Treatment by a Bispecific CD3xCD20 Antibody for Relapse/Refractory Lymphomas After CAR T-cells Therapy

NCT04703686 | Completed Phase 2

• 1 other identifier: BiCAR
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 19

Brief Summary

This study is a multicenter phase II trial including 2 cohorts of patients in Refractory/Relapse disease at least 1 month after CAR T-cells therapy:

• cohort 1: DLBCL patients
• cohort 2: PMBL, mantle cell lymphoma, transformed indolent NHL (t-iNHL) or iNHL CAR T-cells Refractory/Relapse status will be determined by PET-CT central review allowing inclusion in this trial. Patients enrolled will then receive a pre-phase of obinutuzumab followed by experimental treatment:11 cycle of glofitamab. 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 DLBCL (cohort 1) disease after anti-CD19 CAR T-cells therapy

Conditions

Refractory Indolent Adult Non-Hodgkin Lymphoma; Refractory Primary Mediastinal Large B-Cell Cell Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Transformed B-cell Non-Hodgkin Lymphoma; Diffuse Large B-Cell Lymphoma Refractory

Keywords

Post Car T-cells therapy

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  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

  4 years

Secondary Outcomes (31)

• Metabolic response rates according to Lugano classification

  At the end of Cycle 2 (1st cycle of 14 days and subsequent cycles of 21 days)

• Metabolic response rates according to Lugano classification

  At the end of Cycle 6 (1st cycle of 14 days and subsequent cycles of 21 days)

• Metabolic response rates according to Lugano classification

  At the end of Cycle 9 (1st cycle of 14 days and subsequent cycles of 21 days)

• Metabolic response rates according to Lugano classification

  At the end of Cycle 11 (1st cycle of 14 days and subsequent cycles of 21 days)

• Progression Free Survival (PFS)

  At the end of Cycle 2 (1st cycle of 14 days and subsequent cycles of 21 days)

Study Arms (1)

Obinutuzumab + RO7082859

EXPERIMENTAL

Drug: Obinutuzumab; Drug: RO7082859

Interventions

Obinutuzumab DRUG

1000mg - prephase - one infusion at D-3

Also known as: gazyva

Obinutuzumab + RO7082859

RO7082859 DRUG

2.5 mg D1C1, 10 mg D3C1, then 30 mg D8C1 and D1 every 21 days (C2-C11, D1C2 starts 14 days after D1C1)

Also known as: glofitamab

Obinutuzumab + RO7082859

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)
• First metabolic progression, first relapse or no metabolic response after CAR T-cells infusion must be confirmed by PET-CT central review for enrollment
• DLBCL with demonstrated lymphoma cells-expressing CD20 at relapse post CAR T-cells as demonstrated by biopsy before enrollment (cohort 1 only)
• Aged 18 years or more with no upper age limit
• ECOG performance status 0 or 1
• 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
• No persistant CAR-T neurotoxicity symptoms or previous experience during CAR T-cells therapy of neurotoxicity grade \> 3
• Adverse events from prior anti-cancer therapy must have resolved to Grade ≤ 1 (hematological toxicities excepted)
• 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)
• 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
• Adequate renal function: creatinine clearance (CrCl) calculated by MDRD/cockcroft -Gault formula of ≥ 30 mL/min
• Negative serum or urinary pregnancy test within 7 days prior to study treatment in women of childbearing potential
• 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
• 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

You may not qualify if:

• 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
• Patients with CLL, Richter and Burkitt lymphoma
• Patients relapsing or progressing within 1 months (30 days) after CAR T-cells therapy
• 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
• Current or past history of detectable cerebrospinal fluid lymphoma cells, or with a history of CNS lymphoma localization or primary CNS lymphoma
• Current or past history of cerebral disorders
• Any serious psychiatric illness that would prevent the subject from signing the informed consent form.
• Patients with history of macrophage activation syndrome (MAS) / hemophagocytic lymphohistiocytosis (HLH)
• 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
• 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)
• Any serious active disease or co-morbid medical condition
• Clinically significant history of liver disease or cirrhosis
• 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

Sponsors & Collaborators

• The Lymphoma Academic Research Organisation: lead

Study Sites (19)

CHU Amiens Picardie Site sud

Amiens, France

Location

CHU de Clermont Ferrand

Clermont-Ferrand, 63000, France

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

CHU de Dijon - Hôpital le Bocage

Dijon, 21034, France

Location

CHU de Grenoble

Grenoble, 38043, France

Location

CHRU Lille - Hôpital Claude Huriez

Lille, 59037, France

Location

CHU Montpellier

Montpellier, 34295, France

Location

CHU Nantes

Nantes, 44093, France

Location

Hôpital Saint Louis

Paris, 75475, France

Location

Hopital Necker enfants malades

Paris, 7574, France

Location

APHP - Hôpital de la Pitiè Salpetrière

Paris, France

Location

APHP - Hôpital Saint Antoine

Paris, France

Location

CHU de Bordeaux - Hôpital Haut Leveque

Pessac, 33604, France

Location

CHU Lyon Sud

Pierre-Bénite, 69130, France

Location

CHU de Rennes - Hôpital Pontchaillou

Rennes, 35033, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

IUCT Oncopole

Toulouse, 31059, France

Location

CHU Tours Hopital Bretonneau

Tours, 37044, France

Location

CHU de Brabois

Vandœuvre-lès-Nancy, France

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

obinutuzumab; glofitamab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Guillaume Cartron, MD,PhD

  Lymphoma Study Association

  STUDY CHAIR

• Pierre Sesques, MD

  Lymphoma Study Association

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2021
• First Posted: January 11, 2021
• Study Start: March 30, 2021
• Primary Completion: January 10, 2023
• Study Completion: May 21, 2025
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (19)