Clinical trial NCT06682130: Glofitamab Bridging ASCT for Patients With Relapsed or Refractory DLBCL
Official title: A Prospective Study of Glofitamab Bridging Autologous Peripheral Blood Stem Cell Transplantation for Patients With Relapsed and Refractory Diffuse Large B Cell Lymphoma.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diffuse Large B-cell Lymphoma(DLBCL)
Keywords: Glofitamab
autologous stem cell transplantation
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2024-11-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Overall response rate(ORR)
timeFrame: Up to 1-month after treatment with Glofitamab bridging ASCT Regimen
measure: Complete remission rate(CRR)
timeFrame: Up to 1-month after treatment with Glofitamab bridging ASCT Regimen
Secondary outcomes:
measure: Main adverse reactions
timeFrame: Start from the first day of Immunotargeted therapy to 1 month after treatment with Glofitamab bridging ASCT Regimen
measure: Overal survival(OS)
timeFrame: Up to 24 months after the end of last patients' treatment
measure: Progression-free survival(PFS)
timeFrame: Up to 24 months after the end of last patients' treatment
measure: Overall response rate(ORR)
timeFrame: up to 3-week after treatment with Immunotargeted therapy
measure: Complete remission rate(CRR)
timeFrame: up to 3-week after treatment with Immunotargeted therapy
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
Study officials:
References: