Glofitamab Bridging ASCT for Patients With Relapsed or Refractory DLBCL

NCT ID: NCT06682130

Last Updated: 2025-07-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-10
• Study Completion Date: 2029-11-10

Brief Summary

The objective of this study is to evaluate the efficacy and safety of the Glofitamab bridging ASCT regimen in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and to provide better clinical benefits to these patients.

Detailed Description

This study seeks to include patients aged 18 to 70 years with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) who have undergone at least a second-line systemic treatment, excluding those with prior resistance to Glofitamab. Based on their disease status following the second-line treatment, participants will be categorized into three groups: A, B, and C. Group A will consist of patients who exhibit partial response (PR) or are circulating tumor DNA (ctDNA) positive after second-line treatment and are planning to undergo autologous stem cell transplantation (ASCT) or Glofitamab as a bridging therapy to ASCT. Group B will include patients who achieve complete response (CR) and are ctDNA negative post-second-line treatment, and they will receive ASCT as consolidation therapy. Patients in Group B who achieved CR and were ctDNA negative following second-line treatment will proceed directly to ASCT consolidation therapy. In Group C, patients who exhibited stable disease (SD) or progressive disease (PD) after second-line treatment were reassessed following two cycles of Glofitamab. Those who attained PR subsequently underwent ASCT consolidation therapy, whereas patients achieving CR had the option to either undergo ASCT or continue with Glofitamab maintenance therapy. Patients with SD or PD were excluded from the study. Patients exhibiting SD or PD were excluded from the cohort. Individuals who have successfully undergone autologous transplantation and subsequent maintenance therapy with Glofitamab will be monitored for assessments of efficacy and survival outcomes.

Conditions

Diffuse Large B-cell Lymphoma(DLBCL)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Glofitamab bridging ASCT Regimen

After at least second-line treatment, patients will be divided into three groups based on their disease status: Group A includes patients with partial response (PR) or ctDNA positivity who plan to receive ASCT or Glofitamab (specification: 10 mg per tube; dosage: 2.5 mg on day 8) as a bridge to ASCT; Group B includes patients with complete response (CR) and ctDNA negativity who will proceed directly to ASCT; Group C includes patients with stable or progressive disease (SD/PD) who will be assessed after two cycles of Glofitamab (Specification: 10mg per tube;Dosage: cycle 1: 2.5mg d8；10mg d15；cycle 2: 30mg d21). Those achieving PR will undergo ASCT, those with CR can choose ASCT or continue Glofitamab, and those with SD/PD will be removed from the group.

Group Type: EXPERIMENTAL

Group A：Patients with PR or ctDNA positivity after salvage treatment

Intervention Type: DRUG

1. Immunotargeted therapy

• Ottuzumab introvenous infusion, 1000mg day1;
• Glofitamab introvenous infusion Group A: 2.5mg day8

2. Autologous stem cell transplantation SEAM regimen

• Simustine 250mg/m2 orally, day1
• Etoposide 200mg/m2 intravenous infusion, day2-5
• Cytarabine 400mg/m2 intravenous infusion, day2-5
• Metformin 140mg/m2 intravenous infusion, day6; Patients in Group A who intend to receive Glofitamab+ASCT will receive Glofitamab 2.5mg on day8 and start ASCT pretreatment on day15.

Group B: Patients with CR and ctDNA negative after salvage treatment

Intervention Type: PROCEDURE

Group B patients initiated ASCT treatment directly after evaluating the efficacy of salvage treatment

Group C: Patients with SD/PD after posterior treatment

Intervention Type: DRUG

1. Immunotargeted therapy

• Ottuzumab introvenous infusion, 1000mg day1;
• Glofitamab introvenous infusion Group C: cycle1 2.5mg day8, 10mg day15 cycle2 30mg day21

2. Autologous stem cell transplantation SEAM regimen

• Simustine 250mg/m2 orally, day1
• Etoposide 200mg/m2 intravenous infusion, day2-5
• Cytarabine 400mg/m2 intravenous infusion, day2-5
• Metformin 140mg/m2 intravenous infusion, day6;

After two treatment cycles with Glofitamab, patients in group C had a PET-CT to assess efficacy. Those with partial remission proceeded to ASCT consolidation, those with complete remission chose between ASCT or Glofitamab maintenance, and those with stable disease or progressive disease exited the trial.

Interventions

Group A：Patients with PR or ctDNA positivity after salvage treatment

1. Immunotargeted therapy

• Ottuzumab introvenous infusion, 1000mg day1;
• Glofitamab introvenous infusion Group A: 2.5mg day8

2. Autologous stem cell transplantation SEAM regimen

• Simustine 250mg/m2 orally, day1
• Etoposide 200mg/m2 intravenous infusion, day2-5
• Cytarabine 400mg/m2 intravenous infusion, day2-5
• Metformin 140mg/m2 intravenous infusion, day6; Patients in Group A who intend to receive Glofitamab+ASCT will receive Glofitamab 2.5mg on day8 and start ASCT pretreatment on day15.

Intervention Type: DRUG

Group B: Patients with CR and ctDNA negative after salvage treatment

Group B patients initiated ASCT treatment directly after evaluating the efficacy of salvage treatment

Intervention Type: PROCEDURE

Group C: Patients with SD/PD after posterior treatment

1. Immunotargeted therapy

• Ottuzumab introvenous infusion, 1000mg day1;
• Glofitamab introvenous infusion Group C: cycle1 2.5mg day8, 10mg day15 cycle2 30mg day21

2. Autologous stem cell transplantation SEAM regimen

• Simustine 250mg/m2 orally, day1
• Etoposide 200mg/m2 intravenous infusion, day2-5
• Cytarabine 400mg/m2 intravenous infusion, day2-5
• Metformin 140mg/m2 intravenous infusion, day6;

After two treatment cycles with Glofitamab, patients in group C had a PET-CT to assess efficacy. Those with partial remission proceeded to ASCT consolidation, those with complete remission chose between ASCT or Glofitamab maintenance, and those with stable disease or progressive disease exited the trial.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients with diffuse large B-cell lymphoma (DLBCL) confirmed by histopathology/cytology using the 2022 World Health Organization (WHO) Classification of Diseases;

2. Patients with R/R DLBCL who have received at least two lines of systemic treatment;

3. Age range: 18-70 years old, male or female not limited;

4. When the disease recurs or is difficult to treat, there are assessable lesions (lymph node diameter ≥ 1.0cm; or skin lesions assessable by physical examination);

5. Expected lifespan>3 months;

6. No previous transplantation treatment has been performed;

7. ECOG score 0-1 points;

8. Appropriate organ function:

Cardiac function: ejection fraction ≥ 50%, asymptomatic arrhythmia; Liver function: alanine aminotransferase and aspartate aminotransferase ≤ 2 times the upper limit of normal, total bilirubin<2 times the upper limit of normal; Renal function: serum creatinine clearance rate ≥ 80 mL/min, creatinine<160 umol/l; Pulmonary function: Without oxygen inhalation, SPO2>90%, FEV1, FVC, and DLCO ≥ 50% predicted values;

9. Adequate bone marrow reserve is defined as:

Hemoglobin ≥ 9g/dL, Platelet count ≥ 70 × 10 ^ 9/L, The absolute value of neutrophils is ≥ 1.0 × 10 ^ 9/L, If accompanied by bone marrow invasion, platelet count ≥ 50 × 10 ^ 9/L, absolute neutrophil count ≥ 0.75 × 10 ^ 9/L, The number of CD34+cells is ≥ 2.0 × 109/kg.

10. The patient has the ability to understand and is willing to provide written informed consent.

11. Subjects with fertility or potential for fertility must be willing to undergo contraception from the date of registration in this study until the study follow-up period.

Exclusion Criteria

-1) Previously underwent autologous hematopoietic stem cell transplantation; 2) HIV infection and/or active hepatitis B or C; 3) Uncontrolled active infections; 4) Severe liver and kidney dysfunction (alanine aminotransferase, bilirubin, creatinine>3 times the upper limit of normal); 5) Existence of organic heart disease or severe arrhythmia, leading to clinical symptoms or abnormal heart function (NYHA functional class ≥ 2); 6) Simultaneously present other tumors that require treatment or intervention; 7) Previous or current history of vascular embolism; 8) Pregnant or lactating women; 9) In a state of severe immune suppression; 10) Other psychological conditions that hinder patients from participating in research or signing informed consent forms.

11) According to the researcher's assessment, it is unlikely that the subjects will complete all the required study visits or procedures, including follow-up visits, or meet the requirements for participation in the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital of Soochow University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhengming Jin

Role: CONTACT

jinzhengming519519@163.com

67781856

Changju Qu

Role: CONTACT

qcj310@163.com

67781856

Facility Contacts

Zhengming Jin

Role: primary

jinzhengming519519@163.com

67781856

Changju Qu

Role: backup

qcj310@163.com

67781856

Other Identifiers

2024378

Identifier Type: -

Identifier Source: org_study_id