Diffuse large B-cell lymphoma in patients with co-morbidities who cannot tolerate full dose R-CHOP. MedDRA version: 21.0 Level: PT Classification code 10012818 Term: Diffuse large B-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Polatuzumab Vedotin
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: Polatuzumab Vedotin
Concentration uni
Sponsors
The Clatterbridge Cancer Centre NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Males and female subjects =16 years of age at the time of enrolment -Ability to understand and sign written informed consent -Adequate contraceptive precautions if relevant. -No active malignant disease other than non-melanotic skin cancer or carcinoma in situ of the uterine cervix in the last 3 years. -ECOG performance status 0-2, at the time of screening. -Measurable disease -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. o DLBCL, not otherwise specified (NOS) including GCB and ABC o T-cell / histiocyte rich large B lymphoma o Epstein Barr virus positive DLBCL NOS o ALK –positive large B cell lymphoma o HHV8 positive DLBCL, NOS o High grade B –cell lymphoma with MYC and BCL2 and / or BCL6 rearrangements (double hit or triple hit lymphoma) o High grade B cell lymphoma, NOS -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. -At least one bi-dimensionally measurable lesion, defined as >1.5 cm in its longest dimension as measured by CT or MRI -Availability of archival or freshly obtained tumour tissue -No previous chemotherapy, radiotherapy, or other investigational drug for this indication. -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% either assessed by echocardiography or nuclear medicine examination [MUGA] or New York Heart Association classification Grade III or IV. If the ejection fraction is >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. -Adequate bone marrow function as defined by: Platelets > 100x109 /l; WBC > 3 x 109 /l; Neutrophils > 1.0 x 109 /l at the time of study entry - unless attributed to bone marrow infiltration by lymphoma. Serum bilirubin 30ml/minute as assessed by urinary creatinine clearance or Cockcroft-Gault Formula. -No concurrent uncontrolled medical condition -Life expectancy > 3 months. -Bulky stage IA (defined as lymph node or lymph node mass greater than 10cm in diameter), stage IB, stage II, stage III and stage IV. -Patients receiving corticosteroid treatment with = 20mg /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 treatment, prednisolone 1 mg/
Exclusion criteria
Exclusion criteria: a. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products b. Patients with central nervous system or meningeal involvement by the lymphoma c. Contraindication to any of the individual components of mini-CHP or GCP including prior administration of anthracyclines. d. Prior organ transplantation e. Demyelinating Charcot-Marie-Tooth disease f. Burkitt lymphoma g. Primary Mediastinal B-cell Lymphoma h. 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. i. 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 j. Patients with positive serology for: HIV, HTVL-1, HCV, HepBcAb, HepBsAg k. Patients with suspected active Tuberculosis or latent Tuberculosis l. Pregnancy or lactation or intending to become pregnant during study m. Peripheral neuropathy > Grade 1 n. Known active bacterial, viral, fungal or parasitic infections o. Illicit drug or alcohol abuse; active viral or other hepatitis or cirrhosis p. Prolonged corticosteroid use > 20mg/day of prednisolone or equivalent for purposes other than lymphoma symptom control
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: The secondary research objective is to assess the safety and tolerability of POLA-R-GCP or POLA-R-mini-CHP through an analysis of the frequency of adverse events (AEs) and the number of patients who discontinue therapy due to toxicity. ;Timepoint(s) of evaluation of this end point: Occurring within 12 months (from the date of cohort assignment). ;Main Objective: The primary objective is to determine if the efficacy of polatuzumab vedotin, rituximab, gemcitabine and prednisolone (POLA-R-GCP) or polatuzumab vedotin, rituximab, doxorubicin, cyclophosphamide and prednisolone (POLA-R-mini-CHP) is sufficient for further investigation in patients not fit for full dose R-CHOP chemo-immunotherapy. ;Primary end point(s): The primary outcome is the 12-month Progression Free Survival rate which is measured as a binary covariate. Progression-free survival is defined as disease progression or recurrence, or death from any cause, (defined as days from the date of cohort assignment to event)as assessed by the investigator using the revised Lugano response criteria for malignant lymphoma (2016). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): a. Toxicity: The frequency of Grade 3-4 adverse events (AEs) - Grade 3-4 toxicities occurring anytime from the start of treatment until 12 months following the last dose of treatment. Adverse events/Toxicities 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. b. The number of patients completing the 6 planned courses of therapy in each cohort c. Investigator assessed end-of-treatment FDG-PET Response as assessed by a PET/CT scan performed at the end of treatment using the revised Lugano response criteria for malignant lymphoma (2016). d. Overall survival measured as the time from recruitment until death by any cause e. Time to next treatment f. Quality of life g. Co-morbidity/Frailty assessment pre- and post-treatment (excluding haematological co-morbidities) ; Timepoint(s) of evaluation of this end point: a. Until 12 months after the last treatment dose b. N/A c. 4-6 weeks after last course of treatment d. 12 months from the date of cohort assignment e. From date of last treatment to next treatment over a maximum of 24 months f. Pre-treatment; 4-6 weeks after last course of treatment; every 3 months for 2 years, and then every 4 months for 1 year and then every 6 months for two years g. Pre-treatment and 4-6 weeks after last course of treatment | — |
Countries
United Kingdom
Contacts
Public ContactCRUK Liverpool Cancer Trials Unit
University of Liverpool
Outcome results
None listed