A Study of Automated Axicabtagene Ciloleucel for R/R Large B-cell Lymphoma.

Official title

A Single-arm, Multicenter Clinical Study Evaluating the Efficacy and Safety of Axicabtagene Ciloleucel Injection Manufactured by an Automated Process in Patients With Relapsed/Refractory Large B-cell Lymphoma.

Overview

This study is a single-arm, multicenter, open-label clinical study evaluating the efficacy and safety of axicabtagene ciloleucel injection manufactured by an automated cell preparation process in adult subjects with relapsed or refractory large B-cell lymphoma (r/r LBCL) as second-line therapy.

Detailed description

This study is a single-arm, multicenter, open-label clinical study evaluating the efficacy and safety of axicabtagene ciloleucel injection manufactured by an automated cell preparation process in adult subjects with relapsed or refractory large B-cell lymphoma (r/r LBCL) as second-line therapy. A total of 12 adult subjects with r/r LBCL who are refractory to first-line immunochemotherapy or who relapse within 12 months after first-line immunochemotherapy will be enrolled. All subjects will undergo leukapheresis, bridging therapy, conditioning chemotherapy, and a single study drug infusion.

Interventions

• Drug FKC876 injection
  CD19 CAR-T

Primary outcome measures

• Objective response rate (ORR) [Time frame: Up to 24 months]

Secondary outcome measures (4)

• Complete response rate (CRR) [Time frame: Within 6 months,12 months, and 24 months after FKC876 infusion]
• Duriation of response (DOR) [Time frame: Up to 24 months]
• Progression-frees survival (PFS) [Time frame: Up to 24 months]
• Overall survival(OS) [Time frame: Up to 24 months]

Eligibility criteria

Inclusion criteria

• Age 18 years or older at the time of informed consent
• Has signed the informed consent form (ICF)
• Histologically proven large B-cell lymphoma
• Relapsed or refractory disease after first-line chemoimmunotherapy
• The subject has at least one measurable lesion on imaging
• No clinical or historical evidence suggestive of lymphoma involvement of the central nervous system (CNS)
• A washout period of at least 2 weeks or 5 half-lives (whichever is shorter) from the last prior systemic therapy to the signing of the informed consent form.
• Toxicities due to prior therapy must be stable or recovered to ≤ Grade 1
• ECOG performance status of 0 or 1
• Adequate bone marrow, renal, hepatic, pulmonary and cardiac function
• Female subjects of childbearing potential must have a negative serum pregnancy test . Male and female subjects of childbearing potential must agree to use highly effective contraception during the study and for 6 months post-infusion.

Exclusion criteria

• Prior history of other malignancies, with the exception of non-melanoma skin tumors, carcinoma in situ , or follicular lymphoma that have been free of recurrence for more than 3 years.
• History of Richter's transformation of CLL or PMBCL
• History of autologous or allogeneic stem cell transplant
• Received more than one line of therapy for DLBCL
• Treatment with systemic immunostimulatory agents within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to the first dose of axicabtagene ciloleucel
• Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy
• History of severe, immediate hypersensitivity reaction attributed to aminoglycosides or Tocilizumab
• Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management
• Known history of infection with human immunodeficiency virus (HIV) or Positive test result for anti-Treponema pallidum antibody (TP-Ab) or hepatitis B(HBsAg positive) or hepatitis C virus (anti-HCV positive)
• Active tuberculosis
• Presence of any indwelling line or drain
• Subjects with detectable malignant cells in the cerebrospinal fluid (CSF) or known brain metastases or with a history of cerebrospinal fluid malignant cells or brain metastases
• History or presence of non-malignant CNS disorder
• Subjects with cardiac atrial or cardiac ventricular lymphoma involvement
• History of clinically significant cardiac disease within 12 months of enrollment
• Requirement for urgent therapy within 6 weeks due to tumor mass effects, such as bowel obstruction or blood vessel compression or airway obstruction
• Patients with idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on chest CT are excluded.
• History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment
• Women of childbearing potential who are pregnant or breastfeeding
• In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 6 centers

• Beijing Cancer Hospital — Beijing
• Sun Yat-sen University Cancer Center — Guangzhou
• The Frist Affiliated Hospital of Soochow University — Suzhou
• Shanghai Jiaotong University School of Medicine Ruijin Hospital — Shanghai
• West China Hospotal Sichuan University — Chengdu
• Tianjin Medical University Cancer Institute & Hospital — Tianjin

Identifiers

NCT: NCT07606937 · FKC876-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗