Diffuse large B-cell lymphoma is the commonest type of aggressive non-Hodgkin's lymphoma, a type of cancer of a cell called a lymphocyte which makes up part of the immune system. Although most patients are cured with chemotherapy used as initial treatment, about 20-30% of patients still experience relapse. Curing relapsed disease is much less successful, even with the use of high doses of chemotherapy and stem cell transplant. There is then an urgent need for effective, new agents to treat patients with diffuse large B-cell lymphoma who have relapsed or who have developed resistance to other forms of chemotherapy.

This trial is using a drug called AZD1152 which interferes with the ability of a cancer cell to divide and grow. It has been used before in patients with other types of cancer, but never before in lymphoma patients. Responses in other cancers have been seen, particularly in leukaemia which is a disease related to lymphoma. The investigators are planning to use this agent in 15 patients with diffuse large B-cell lymphoma in which potentially curative treatments have failed. The main aim is to see whether the drug shows any activity in this type of lymphoma. This will be mainly assessed using CT and PET scans. The investigators are also investigating how well a blood test can predict both the response to the drug and the toxicity of the drug - this is called a biomarker study and forms part of the clinical trial. The other main aim of the study is to assess the toxicity of the treatment. Previous studies in humans suggest the drug is reasonably well tolerated, although side effects such as stomatitis (soreness of the mouth) and suppression of the bone marrow (leading to risk of infection and bleeding) have been seen.

Inclusion Criteria:

• Male or Female, aged ≥ 18 yrs.
• ECOG performance score of 0, 1 or 2.
• Life expectancy of at least 12 weeks.
• Haematological and biochemical indices within the ranges shown below Lab Test Value required Haemoglobin (Hb) ≥ 9g/dL White Blood Count (WBC) ≥ 2x109/L Platelet count ≥ 100x109/L Absolute Neutrophil count ≥ 1.0x109/L; Serum bilirubin ≤ 1.5 x ULN AST (SGOT) or ALT ≤ 1.5 x ULN Creatinine clearance (Cockcroft-Gault) > 50 ml/min
• Relapsed or refractory DLBCL in which all participants must have received at least one potentially curative established immunochemotherapy lymphoma regimen that contained rituximab (e.g. R-CHOP, R-PMitCEBO, R-GCVP, R-CNOP). Participants must also have failed or be ineligible for salvage/high dose therapy.
• Relapsed or refractory DLBCL proven by biopsy (within 6 months of enrolment in trial); either de novo DLBCL or transformed follicular lymphoma.
• At least 1 lesion (> 1.5cm), not previously irradiated, that can be accurately measured on CT and which is FDG avid on CT-PET scanning, as defined by Cheson criteria.
• Able to give informed consent and capable of co-operating with protocol.

Exclusion Criteria:

• Any anti-cancer therapy (including radiotherapy and participation in other clinical trials) within 28 days prior to Day 1. Patients may however be receiving corticosteroids as an anti-lymphoma treatment of 50mg daily prednisolone or equivalent up until screening. At screening (or before) this must be tapered down so that they are only on a low dose (10mg daily or less) by the time AZD1152 commences. This may be continued for indications other than lymphoma treatment throughout the study.
• Any unresolved toxicity from prior anti-cancer therapy greater than CTCAE grade I (except alopecia).
• Previous treatment with aurora kinase inhibitors.
• Clinical evidence of central nervous system involvement.
• Another active malignancy within the past five years, except adequately treated basal or squamous cell carcinoma of the skin, or carcinoma of the cervix in situ.
• Clinically significant and uncontrolled major medical condition(s) including but not limited to: active infection, bleeding diathesis, symptomatic congestive heart failure, cardiac arrhythmia or psychiatric illness/social situations which would limit compliance with protocol requirements.
• Major surgery within 4 weeks prior to entry into the study (excluding placement of vascular access or biopsy) that involved general anaesthesia or respiratory assistance.
• Mean QTc interval > 470 ms calculated from 3 ECGs using Fridericia's or Bazett's correction on 12-lead ECG machine.
• Serologically positive for HIV, hepatitis B or C assessed within 28 days of initiation of study treatment using an ELISA method performed by an HPA accredited laboratory.
• Participants of reproductive potential not willing to use adequate contraceptive measures for the duration of the study (both male and female participants).
• Pregnant or breastfeeding women. Female participants must have a negative urinary or serum pregnancy test when done or have evidence of post-menopausal status (Defined as absence of menstruation for greater than 12 months, bilateral oophorectomy or hysterectomy).
• Participants who have had live attenuated or yellow fever vaccines within 6 months of trial beginning.
• Participants not willing and able to comply with the protocol for the duration of the study, and scheduled follow-up visits and examinations.