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

Official title

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.

Overview

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 .

Interventions

• Other 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
• 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

Primary outcome measures

• Complete remission rate(CRR) [Time frame: At the end of 3 months after CAR-T infusion]

Secondary outcome measures (4)

• Major adverse reactions [Time frame: From enrollment to 1 month after CAR-T infusion of last patient]
• Time to bone marrow hematopoietic reconstitution [Time frame: From enrollment to 3 months after stem cell infusion of last patient]
• 2-year progression-free survival(PFS) [Time frame: From enrollment to 2-year after the end of last patient's treatment]
• 2-year overall survival(OS) [Time frame: From enrollment to 2-year after the end of last patient's treatment]

Eligibility criteria

Inclusion criteria

• Age ≥18 years.
• Histologically confirmed aggressive B-NHL.
• Life expectancy >3 months.
• 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

• 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.

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

• severe hepatic and renal function abnormalities (alanine aminotransferase, bilirubin, creatinine > 2 times the upper limit of normal);
• Presence of organic heart disease with resulting clinical symptoms or abnormal cardiac function (NYHA cardiac function classification ≥ grade 2);
• ECG QTc interval >500 ms;
• active hepatitis B/hepatitis C;
• uncontrolled active infection;
• human immunodeficiency virus infection;
• concurrent other tumors requiring treatment or intervention;
• current or anticipated need for systemic corticosteroid therapy;
• pregnant or lactating women;
• abandonment of consolidation autologous hematopoietic stem cell transplantation for financial reasons;
• other psychological conditions that prevent the patient from participating in the study or signing the informed consent form;
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• the First Affiliated Hospital of Soochow University — Suzhou

Identifiers

NCT: NCT07059741 · 2024415

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗