protocolSection identificationModule nctId: NCT06321289, orgStudyIdInfo id: CHN-PLAGH-BT-084, briefTitle: Allogeneic TRAC Locus-inserted CD19-targeting STAR T Cell Therapy in r/r B-NHL, statusModule overallStatus: RECRUITING, startDateStruct date: 2024-03-20, primaryCompletionDateStruct date: 2026-03-20, completionDateStruct date: 2027-03-20, studyFirstPostDateStruct date: 2024-03-20, lastUpdatePostDateStruct date: 2024-03-25, sponsorCollaboratorsModule leadSponsor name: Chinese PLA General Hospital, class: OTHER, descriptionModule briefSummary: The team has developed the synthetic T cell receptor (TCR) and antigen receptor (STAR) T cells which were demonstrated safety in relapsed or refractory (r/r) B-cell non-Hodgkin' s lymphoma (B-NHL) (NCT05631912). Based on this research, allogeneic STAR-T cell products utilized the CRISPR-Cas9 gene editing tool to knock out endogenous receptor α constant (TRAC), human leukocyte antigen (HLA)-A/B, CIITA, and programmed death 1 (PD-1) genes simultaneously in T cells from healthy donors, and integrated the STAR molecule into the TRAC locus using adenovirus associated virus. This strategy can reduce graft-versus-host-disease (GvHD) toxicity and host-versus-graft response, decrease the sensitivity of STAR T cells to immunosuppressive signals, and improve their anti-tumor activity. In this single center, prospective, open-label, single-arm, phase 1/2 study, the safety and efficacy of allogeneic CD19-targeting STAR T cell therapy will be evaluated in patients with r/r B-NHL., conditionsModule conditions: Non-hodgkin Lymphoma,B Cell, designModule studyType: INTERVENTIONAL, phases: PHASE1, phases: PHASE2, designInfo allocation: NA, interventionModel: SEQUENTIAL, primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 30, type: ESTIMATED, armsInterventionsModule interventions name: Allogeneic CD19-STAR T cell, interventions name: Fludarabine, interventions name: Cyclophosphamide, outcomesModule primaryOutcomes measure: Phase 1: Incidence of Adverse Events (AEs) defined as DLT, primaryOutcomes measure: Phase 1: RP2D, primaryOutcomes measure: Phase 2: Best objective Response Rate, secondaryOutcomes measure: Phase 2: Overall Survival (OS), secondaryOutcomes measure: Phase 2: Progression Free Survival (PFS), secondaryOutcomes measure: Phase 2: Time to response (TTR), secondaryOutcomes measure: Phase 2: Duration of Response (DOR), secondaryOutcomes measure: Pharmacokinetics: Number and copy number of CD19-STAR T cells (phase 1 and phase 2), secondaryOutcomes measure: Pharmacokinetics: Persistence of CD19-STAR T (phase 1 and phase 2), secondaryOutcomes measure: Pharmacodynamics: Peak level of cytokines in serum (phase 1 and phase 2), otherOutcomes measure: Phase 1: Levels of donor-specific anti-HLA antibodies (DSA) in blood., eligibilityModule sex: ALL, minimumAge: 18 Years, maximumAge: 75 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: Biotherapeutic Department of Chinese PLA General Hospital, status: RECRUITING, city: Beijing, state: Beijing, zip: 100853, country: China, contacts name: Weidong Han, M.D, role: CONTACT, phone: +86-010-66937463, email: hanwdrsw@sina.com, contacts name: Qingming Yang, M.D, role: SUB_INVESTIGATOR, contacts name: Yang Liu, M.D, role: SUB_INVESTIGATOR, contacts name: Jinhong Shi, M.S, role: SUB_INVESTIGATOR, contacts name: Chunmeng Wang, M.S, role: SUB_INVESTIGATOR, geoPoint lat: 39.9075, lon: 116.39723, locations facility: School of medicine, Tsinghua University & Changping Laboratory, status: RECRUITING, city: Beijing, country: China, contacts name: Xin Lin, Ph.D, role: CONTACT, phone: +86-010-62796319, email: linxin307@mail.tsinghua.edu.cn, contacts name: Xin Lin, Ph.D, role: SUB_INVESTIGATOR, geoPoint lat: 39.9075, lon: 116.39723, hasResults: False