Overview
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
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.
Eligibility
Inclusion Criteria:
- 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)
- 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
- 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
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Eligible for HDCT/ASCT based on the investigator's assessment and are scheduled to undergo an ASCT sequential CAR-T treatment regimen
- 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
- Cardiac ejection fraction ≥ 40%
- Baseline oxygen saturation > 95% on room air
- Life expectancy ≥3 months
Exclusion Criteria:
- History of autologous or allogeneic stem cell transplantation
- 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.
- Presence of uncontrolled infection, cardio-cerebrovascular disease，coagulopathy, or connective tissue disease.
- History of HIV infection
- Prior chimeric antigen receptor cellular immunotherapy targeting CD19
- Pregnant or lactating patients