Diffuse large B-cell lymphoma Cancer Diffuse large B-cell lymphoma
Conditions
Interventions
This research study is designed to see if adding polatuzumab vedotin to standard anti-cancer drugs (rituximab, gemcitabine, prednisolone or rituximab, doxorubicin, cyclophosphamide and prednisolone) m
Sponsors
Clatterbridge Cancer Centre NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female subjects =16 years of age at the time of enrolment 2. Ability to understand and sign written informed consent 3. Adequate contraceptive precautions if relevant 4. No active malignant disease other than non-melanotic skin cancer or carcinoma in situ of the uterine cervix in the last 3 years 5. ECOG performance status 0-2, at the time of screening 6. Measurable disease 7. Previously untreated histologically proven CD20 and CD79b +ve Diffuse large B cell non-Hodgkin’s lymphoma (DLBCL) according to the current World Health Organisation 2016 classification including all morphological variants: 7.1. DLBCL, not otherwise specified (NOS) including GCB and ABC 7.2. T-cell/histiocyte rich large B lymphoma 7.3. Epstein Barr virus positive DLBCL NOS 7.4. ALK-positive large B cell lymphoma 7.5. HHV8 positive DLBCL, NOS 7.6. High-grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double hit or triple hit lymphoma) 7.7. High-grade B cell lymphoma, NOS 8. The B-cell nature of the proliferation must be verified by the positivity with anti-CD20 and anti-CD79b antibodies before entry to the study. A central pathology panel will review all histology 9. At least one bi-dimensionally measurable lesion, defined as >1.5 cm in its longest dimension as measured by CT or MRI 10. Availability of archival or freshly obtained tumour tissue 11. No previous chemotherapy, radiotherapy, or other investigational drug for this indication 12. Patients with a cardiac status that does not allow the administration of 6 courses of R-CHOP as defined by an ejection fraction of 50% but there is evidence of other significant co-morbid cardiac risk factors (i.e. Hypertension, Diabetes Mellitus, previous history of Ischaemic heart disease, previous cardiac dysfunction, renal impairment etc.) that may preclude full dose anthracycline use, these patients may be considered for trial entry 13. Adequate bone marrow function as defined by: 14. Platelets >100 x 10e9 /l; WBC >3 x 109 /l; neutrophils >1.0 x 10e9 /l at the time of study entry - unless attributed to bone marrow infiltration by lymphoma 15. Serum bilirubin 30 ml/min as assessed by urinary creatinine clearance or Cockcroft-Gault Formula 17. No concurrent uncontrolled medical condition 18. Life expectancy >3 months 19. Bulky stage IA (defined as lymph node or lymph node mass greater than 10 cm in diameter), stage IB, stage II, stage III and stage IV 20. Patients receiving corticosteroid treatment with =20 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 21. If glucocorticoid treatment is urgently required for lymphoma symptom control prior to the start of treatment, prednisolone 1 mg/kg or equivalent is permitted to a maximum of 14 days as a pre-phase treatment
Exclusion criteria
Exclusion criteria: 1. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products 2. Patients with central nervous system or meningeal involvement by the lymphoma 3. Contraindication to any of the individual components of mini-CHP or GCP including prior administration of anthracyclines. 4. Prior organ transplantation 5. Demyelinating Charcot-Marie-Tooth disease 6. Burkitt lymphoma 7. Primary mediastinal B-cell lymphoma 8. Prior treatment with cytotoxic drugs within 5 years of screening for any condition (e.g. cancer, rheumatoid arthritis) or prior use of any anti-CD20 antibody. 9. Patients with a previous diagnosis of low-grade lymphoma (NB: a concurrent finding of low-grade NHL in the BM at presentation is allowed) and patients with non-bulky stage IA disease 10. Patients with positive serology for HIV, HTVL-1, HCV, HepBcAb, HepBsAg 11. Patients with suspected active Tuberculosis or latent Tuberculosis 12. Pregnancy or lactation or intending to become pregnant during the study 13. Peripheral neuropathy >Grade 1 14. Known active bacterial, viral, fungal or parasitic infections 15. Illicit drug or alcohol abuse; active viral or other hepatitis or cirrhosis 16. Prolonged corticosteroid use >20 mg/day of prednisolone or equivalent for purposes other than lymphoma symptom control
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival defined as disease progression or recurrence, or death from any cause, (defined as days from the date of cohort assignment to event) occurring within 12 months as assessed by the investigator using the revised Lugano response criteria for malignant lymphoma | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The frequency of Grade 3-4 adverse events (AEs) will be assessed according to standard National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 following each cycle of treatment and at each subsequent follow-up visit until 12 months after the last dose of treatment 2. The number of patients completing the 6 planned courses of therapy in each cohort, recorded on treatment forms for each of the 6 planned courses of therapy 3. Investigator-assessed end-of-treatment FDG-PET-CT scan assessed using the revised Lugano response criteria for malignant lymphoma (2016) at the end of treatment 4. Overall survival measured as the time from recruitment until death by any cause 5. Time to next treatment recorded on an additional treatment form throughout study participation 6. Quality of life measured using the EQ-5D patient completed questionnaire pre- and post-treatment and at every 3 monthly follow-up visit 7. Co-morbidity/frailty assessed using echocardiography or nuclear medicine examination [MUGA] pre- and post-treatment (excluding haematological comorbidities) | — |
Countries
England, Scotland, United Kingdom
Outcome results
None listed