Pembrolizumab in Combination With R-ICE Chemotherapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma

Exclusion Criteria

• •Previous lymphoma cancer treatment beyond third line
• •Radiotherapy or cytotoxic drugs within two weeks of trial treatment
• •Major surgery within 4 weeks of trial registration. If a subject had major surgery, more than 4 weeks ago, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
• •Treatment with any unlicensed drug within 4 weeks of trial treatment
• •History of stroke or intracranial haemorrhage within 6 months prior to registration
• •Pre-existing peripheral neuropathy grade \>2
• •Clinically significant cardiac disease (inc. unstable angina, acute myocardial infarction, congestive heart failure, a current LVEF of \<40%) within 6 months of registration
• •Any significant uncontrolled medical condition or known hypersensitivity to the study drugs
• •Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis and tuberculosis.
• •Other past or current malignancy within 2 years prior to registration unless in the opinion of the investigator it does not contraindicate participation in the study. Subjects who have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma, are eligible
• •Known CNS involvement
• •Serological positivity for Hepatitis B, C, or known HIV infection. As per standard of care, prior to initiation of immunochemotherapy, the results of hepatitis serology should be known prior to commencement of therapy.
• •Positive test results for chronic HBV infection (defined as positive HBsAg serology) will not be eligible.
• •Patients with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) will not be eligible.
• •Patients who have protective titres of hepatitis B surface antibody (HBsAb) after vaccination will be eligible.
• •Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
• •Screening laboratory values :
• •* platelets \<75x109/L (unless due to lymphoma involvement of the bone marrow)
• •* neutrophils \<1.0x109/L (unless due to lymphoma involvement of the bone marrow)
• •* creatinine \>2.0 times upper normal limit (unless due to lymphoma or unless creatinine clearance \>50mL/min)
• •* total bilirubin \>1.5 times upper normal limit (unless due to lymphoma or a known history of Gilbert's disease)
• •* ALT/AST \>2.5 times upper normal limit (unless due to lymphoma)
• •* alkaline phosphatase \>2.5 times upper normal limit (unless due to lymphoma)
• •History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis (Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone will be eligible as will be patients with controlled Type I diabetes mellitus on a stable dose of insulin).
• •Patients who have previously undergone allogeneic transplantation.
• •Live vaccination within 28 days of study treatment.
• •Pregnant or lactating females. Women of child-bearing potential should have negative pregnancy test.
• •History of severe allergic anaphylactic reactions to chimeric, human or humanised antibodies, or fusion proteins.
• •History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• •Known hypersensitivity to CHO cell products or any component of the pembrolizumab formulation.
• •Previous treatment with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• •Corticosteroid use \>10 mg/day of prednisolone or equivalent, for purposes other than for lymphoma symptom control.
• •Patients receiving corticosteroid treatment with \<10 mg/day of prednisolone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to the start of Cycle 1. If glucocorticoid treatment is urgently required for lymphoma symptom control prior to the start of study treatment, prednisolone 100 mg or equivalent could be given for a maximum of 14 days as a pre-phase. A dose of up to 10mg or prednisolone or equivalent may be used during the screening phase to control symptoms.