STUDY EVALUATING EFFECTIVNESS of ANTICD20XCD3 BISPECIFIC ANTIBODIES FOR RELAPSE/REFRACTORY LYMPHOMAS AFTER CART THERAPY

Phase 1

• Conditions: 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: 21.0Level: PTClassification code 10012822Term: Diffuse large B-cell lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10012821Term: Diffuse large B-cell lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10026801Term: Mantle cell lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10026800Term: Mantle cell lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10036714Term: Primary mediastinal large B-cell lymphoma refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10036713Term: Primary mediastinal large B-cell lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 23.0Level: PTClassification code 10065856Term: Non-Hodgkin's lymphoma unspecified histology indolentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 23.0Level: PTClassification code 10061871Term: Non-Hodgkin's lymphoma transformed recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2020-001985-12-FR
• Lead Sponsor: YSARC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-12-08
• Last Update Posted: 26 February 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 78

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

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified