Patients who received CAR T-cells therapy for R/R DLBCL (cohort 1) or R/R PMBL, mantle cell lymphoma, t-iNHL or iNHL (cohort 2), at least 1 month ago MedDRA version: 21.0 Level: PT Classification code 10012822 Term: Diffuse large B-cell lymphoma refractory System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10012821 Term: Diffuse large B-cell lymphoma recurrent System Organ Class: 10029104 - Neopl
Conditions
Interventions
Trade Name: GAZYVARO
Product Name: obinutuzumab
Product Code: GA101
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: OBINUTUZUMAB
CAS Number: 949142-50-1
Other descripti
Sponsors
LYSARC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients meeting all of the following criteria will be considered for enrollment into the study: 1. Patients who received CAR T-cells therapy for R/R DLBCL (cohort 1) or R/R PMBL, mantle cell lymphoma, t-iNHL or iNHL (cohort 2), at least 1 month ago 2. Patients who are not at least in partial metabolic response from 1 month after CAR T-cells infusion (i.e no metabolic response or first metabolic progressive disease or first relapse from 1 month after CAR T-cells infusion) 3. First metabolic progression, first relapse or no metabolic response after CAR T-cells infusion must be confirmed by PET-CT central review for enrollment 4. DLBCL with demonstrated lymphoma cells-expressing CD20 at relapse post CAR T-cells as demonstrated by biopsy before inclusion (cohort 1 only) 5. Aged 18 years or more with no upper age limit 6. ECOG performance status 0 or 1 7. Bi-dimensionally measurable disease defined by at least one single node or tumor lesion > 1.5 cm assessed by CT scan, or PET-CT with at least one hypermetabolic lesion 8. No persistant CAR-T neurotoxicity symptoms or previous experience during CAR T-cells therapy of neurotoxicity grade > 3 9. Adverse events from prior anti-cancer therapy must have resolved to Grade = 1 (hematological toxicities excepted). 10. Adequate liver function: Total bilirubin = 1.5 x ULN; Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) = 3 x ULN. Note: Patients with documented history of Gilbert’s Syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible) 11. Adequate hematological function: Neutrophil count of = 1.0 G/L; Platelet count of = 50 G/L (and platelet transfusion free within 14 days prior to administration of obinutuzumab); Hemoglobin (Hb) = 8.0 g/dL (transfusion free within 21 days prior to administration of obinutuzumab). Note: patients who do not meet the above hematologic criteria, due to extensive tumor involvement in the marrow may be enrolled into the trial after the demonstration of involvement and consultation with the LYSARC. Please consult the LYSARC on the need for transfusion support within 21 days of obinutuzumab. 12. Adequate renal function: creatinine clearance (CrCl) calculated by MDRD/Cockroft-Gault formula of = 30 mL/min 13. Negative serum or urinary pregnancy test within 7 days prior to study treatment in women of childbearing potential. 14. Negative serologic or PCR test results for acute or chronic HBV infection. Note: Patients whose HBV infection status cannot be determined by serologic test results must be negative for HBV by PCR to be eligible for study participation. 15. Negative test results for HCV and HIV. Note: Patients who are positive for HCV antibody must be negative for HCV by PCR to be eligible for study participation. 16. Patients must agree to either remain completely abstinent or to use two effective contraceptive methods until : - If the patient is a male: at least 3 months after pre-treatment with obinutuzumab or 2 months after the last dose of glofitamab Men must refrain from donating sperm during this same period - If patient is a female of childbearing potential: until at least 18 months after pre-treatment with obinutuzumab or 2 months after the last dose of glofitamab 17. Patient must be willing and able to comply with protocol-mandated hospitalization upon administration of the first dose of glofitamab. Patient must also be willing to comply with all study-related procedures. 18. Signed w
Exclusion criteria
Exclusion criteria: Patients meeting any of the following criteria will not be included in the study: 1. Previously known CD20 negative status, excepted if a new biopsy for cohort 1 or biopsy or cytometry analysis for cohort 2 proving a CD20 positive status is available before enrollment 2. Patients with CLL, Richter and Burkitt lymphoma. 3. Patients relapsing or progressing within 1 months (30 days) after CAR T-cells therapy 4. History of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents, as follows: - Grade = 3 adverse events with the exception of Grade 3 endocrinopathy managed with replacement therapy - Grade 1-2 adverse events that did not resolve to baseline after treatment discontinuation 5. Current or past history of detectable cerebrospinal fluid lymphoma cells, or with a history of CNS lymphoma localization or primary CNS lymphoma. 6. Current or past history of cerebral disorders 7. Any serious psychiatric illness that would prevent the subject from signing the informed consent form 8. Patients with history of macrophage activation syndrome (MAS)/hemophagocytic lymphohistiocytosis (HLH) 9. Patients with known acute infection or reactivation of a latent infection, whether bacterial, viral (including, but not limited to, EBV, cytomegalovirus (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) in 2 week prior to enrollment. 10. LVEF < 40% as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan or significant cardiovascular disease such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) 11. Any serious active disease or co-morbid medical condition 12. Clinically significant history of liver disease or cirrhosis 13. Prior history of malignancies other than lymphoma unless the subject has been free of the disease for = 3 years. Exceptions will be allowed for patients with non-melanoma skin tumors (basal cell or squamous cell carcinoma of the skin) or any surgically removed stage 0 (in situ) carcinoma 14. Prior solid organ transplantation. 15. Prior allogeneic SCT 16. Autologous SCT within 100 days prior to obinutuzumab infusion. 17. Current uncontrolled autoimmune disease Note: History of automimmune disease currently controlled and stable is acceptable for such therapy. See detailed description in paragraphe 8.2 18. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug. 19. Major surgery or significant traumatic injury < 28 days prior to the obinutuzumab infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment. 20. Administration of a live, attenuated vaccine within 4 weeks before obinutuzumab infusion 21. Treatment between infusion of the CAR T-cells and pre-phase (i.e. obinutuzumab infusion on C1/D-3): with standard radiotherapy, systemic immunotherapeutic agents, any chemotherapeutic agent, any systemic immunosuppressive medications or treatment with any other investigational anti-cancer agent (defined as treatment for
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to assess the anti-lymphoma activity of glofitamab, a bispecific CD3xCD20 monoclonal antibody in patients with relapse/refractory (R/R) DLBCL (cohort 1) disease after anti-CD19 CAR T-cells therapy.;Secondary Objective: •To evaluate safety and tolerability of glofitamab after CAR T-cells therapy failure •To assess the efficacy of glofitamab in patients in relapse/refractory after anti-CD19 CAR T-cells therapy with respect to: o Result of PET-CT at each evaluation according to local and central review o Overall Metabolic Response Rate (OMRR) o Best metabolic response and overall best metabolic response rate will be estimated at the end of treatment according to Lugano 2014 response criteria (PET-CT based) assessed by local and central review o Progression Free Survival (PFS) o Duration of Response (DoR), defined from the time of first CMR or PMR (according to Lugano criteria) •To assess disease-related symptoms, function, and health-related quality of life (HRQoL) according to the EORTC QLQ-C30 and the FACT-Lym LymS subscale.;Primary end point(s): The primary endpoint is the Overall Survival (OS).;Timepoint(s) of evaluation of this end point: Overall survival will be measured from the date of C1D1 of glofitamab to the date of death from any cause. Alive patients will be censored at the date of last contact. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints will include: • PET-CT result according to local and central review • Metabolic response rates according to Lugano classification: Response will be assessed by local and central review by PET scan according to Lugano classification (Cheson B. et al, JCO 2014) at several timepoints during study . Patients without response assessment (i.e. response not evaluated or missing) due to whatever reason will be considered as non-responders. • Progression Free Survival (PFS): PFS is defined as the time from enrollment into the study to the first observation of documented disease progression based on central review or death due to any cause. If a subject has not progressed or died, PFS will be censored at the date of tumor assessment. • Duration of Response (DoR): DoR is defined from the time of first CMR or PMR (according to Lugano criteria) to the date of first documented disease progression, relapse or death from any cause. If a subject has not progressed or died, DoR will be censored at the date of tumor assessment. • Quality of Life (QoL): QoL scale measurements will be the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), and the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym LymS) subscale. Secondary safety endpoints Summary of study drug administration including treatment duration, total dose and percentage of planned dose will be displayed. Permanent treatment discontinuation and reasons will be summarized. Adverse events and concomitant medications will be described. AE will be classified using the latest version of Medical Dictionary for Drug Regulatory Activities (MedDRA) coding system at the time of database lock. The severity of the toxicities will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) whenever possible. AE will be described by system organ class and prefer | — |
Countries
France
Contacts
Public ContactStéphanie DOYEN
LYSARC
Outcome results
None listed