Large B-cell Lymphoma
Conditions
Brief summary
The aim of this study is to evaluate the efficacy and safety of CAR T-cell therapy in combination with glofitamab for the treatment of relapsed/refractory large B-cell lymphoma with high-risk prognostic factors.
Interventions
BIOLOGICALCAR T-cell therapy
Participants will receive CAR T-cell therapy via infusion on Day 0 (given as per treatment guidelines). Prior to CAR T-cell Therapy, participants will begin receiving lymphodepleting chemotherapy on Days -5 through -3 (given as per treatment guidelines).
DRUGGlofitamab
Glofitamab is given intravenously at a dose of 2.5mg over 4 hours on Cycle 1 Day 8. Glofitamab is given intravenously at a dose of 10mg over 2 hours on Cycle 1 Day 15. Glofitamab is given intravenously at a dose of 30mg over 2 hours on Day 1 of Cycles 2-6 (as relevant).
DRUGObinutuzumab
Obinutuzumab pre-treatment is given intravenously at a dose of 1g on Cycle 1 Day 1.
Sponsors
Ruijin Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Signed Informed Consent Form * Histologically confirmed large B-cell lymphoma with CD19 and CD20 expression, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS); primary mediastinal large B-cell lymphoma (PMBCL); high-grade B-cell lymphoma (HGBL); and transformed follicular lymphoma * Patients who have relapsed or are refractory to at least prior first-line therapy, including anthracycline-containing chemotherapy regimens and anti-CD20 monoclonal antibody therapy * Patients must be willing to receive CAR-T and Glofitamab therapy and be deemed suitable for CAR-T and Glofitamab treatment by the investigator * Presence of at least one high-risk prognostic factor: (1) extranodal involvement; (2) maximum tumor diameter \> 4 cm; (3) TP53 mutation * ECOG Performance Status of 0, 1, or 2 * Life expectancy ≥12 weeks * Adequate hematologic function (unless due to underlying disease, such as extensive bone marrow involvement, or secondary to lymphoma-related splenomegaly as determined by the investigator, but transfusion of blood products is allowed) and adequate liver, renal, pulmonary, and cardiac function Key
Exclusion criteria
* Hypersensitivity to any study drug or excipient * History of allogeneic stem cell transplantation * Patients with active viral hepatitis requiring treatment as determined by the investigator: chronic hepatitis B virus carriers with HBV DNA ≥ 500 IU/mL (2500 copies/mL) (HBV DNA testing only for patients who test positive for hepatitis B surface antigen or core antibody); patients who test positive for HCV RNA (HCV testing only for patients who test positive for HCV antibody) * Presence of uncontrolled infection, cardio-cerebrovascular disease, coagulopathy, or autoimmune disease, etc * History of HIV infection * Presence or concurrence of other malignancies within the past 2 years, with the exception of cured cervical carcinoma in situ, non-melanoma skin cancer and superficial bladder tumors * Previous anti-CD19 CAR-T therapy is not allowed * Pregnant or lactating women * Other uncontrollable medical condition that may interfere the participation of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) Rate | Up to 2 years | CR rate is defined as the percentage of participants achieving CR per the Lugano Classification as determined by study investigators |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 2 years | ORR is defined as the percentage of participants achieving either CR or partial response (PR) per the Lugano Classification as determined by study investigators |
| Duration of Response (DoR) | Up to 2 years | DoR is defined only for participants who experience an objective response and is the time from the first objective response to disease progression or death from any cause. |
| Progression-Free Survival (PFS) | Up to 2 years | PFS is defined as the time from leukapheresis to first documented progression or death from any cause. |
| Overall Survival (OS) | Up to 2 years | OS is defined as the time from leukapheresis to death from any cause. |
| Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) | Up to 2 years | Assessed by CTCAE criteria v5 and ASTCT 2019 criteria for CRS/ICANS adverse events. |
Countries
China
Contacts
Primary ContactWeili Zhao
Outcome results
None listed