Radiation‑optimized autologous stem cell transplant followed by sequential CAR‑T for relapsed/refractory aggressive B‑cell NHL

A Prospective Study of Integrated Radiotherapy-optimized ASCT Sequential CAR-T Therapy on the Efficacy and Safety of Patients With Relapsed and Refractory Aggressive B-cell Non-Hodgkin Lymphoma.

This trial will try combining targeted radiotherapy, a reduced‑intensity SEAM/TB conditioning with autologous stem cell transplant, and sequential CAR‑T cell therapy in adults with relapsed or refractory aggressive B‑cell NHL to see if it improves disease control and survival.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The First Affiliated Hospital of Soochow University (Academic / other)
• Drugs / interventions: CAR-T, chimeric antigen receptor, chemotherapy
• Locations: 1 site (Suzhou, Jiangsu)
• Trial ID: NCT07059741 on ClinicalTrials.gov

What this trial studies

This interventional protocol enrolls adults with relapsed/refractory aggressive B‑cell non‑Hodgkin lymphoma who have had at least two prior systemic therapies. Participants are stratified by post‑salvage status into two cohorts based on PET/CT and circulating tumor DNA: one cohort receives low‑dose radiotherapy plus reduced‑intensity SEAM/TB conditioning before ASCT and CAR‑T, and the other receives high‑dose radiotherapy with the same reduced conditioning before ASCT and CAR‑T. All subjects proceed to autologous stem cell transplantation followed by sequential CAR‑T infusion and are followed longitudinally for safety, response, and survival outcomes. The design tests whether tailoring radiation dose by imaging and ctDNA can improve tolerability and longer‑term control when combined with ASCT and CAR‑T.

Who should consider this trial

Good fit: Adults aged 18 or older with histologically confirmed relapsed or refractory aggressive B‑cell NHL who have received at least two prior systemic therapies and have adequate organ function and marrow reserve are the intended participants.

Not a fit: Patients with severe hepatic or renal dysfunction, inadequate marrow reserve, life expectancy under three months, or who cannot tolerate/attend ASCT and CAR‑T at the study center are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this combined approach could increase durable remissions and overall survival for patients with relapsed/refractory aggressive B‑cell NHL while personalizing radiation intensity.

How similar studies have performed: CAR‑T therapy and ASCT each have established roles in relapsed/refractory B‑cell NHL, but the specific integration of radiotherapy‑optimized ASCT followed by sequential CAR‑T is a novel multimodal strategy with limited prior clinical data.

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.

Where this trial is running

Suzhou, Jiangsu

• the First Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Changju Qu

Conditions Aggressive B-Cell Non-Hodgkin' s Lymphoma; Radiotherapy; autologous stem cell transplantation; Relapsed and refractory; circulating tumor DNA; Chimeric antigen receptor T-cell therapy