CAR-T Following ASCT for Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (R/R B-NHL) With High-Risk Prognostic Factors

Shanghai Jiao Tong University

Status and phase: Enrolling; Phase 2

Conditions: B-cell Non Hodgkin Lymphoma

Treatments: Drug: Relmacabtagene autoleucel (relma-cel); Other: autologous stem-cell transplantation

Study type: Interventional

Funder types: Other

Identifiers

NCT06365671

ASCT-CART

Details and patient eligibility

About

Clinical trial for the safety and efficacy of CD19 CAR-T following autologous hematopoietic stem cell transplantation (ASCT) for Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (R/R B-NHL) with High-Risk Prognostic Factors

Full description

This is a single-center, single-arm, open-label, prospective clinical trial to evaluate the efficacy and safety of CD19 CAR-T infusion following high-dose chemotherapy and autologous stem-cell transplantation (HDT/ASCT) in relapsed or refractory B-cell Non-Hodgkin's Lymphoma patients with high-risk prognostic factors (extranodal involvement/bulky mass ≥5 cm in diameter/TP53 alterations). CD19 CAR-T will be infused on day +3 (±1d) with a fixed dose of 100X10^6. The study will assess the safety and efficacy of this combinational therapy, including the investigators assessed the best complete response rate (BCR) in 3 months (primary endpoint), objective response rates, survivals, incidence and severity of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hematological, and other non-hematological toxicities of the subjects.

Enrollment: 16 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Histologically confirmed B-cell non-Hodgkin's lymphoma including the following types

   • diffuse large B-cell lymphoma
   • high-grade B-cell lymphoma with or without MYC and BLC2 and/or BCL6 rearrangement
   • transformed lymphoma
   • primary mediastinal large B-cell lymphoma
   • follicular lymphoma (FL)

2. Relapsed or refractory diseases fulfilling one of the following criteria (individuals must have received anti-CD20 monoclonal antibody and anthracycline-containing chemotherapy regimen)

   • Primary refractory disease, defined as disease progression after first-line immunochemotherapy or disease progression within 6 weeks of the end of the last chemotherapy
   • Stable disease (SD) as best response after at least 4 cycles of first-line therapy
   • Partial response (PR) as best response after at least 6 cycles of first-line therapy (biopsy-proven residual disease is needed for individuals with Deauville score of 4)
   • PR as best response after at least 2 cycles of second-line therapy
   • Disease relapse ≤12 months after the completion of first-line immunochemotherapy
   • Relapsed or refractory disease after ≥2 lines of chemotherapy

3. Presence of at least one of the following high-risk prognostic factors: (1) extranodal involvement; (2) maximum diameter of the bulky mass ≥5 cm; (3) TP53 gene alterations

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

5. Eligible for HDCT/ASCT based on the investigator's assessment and are scheduled to undergo an ASCT sequential CAR-T treatment regimen

6. Adequate renal and hepatic function defined as:

   • Serum alanine aminotransferase (ALT/AST) ≤ 3 upper limit of normal (ULN)
   • Total bilirubin ≤1.5 mg/dL(<3 times ULN in patients with Gilbert's syndrome, cholestasis due to hepatoportal compression adenopathy, biliary obstruction in patients with liver involvement or lymphoma)
   • Serum creatinine ≤1.5 ULN, or creatinine clearance (as estimated by Cockcroft Gault) ≥ 30 mL/min

7. Cardiac ejection fraction ≥ 40%

8. Baseline oxygen saturation > 95% on room air

9. Life expectancy ≥3 months

Exclusion criteria

1. History of autologous or allogeneic stem cell transplantation
2. Active HBV or HCV infection, defined as HBV-DNA or HCV-DNA levels above the normal upper limit, with or without abnormal liver function. Individuals with positive HBsAg or HBcAb should receive antiviral prophylaxis for at least 12 months after CAR-T cells infusion.
3. Presence of uncontrolled infection, cardio-cerebrovascular disease，coagulopathy, or connective tissue disease.
4. History of HIV infection
5. Prior chimeric antigen receptor cellular immunotherapy targeting CD19
6. Pregnant or lactating patients

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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16 participants in 1 patient group

CAR-T following ASCT

Experimental group

Description:

Participants will receive high-dose chemotherapy followed by stem-cell infusion, and a fixed dose of CAR-T cells will be infused.

Treatment:

Other: autologous stem-cell transplantation

Drug: Relmacabtagene autoleucel (relma-cel)