AZD1152 in Diffuse Large B-cell Lymphoma

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.