aggressive large B-cell lymphoma MedDRA version: 20.0 Level: HLT Classification code 10012819 Term: Diffuse large B-cell lymphomas System Organ Class: 100000004851
Conditions
Interventions
Trade Name: Columvi
Product Name: Glofitamab
Product Code: RO7082859
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Glofitamab
Current Sponsor code: Glofitamab
Concent
Sponsors
Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: (1) Patient has provided written informed consent and is able and willing to comply with the study protocol and protocol mandated hospitalizations according to ICH and local regulations. (2) Patient (male, female, non-binary) is a) Age > 80 years, medically fit to receive the combination therapy OR b) Age 61-80 years, medical non-fit and not eligible for R-CHOP-like therapies. (3) Patient has histologically confirmed aggressive lymphoma. Note: transformed follicular lymphoma and composite lymphoma can be included as long as the low-grade component had not obtained treatment. (4) Baseline biopsy material is available for central review. (5) Female patients considered as women of childbearing potential (WOCBP, see section 5.2.7 for definition) and male patients with female partners considered as WOCPB must a) agree to either remain completely abstinent (refrain from heterosexual intercourse) or to use at least one effective contraceptive methods that results in a failure rate of < 1% per year from screening until: o At least 4 months after last dose of glofitamab, 9 months after last dose of polatuzumab vedotin, 12 months after last dose of rituximab or 18 months after last dose of obinutuzumab, whichever is longer, if the patient is female o At least 4 months after last dose of rituximab, obinutuzumab and glofitamab or 6 months after last dose of polatuzumab vedotin, whichever is longer, if the patient is male b) refrain from donating ova (female patients) or donating sperm (male patients) during the same period as stated in a). c) in case of male patients with pregnant female partners, remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures such as a condom to avoid exposing the embryo. Female patients who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile, see section 5.2.7) as well as azoospermic male patients do not require contraception. (6) Patient did not receive any prior lymphoma therapy. Note: Except for a corticosteroid prephase. (7) Patient has a ECOG performance status of = 2. Note: Subjects with an initial ECOG performance status of 3 may be considered during screening if the performance status is DLBCL-related and if pre-phase treatment (not more than 100 mg steroids/day up to 7 days prior to Cycle 1 Day 1) during the screening phase results in an improvement of ECOG performance status to = 2 prior to enrollment. (8) Patient has a life expectancy (in the opinion of the investigator) of at least 12 weeks. (9) Patient has adequate liver function: a) Total bilirubin =1.5 x ULN (=3 x ULN in patients with Gilbert’s syndrome). b) AST (aspartate aminotransferase)/ALT (alanine aminotransferase), ALP (alkaline phosphatase) =3 x ULN. o Patients with bone marrow or liver involvement: ALP =5 x ULN. o Patients with documented liver involvement: AST and/or ALT =5 x ULN. c) Albumin = 2.5 g/dL. (10) Patient has adequate hematological function: a) Neutrophil count of =1.5 x 109 cells/L (1,500/µL). b) Platelet count of =75 x 109 cells/L (75,000/µL). c) Hemoglobin (Hb) =9.0 g/dL. Note: In case screening procedures are leading to situations that would exclude the patient from study participation (such as Hb value below entry criteria), the patient may still be enrolled into the trial after consultation with the Sponsor. d) For patients not receiving therapeutic anti-coagulation: INR or aPTT = 1.5 x ULN). (11) Patient has adequate renal function: a) Creatinine = 1.5 x ULN
Exclusion criteria
Exclusion criteria: (1) Patient with CLL, ALL; including CD20+ ALL, lymphoblastic lymphoma, Richter`s transformation, Burkitt lymphoma. (2) Patient = 60 years (3) Patient with known active infection, or reactivation of a latent infection, whether bacterial (e.g., tuberculosis), viral (including, but not limited to severe pneumonia, COVID-19, EBV, CMV, hepatitis B, hepatitis C, and HIV], fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics (for IV antibiotics this pertains to completion of last course of antibiotic treatment) within 4 weeks prior to study enrollment. (4) Patient with current > Grade 1 peripheral neuropathy. (5) Patient with history of confirmed PML. (6) Patient with history of leptomeningeal disease. (7) Patient with current or history of CNS lymphoma. (8) Patient with current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease. Exceptions are allowed fot this trial. (9) Patient with another invasive malignancy in the last 2 years (with the exception of basal cell carcinoma and tumors deemed by the Investigator to be of low likelihood for recurrence), with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate 90%), such as adequately-treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer. (10) Patient with significant or extensive history of cardiovascular disease (such as NYHA Class = II cardiac disease, [...]) or significant pulmonary disease (including obstructive pulmonary disease and history of bronchospasm). (11) Patient with active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis (see addendum for a more comprehensive list of autoimmune diseases and immune deficiencies), with exceptions. (12) Patient with uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). (13) Patient with history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic. (14) Patient received treatment with any other standard anti-cancer radiotherapy/chemotherapy including investigational therapy (defined as treatment for which there is currently no regulatory authority approved indication) within 4 weeks or five times the elimination half-life of the product, whichever is longer, prior to study enrollment. (15) Patient with prior solid organ transplantation. (16) Patient with prior allogeneic stem cell transplantation. (17) Patient with prior treatment with targeted therapies (e.g., tyrosine kinase inhibitors,[...]) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to study enrollment. (18) Patient with toxicities from prior anti-cancer therapy including immunotherapy that did not resolve to = Grade 1 except for alopecia, endocrinopathy managed with replacement therapy and stable vitiligo. (19) Patient with any history of immune related = Grade 3 AE except for endocrinopathy managed with rep
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the trial is to evaluate an estimator of efficacy of the chemotherapy-light combination of glofitimab, polatuzumab vedotin and rituximab in patients with previously untreated aggressive large B-cell lymphoma. ;Secondary Objective: The secondary objectives of the trial are designed to i.) further characterize the outcome and ii.) to evaluate the safety and tolerability of the chemotherapy-light combination R-Pola-Glo in patients with previously untreated DLBCL.;Primary end point(s): 1 year progression-free survival (PFS) rate ;Timepoint(s) of evaluation of this end point: Analysis of the primary efficacy endpoint and the secondary endpoints will be performed following recruitment of all analyzable patients and with adequate observation time to assess the 1-years PFS rate. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): i.) Outcome-related corresponding endpoints • Event-free survival (EFS) • Overall survival (OS) • Response rates after 2 cycles (during target dose phase), 6 cycles (end of target dose phase before start of maintenance) and 12 cycles (end of treatment following completion of maintenance). i.e., complete remission rate , partial remission (PR) rate, overall remission rate (ORR: CR+PR), stable disease (SD) rate and progression disease (PD) rate • Relapse rate • Conversion rate of PRs to mCRs during target dose (C2-C6) and maintenance phase (C6-C12) • Duration of response (DoR) ii.) Safety, tolerability and protocol adherence-relpated corresponding endpoints: • Rate and type of adverse events (AEs) and serious adverse events (SAEs) • Rate of secondary malignancies • Treatment-related death rate • Protocol adherence • Patient-reported outcomes for quality of life (QoL) as measured by EORTC QLQ-C30 and FACT-Lym • Ratio and patient characterisitcs of patients in cohort I vs. cohort II ;Timepoint(s) of evaluation of this end point: The final analysis will be performed after all enrolled patients have completed the follow up and all study documentation as well as the correction of all CRFs has been completed (database lock). | — |
Countries
Germany
Contacts
Public ContactIKF
Institut für Klinische Krebsforschung IKF GmbH am Krankenhaus Nordwest
Outcome results
None listed