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

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

NCT ID: NCT06365671

Condition: B-cell Non Hodgkin Lymphoma

Conditions: Official terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Other
Intervention name: autologous stem-cell transplantation
Description: high-dose chemotherapy and autologous stem-cell transplantation (HDT/ASCT)
Arm group label: CAR-T following ASCT

Intervention type: Drug
Intervention name: Relmacabtagene autoleucel (relma-cel)
Description: relma-cel (CD19 CAR-T cell)infusion on day 3(±1d) after ASCT with a fixed dose of 100X10^6.
Arm group label: CAR-T following ASCT

Summary: 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

Detailed description: This is a single-center, single-arm, open-label, prospective clinical trial to evaluate the efficacy and safety of Relmacabtagene autoleucel (relma-cel) 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). Relma-cel 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.

Criteria for eligibility:
Criteria:
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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Address:
City: Shanghai
Country: China

Status: Recruiting

Contact:
Last name: Weili Zhao
Email: zwl_trial@163.com

Start date: April 16, 2024

Completion date: April 2027

Lead sponsor:
Agency: Ruijin Hospital
Agency class: Other

Source: Ruijin Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06365671