Integrated Radiotherapy-optimized ASCT Sequential CAR-T Therapy for Patients With Relapsed and Refractory B-NHL

NCT ID: NCT07059741

Last Updated: 2025-07-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-10
• Study Completion Date: 2028-12-10

Brief Summary

This study aims to investigate a novel therapeutic strategy of integrated radiotherapy before autologous stem cell transplantation (ASCT) sequential chimeric antigen receptor T-cell(CAR-T) therapy for patients with relapsed/refractory(R/R) aggressive B-cell non-Hodgkin lymphoma (B-NHL). By evaluating the efficacy and safety of this multimodal approach, we seek to provide a theoretical foundation and clinical data to optimize outcomes for relapsed/refractory aggressive B-NHL patients.

Detailed Description

This trial will enroll R/R aggressive B-NHL patients aged ≥18 years who have undergone at least two prior lines of systemic therapy. Participants will be stratified into two cohorts based on post-salvage therapy disease status:

Cohort 1 (PET/CT-, ctDNA+): Patients will receive low-dose radiotherapy (RT) combined with reduced-intensity SEAM/TB chemotherapy as a conditioning regimen, followed by ASCT and sequential CAR-T therapy.

Cohort 2 (PET/CT+, ctDNA+): Patients will receive high-dose RT combined with reduced-intensity SEAM/TB chemotherapy as a conditioning regimen, followed by ASCT and sequential CAR-T therapy.

All patients completing the combined ASCT-CAR-T protocol will undergo longitudinal follow-up for safety, efficacy survival outcomes .

Conditions

Aggressive B-Cell Non-Hodgkin's Lymphoma (NHL)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Cohort 1 (PET/CT-, ctDNA+)

Patients will receive low-dose radiotherapy (RT) combined with reduced-intensity SEAM/TB chemotherapy as a conditioning regimen, followed by autologous stem cell transplantation (ASCT) and sequential CAR-T cell therapy.

Group Type: EXPERIMENTAL

integrated low-dose RT with reduced SEAM/TB conditioning before ASCT sequential CAR-T

Intervention Type: OTHER

1. RT regimen:

localized low dose RT: 1-1.5Gy/fraction*5fractions

2. Reduced dose SEAM regimen (CNS uninvolved):

• Simustine 250mg/m2 d-6 orally
• Cytarabine 200mg/m2 q12h d-5~d-4 intravenous infusion
• Etoposide 100mg/m2 q12h d-5~d-4 intravenous infusion
• Melphalan 140mg/m2 q12h d-3 intravenous infusion

3. TB regimen (CNS involvement):

• Thiotepa 250mg/m2 qd, d-8~d-6 intravenous infusion
• Busulfan 0.8mg/kg q6h d-5~d-3 intravenous infusion

Cohort 2 (PET/CT+, ctDNA+)

Patients will receive high-dose RT combined with reduced-intensity SEAM/TB chemotherapy as a conditioning regimen, followed by ASCT and sequential CAR-T cell therapy.

Group Type: EXPERIMENTAL

integrated high-dose RT with reduced SEAM/TB conditioning before ASCT sequential CAR-T

Intervention Type: OTHER

1. RT regimen:

localized high dose RT: 3-6Gy/fraction*5fractions

2. Reduced dose SEAM regimen (CNS uninvolved):

• Simustine 250mg/m2 d-6 orally
• Cytarabine 200mg/m2 q12h d-5~d-4 intravenous infusion
• Etoposide 100mg/m2 q12h d-5~d-4 intravenous infusion
• Melphalan 140mg/m2 q12h d-3 intravenous infusion

3. TB regimen (CNS involvement):

• Thiotepa 250mg/m2 qd, d-8~d-6 intravenous infusion
• Busulfan 0.8mg/kg q6h d-5~d-3 intravenous infusion

Interventions

integrated low-dose RT with reduced SEAM/TB conditioning before ASCT sequential CAR-T

1. RT regimen:

localized low dose RT: 1-1.5Gy/fraction*5fractions

2. Reduced dose SEAM regimen (CNS uninvolved):

• Simustine 250mg/m2 d-6 orally
• Cytarabine 200mg/m2 q12h d-5~d-4 intravenous infusion
• Etoposide 100mg/m2 q12h d-5~d-4 intravenous infusion
• Melphalan 140mg/m2 q12h d-3 intravenous infusion

3. TB regimen (CNS involvement):

• Thiotepa 250mg/m2 qd, d-8~d-6 intravenous infusion
• Busulfan 0.8mg/kg q6h d-5~d-3 intravenous infusion

Intervention Type: OTHER

integrated high-dose RT with reduced SEAM/TB conditioning before ASCT sequential CAR-T

1. RT regimen:

localized high dose RT: 3-6Gy/fraction*5fractions

2. Reduced dose SEAM regimen (CNS uninvolved):

• Simustine 250mg/m2 d-6 orally
• Cytarabine 200mg/m2 q12h d-5~d-4 intravenous infusion
• Etoposide 100mg/m2 q12h d-5~d-4 intravenous infusion
• Melphalan 140mg/m2 q12h d-3 intravenous infusion

3. TB regimen (CNS involvement):

• Thiotepa 250mg/m2 qd, d-8~d-6 intravenous infusion
• Busulfan 0.8mg/kg q6h d-5~d-3 intravenous infusion

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Age ≥18 years.

2. Histologically confirmed aggressive B-NHL.

3. Life expectancy >3 months.

4. Appropriate organ function:

Cardiac function: cardiac ejection fraction ≥50%; Liver function: alanine aminotransferase and glutamic aminotransferase ≤ 2 times the upper limit of normal values; renal function: serum creatinine clearance ≥80 mL/min; serum creatinine <160 mmol/L Lung function: SPO2>91% without oxygen intake

5. Adequate bone marrow reserve defined as:

hemoglobin ≥90 g/L. platelet count ≥70 x 10^9/L. absolute neutrophil count ≥1.5 x 10^9/L.

6. The patient is capable of understanding and willing to provide written informed consent.

7. Subjects of childbearing or childbearing potential must be willing to practice birth control from the date of enrollment in this study until study follow-up.

Exclusion Criteria

1. severe hepatic and renal function abnormalities (alanine aminotransferase, bilirubin, creatinine > 2 times the upper limit of normal);

2. Presence of organic heart disease with resulting clinical symptoms or abnormal cardiac function (NYHA cardiac function classification ≥ grade 2);

3. ECG QTc interval >500 ms;

4. active hepatitis B/hepatitis C;

5. uncontrolled active infection;

6. human immunodeficiency virus infection;

7. concurrent other tumors requiring treatment or intervention;

8. current or anticipated need for systemic corticosteroid therapy;

9. pregnant or lactating women;

10. abandonment of consolidation autologous hematopoietic stem cell transplantation for financial reasons;

11. other psychological conditions that prevent the patient from participating in the study or signing the informed consent form;

12. Subjects who, in the judgment of the investigator, are unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or do not meet the requirements for participation in the study.

• Minimum Eligible Age: 18 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

Changju Qu

Role: CONTACT

qcj310@163.com

67781856

Facility Contacts

Changju Qu

Role: primary

qcj310@163.com

67781856

Other Identifiers

2024415

Identifier Type: -

Identifier Source: org_study_id