Treatment of Patients With Diffuse Large B Cell Lymphoma Who Are Not Suitable for Anthracycline Containing Chemotherapy (INCA)

This is an interventional treatment trial for Diffuse Large B Cell Lymphoma focused on measuring Diffuse large b cell lymphoma, Inotuzumab Ozogamicin, Gemcitabine, Rituximab, Cyclophosphamide, Vincristine, Prednisolone Read More

Inclusion criteria:

• Informed written consent for the trial
• Histologically proven diffuse large B cell lymphoma (DLBCL) according to the current World Health Organisation (WHO) classification including all morphological variants. The B cell nature of the proliferation must be verified by demonstration of CD20 positivity. A concurrent (synchronous) diagnosis of low grade lymphoma (e.g. on bone marrow trephine or presence of both low grade and DLBCL in a lymph node biopsy) or previous diagnosis of low grade lymphoma which hasn't been treated with a systemic therapy is permitted
• Bulky Stage IA (lymph node or lymph node mass ≥ 10cm in maximum diameter), stage IB, stage II, stage III and stage IV disease
• ECOG performance status 0-2
• Measurable disease
• Age 18 ≥ years
• Adequate contraceptive precautions for all patients of childbearing potential
• History of malignant disease diagnosed at any time in the past with completed radical treatment and the risk of relapsing within the next 5 years is <10%. Patients previously treated should be free of sequelae of treatment which would compromise the delivery of study drugs as compared with other eligible patients.
• No previous chemotherapy, radiotherapy or other investigational drug for this indication - previous corticosteroids up to a dose equivalent to prednisolone 1mg/kg/day for up to 14 days are permitted prior to randomisation EITHER
• Unsuitable for anthracycline-containing chemotherapy due to impaired cardiac function defined by an ejection fraction of ≤ 50% OR Left ventricle ejection fraction > 50% but in the presence of significant co-morbidities (diabetes mellitus, hypertension or ischaemic heart disease) precluding anthracycline-containing chemotherapy as determined by treating physician. Co-morbidities must be documented on the randomisation form and CIRS score recorded
• Adequate bone marrow function (Platelets > 100x109/l, WBC > 3.0x109/l, Neutrophils > 1.5x109/l) at time of study entry unless attributed to bone marrow infiltration by DLBCL
• Life expectancy > 3 months

Exclusion criteria:

• Symptomatic central nervous system or meningeal involvement by DLBCL
• Previous diagnosis of low grade lymphoma which has been treated with a systemic therapy
• Non-bulky stage IA disease
• ECOG performance status 3-4
• History of chronic liver disease or suspected alcohol abuse
• Serum bilirubin greater than upper limit of normal unless attributable to Gilberts syndrome or haemolysis
• Alanine and/or aspartate aminotransferase levels (ALT and/or AST) and alkaline phosphatase (ALP) greater than 2.5 times the upper limit of normal
• Glomerular filtration rate (GFR) < 30ml/min. GFR calculated by Cockroft-Gault (not eGFR).
• Serological evidence of active hepatitis B or C infection whether acute or chronic (defined as positive anti-HCV serology; positive HBsAg). All positive HBcAb results should also be excluded on safety grounds regardless of HBsAg or HBV DNA status. Antibodies to Hepatitis B surface antigen (anti-HBs) due to a history of past vaccination is acceptable
• Known history of HIV seropositive status
• Patients with a history of Venoocclusive Disease (VOD) and Sinusoidal Obstructive Syndrome (SOS)
• Patients with a screening of QTcF interval >470msec
• Medical or psychiatric conditions compromising the patient's ability to give informed consent
• Women who are pregnant or lactating
• LVEF > 50% in the absence of significant co-morbidities that preclude anthracycline use
• Patients with a history of severe allergic/anaphylactic reaction to any humanised monoclonal antibody
• Patients with serious active infection