NCT06552572

Glofitamab in Relapsed or Refractory Diffuse Large B-cell Lymphoma After CD19 Chimeric Antigen Receptor T-cell Therapy

Phase II Study of Glofitamab Therapy in Relapsed or Refractory Diffuse Large B-cell Lymphoma Patients Achieving Response After CD19 Chimeric Antigen Receptor T-cell Therapy

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Samsung Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The objective of this clinical trial is to determine whether the CD20-CD3 bispecific antibody, glofitamab, is effective in treating residual diffuse large B-cell lymphoma (DLBCL) in adults who have responded to CD19 Chimeric antigen receptor (CAR) T-cell therapy for their relapsed or refractory DLBCL. Additionally, the trial will assess the safety of glofitamab in patients undergoing CD19 CAR T-cell therapy. The primary questions to be addressed are: Does glofitamab reduce the number of participants experiencing disease progression following CD19 CAR T-cell therapy? What are the medical complications in participants already treated with CD19 CAR T-cell therapy when administered glofitamab? Participants are required to: Receive glofitamab every 21 days for 12 cycles or until disease progression. Attend the clinic for checkups and tests every three weeks.

Detailed description

1. Background CD19 CAR T-cell therapy has proven to be a highly effective adoptive cell therapy, evidenced by the significant complete response rates in patients with B-cell acute lymphoblastic leukemia (B-ALL) and large B-cell lymphoma (DLBCL), leading to FDA approvals. While CAR-T cell therapy has been a lifeline for patients unresponsive to other treatments, 60% still experience disease progression despite 40% achieving a complete response. The durability of remission may be compromised by factors such as loss of the target antigen CD19, inhibitory receptor expression, absence of costimulatory ligands, limited CAR-T cell expansion or persistence, and impaired effector function due to exhaustion. Glofitamab, a novel bispecific T-cell engaging antibody, binds bivalently to CD20 on B-cells and monovalently to CD3 on T-cells. Pharmacodynamic studies show that glofitamab administration leads to T-cell activation, indicated by increased granzyme B expression, suggesting it may alter the tumor immune environment towards T-cell activation. We hypothesize that glofitamab could bridge the gap between CAR T- or cytotoxic cells and tumor cells, mitigating immune exhaustion. This could potentially enhance survival by preventing immune cell exhaustion and boosting the efficacy of immunotherapy. Therefore, we aim to conduct a prospective study to augment the therapeutic efficacy of CAR-T cells by bolstering effector cells within the tumor immune environment, using glofitamab as a subsequent treatment post-CAR-T cell therapy. 2. Study population * Patients who show partial response at 1 or 3 months after CD19 CAR T-cell therapy for thier relapsed or refractory DLBCL (RR-DLBCL) 3. Treatment protocol A) Glofitamab every 21 days for 12 cycles or until progression. 1. First cycle * Obinutuzumab (GPT) 1000mg (D1) * Glofitamab step up dosing 2.5mg (D8) → 10mg (D15) 2. After the first cycle (completed priming) * Glofitamab 30mg IV every 3 weeks B) Supportive care * Concomitant administration is recommended during the period of glofitamab administration. Changes in dose and duration are at the decision of the investigators. * TMP-SMX 400/800mg QD * Acyclovir 200-400mg QD 4. Sample sixe - Previous phase II clinical trials of Tixacel associated a treatment response rate of 40-52% in RR-DLBCL, a 1-year progression-free survival (PFS) of 33%-44%, and a 2-year PFS of 31-36% \[5, 6 \]. The new maintenance treatment group used a better effect than the previous physiotherapy treatment and Tixacel treatment alone, setting everyone up. Therefore, the measurement range: H0 S0=S1 vs H1: S0≠S1; S0, S1: According to the definition as the 1-year PFS of the Historical Control group (S0) and the test group (S1), the 1-year PFS of the Historical Control group was 37%, power 90%, law level 5%, training period 2 years, follow-up Assuming that the period of 1 year and the survival time group are exponential, under the hypothesis, the 1-year PFS of the test group is set to 60%, the number of subjects is 28, and the expected event occurrence is 18. With a dropout rate of 5%, the final number of registered participants is 30.

Conditions

• Diffuse Large B Cell Lymphoma

Interventions

Type	Name	Description
DRUG	Glofitamab	Glofitamab is administered to patients who have residual disease after CD19 CAR T-cell therapy for their relapsed or refractory diffuse large B-cell lymphoma

Timeline

• Start date: 2024-11-26
• Primary completion: 2026-06-30
• Completion: 2028-12-30
• First posted: 2024-08-14
• Last updated: 2025-05-21

Locations

1 site across 1 country: South Korea

Regulatory

• FDA-regulated drug study