Outcome from Platelet Transfusion PROmPT  Platelet Responsiveness and Outcome from Platelet Transfusion  Does inherent variation in donor platelet function affect the clinical efficacy of apheresis platelets? A randomised double blind single centre trial Dr Theodora Foukaneli
ProT4 (Prophylactic Transfer of CD4 Lymphocytes) Multicentre randomised phase II study to evaluate the efficacy of prophylactic transfer of CD4 lymphocytes after T-cell depleted reduced intensity HLA-identical sibling transplantation for indolent non-Hodgkin's lymphoma and CLL Dr Charles Crawley
UK Haplo

Stem cell transplantation has been used for many years in the treatment of cancers that affect the blood, bone marrow and lymphatic system. Most transplants use blood forming cells (‘stem cells’). If the patient’s own cells are infused, this is called an ‘autologous transplant’, and if cells are from another person, this is called an ‘allogeneic transplant’.
The stem cells can take the form of either bone marrow or stem cells harvested from the donor’s blood using a process called ‘apheresis’, whereby blood is taken from the donor and passed through a cell separating machine which takes out the cells we want to use – the rest of the blood is returned to the donor’s body. In most allogeneic transplants, cells are donated by someone who is genetically very similar to the patient either the patient’s brother or sister (a ‘sibling donor’), or an unrelated donor identified by a process of matching through a donor registry. However, as many as 1 in 3 patients do not have a fully matched sibling or volunteer unrelated donor. There are other options for these patients, which include transplants of blood from umbilical cords, or a ‘haploidentical transplant‘ which is a ‘half matched’ transplant, and donors are usually the patient’s parents or children. Historically, haploidentical transplants have been difficult to perform as the less well matched cells cause complications such as graft versus host disease. However, researchers in the USA have recently developed new haploidentical transplantation methods with improved results. This trial will test these new techniques at a number of hospitals in the UK. Two treatments being tested an intensive ('myeloablative') transplant and a reduced intensity transplant.

The primary aim of the trial is to improve survival at one year post transplant, but the study will also look at the side effects of the transplants and quality of life.

Dr Ben Uttenthal
UKALL 14 A randomized trial for adults with newly diagnosed acute lymphoblastic leukaemia Dr Jenny Craig 
UKALL 2011 United Kingdom National Randomised Trial for Children and Young Adults with Acute Lymphoblastic Leukaemia and Lymphoma 2011 Dr Michael Gattens
Understanding and managing the coagulopathy of APL (Pilot Study) Understanding and managing the coagulopathy of Acute Promyelocytic leukaemia in the acute stage - pilot study. Dr Jenny Craig 

If you would like further information about how to take part in any of the clinical trials listed here that are open to recruitment, please talk to your cancer specialist as patients usually need to be referred by their doctor.

Cambridge Cancer Trials Centre contact for MPN cancer trials: Professor Tony Green and for haematological cancer trials: Dr George Follows