A Phase Ib/II Exploratory Clinical Trial of Memory-Enhanced 7×19-THEMIS CAR-T Cell Therapy for Relapsed/Refractory Large B-Cell Lymphoma
2026년 8월 23일 업데이트: Second Affiliated Hospital, Zhejiang University, School of Medicine
A Phase Ib/II Exploratory Clinical Trial of Memory-Enhanced 7×19-THEMIS CAR-T Cell Therapy for Relapsed/Refractory Large B-Cell Lymphoma: A Single-Arm Design Using a Historical Control (7×19 CAR-T)
This study is aimed to explored the safety and efficacy of 7×19-THEMIS CAR-T cell therapy for large B-cell lymphoma and to conduct an exploratory comparison of the 3-month objective response rate (ORR) and complete remission rate (CR rate) between the experimental cohort and the historical control cohort (NCT04833504).
연구 개요
상태
모병
정황
개입 / 치료
연구 유형
중재적
등록 (추정된)
70
단계
- 2 단계
- 1단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 연락처
- 이름: Wenbin Qian,Professor
- 전화번호: +86 13605801032
- 이메일: qianwb@zju.edu.cn
연구 연락처 백업
- 이름: Wen Lei,Doctor
- 전화번호: +86 18258448016
- 이메일: leiwen2017@zju.edu.cn
연구 장소
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Zhejiang
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Hangzhou, Zhejiang, 중국, 310009
- 모병
- The Second Affiliated Hospital,School of Medicine,Zhejiang University, Hangzhou, Zhejiang 310009
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연락하다:
- Wenbin Qian,Professor
- 전화번호: +86 13605801032
- 이메일: qianwb@zju.edu.cn
-
연락하다:
- Wen Lei,Doctor
- 전화번호: +86 18258448016
- 이메일: leiwen2017@zju.edu.cn
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-
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
아니
설명
Inclusion Criteria:
- Voluntarily participate in this study and sign the informed consent form.
- Age range: 18 - 75 years old. Gender is not restricted.
- Histologically confirmed large B-cell lymphoma, including: diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), transformed follicular lymphoma (tFL), and mantle cell lymphoma (MCL).
- CD19-positive (as determined by immunohistochemistry or flow cytometry; based on the most recent tumor biopsy results).
- Definition of relapsed/refractory: Failure to achieve complete remission (CR) after at least two lines of therapy (which must include a CD20 monoclonal antibody and an anthracycline); or disease progression during any course of treatment; or relapse/progression within 12 months after autologous hematopoietic stem cell transplantation.
- At least one measurable lesion: any lymph node lesion with a longest dimension >1.5 cm, or any extranodal lesion with a longest dimension >1.0 cm, and the lesion shows uptake on PET-CT (SUV greater than the hepatic pool).
- Absolute neutrophil count in peripheral blood ≥ 1,000/μL; platelet count ≥ 45,000/μL.
- Cardiac, hepatic, and renal function: creatinine < 1.5 mg/dL; ALT/AST ≤ 2.5 times the upper limit of normal; total bilirubin < 1.5 mg/dL; ejection fraction ≥ 50%.
- Possess sufficient cognitive capacity to voluntarily sign the informed consent form.
- Participants of reproductive potential must be willing to use effective contraception (from the time of signing the informed consent form until 12 months after CAR-T infusion).
- The investigator estimates a life expectancy of at least 4 months.
- Willing to comply with the schedule of visits, dosing regimen, laboratory tests, and other trial procedures.
Exclusion Criteria:
- History of other malignant tumors (excluding cured basal cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma, etc.).
- Autologous hematopoietic stem cell transplantation within the past 6 weeks.
- Any targeted CAR-T therapy within 3 months prior to this CAR-T treatment.
- Patients who have previously received PD-1 monoclonal antibodies must have a washout period of ≥3 months before enrollment.
- Received cytotoxic drugs, glucocorticoids (except for prednisone-equivalent doses of ≤10 mg/day), or other targeted therapies within 2 weeks prior to cell collection.
- Active autoimmune diseases (e.g., systemic lupus erythematosus, inflammatory bowel disease, etc.).
- Uncontrolled active bacterial, fungal, or viral infections.
- HIV infection, syphilis; active hepatitis B or C: Hepatitis B: HBsAg-positive and HBV-DNA ≥ 1,000 IU/mL; Hepatitis C: HCV RNA-positive and abnormal liver function.
- Known central nervous system lymphoma (confirmed by brain MRI or CT and cerebrospinal fluid examination).
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: 7×19-THEMIS CAR-T
A single dose intravenous injection of 7X19-Themis at day 0
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IL7 and CCL19 Armed anti-CD19 CAR-T with coexpressing Themis
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Determination of the Recommended Phase II Dose (RP2D)
기간: Up to 3 months
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Based on the incidence of DLTs, CAR-T cell kinetics, preliminary efficacy, and safety data from the Phase Ib dose-escalation phase, the Safety Review Committee (SRC) determined the RP2D following a comprehensive evaluation.
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Up to 3 months
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Objective Response Rate (ORR)
기간: Up to 3 months
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At 3 months (±7 days) after infusion, the proportion of patients achieving complete remission (CR) or partial remission (PR) was assessed according to the Lugano 2014 criteria, and a descriptive comparison was made with the historical control cohort.
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Up to 3 months
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Complete Remission Rate (CR Rate)
기간: Up to 3 months
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At 3 months (±7 days) after infusion, the proportion of patients who achieved complete remission (CR) was assessed according to the Lugano 2014 criteria, and a descriptive comparison was made with the historical control cohort.
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Up to 3 months
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) graded according to ASTCT 2019 criteria
기간: up to 28 days
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The incidence and severity of CRS and ICANS will be assessed according to the American Society for Transplantation and Cellular Therapy (ASTCT) 2019 consensus grading criteria.
The incidence of each grade (Grades 1-4) will be summarized, with particular attention to the incidence of Grade ≥3 CRS and Grade ≥3 ICANS.
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up to 28 days
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Incidence and duration of Grade ≥3 hematologic toxicities assessed according to CTCAE version 5.0
기간: up to 28 days
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The incidence and duration of Grade ≥3 neutropenia, anemia, and thrombocytopenia will be assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
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up to 28 days
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Incidence of clinically significant infections requiring anti-infective treatment or hospitalization
기간: up to 28 days
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The incidence of bacterial, fungal, and viral infections requiring anti-infective treatment or hospitalization will be recorded and summarized.
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up to 28 days
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Progression-Free Survival (PFS)
기간: up to 2-5 years
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Progression-free survival is defined as the time from CAR-T cell infusion to the first documented disease progression (PD) or death from any cause, whichever occurs first.
Median PFS and PFS rates at 12 and 24 months will be estimated using the Kaplan-Meier method.
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up to 2-5 years
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Overall Survival (OS)
기간: up to 2-5 years
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Overall survival is defined as the time from CAR-T cell infusion to death from any cause.
Median OS and OS rates at 12 and 24 months will be estimated using the Kaplan-Meier method.
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up to 2-5 years
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Duration of Response (DOR)
기간: up to 2-5 years
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Among participants who achieve complete response (CR) or partial response (PR), duration of response is defined as the time from the first documented response to disease progression or death from any cause, whichever occurs first.
Median DOR will be estimated using the Kaplan-Meier method.
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up to 2-5 years
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In Vivo Kinetics of CAR-T Cells
기간: up to 2-5 years
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Measurement of CAR-T Cell Counts in Peripheral Blood and Comparison of Kinetic Parameters
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up to 2-5 years
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Serum Cytokine Dynamics
기간: day-5,day4,day7,day11,day14,day18,day21,day28,month 3
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Measure the concentrations of cytokines such as IL-6, IFN-γ, IL-7, and CCL19 in serum at various time points following infusion.
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day-5,day4,day7,day11,day14,day18,day21,day28,month 3
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B-Cell Recovery
기간: month1, month3, month6, month9, months12, month24, year3 and year5
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Determine the absolute count of CD19+CD20+ cells in peripheral blood to assess the dynamics of B-cell recovery following infusion.
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month1, month3, month6, month9, months12, month24, year3 and year5
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기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Single-Cell Functional Characterization of CAR-T Products
기간: day-5, day4, day7, day11, day14, day18, day21, day28, month2
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Detection of various cytokines secreted by CAR-T infusion products at the single-cell level upon stimulation with the CD19 antigen.
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day-5, day4, day7, day11, day14, day18, day21, day28, month2
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Spearman correlation between memory T-cell subset proportions in the CAR-T infusion product and 3-month complete response
기간: day-5, day4, day7, day11, day14, day18, day21, day28, month3
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The proportions of stem cell memory T cells (TSCM), central memory T cells (TCM), effector memory T cells (TEM), and terminal effector T cells (TTE) in the CAR-T infusion product will be measured by multicolor flow cytometry.
T-cell subsets will be defined as TSCM (CD45RA+CCR7+CD95+), TCM (CD45RA-CCR7+), TEM (CD45RA-CCR7-), and TTE (CD45RA+CCR7-).
The proportion of each subset will be expressed as the percentage of CAR-T cells.
The correlation between memory T-cell subset proportions and complete response at 3 months will be assessed using Spearman rank correlation and exploratory group comparisons using the Mann-Whitney U test.
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day-5, day4, day7, day11, day14, day18, day21, day28, month3
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Trends in Anti-CAR Antibodies (ADA)
기간: day-5, day4, day7, day11, day14, day18, day21, day28, month3,month6,month12, year2 and year5
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Determination of the Prevalence and Titer of Anti-FMC63 Antibodies (ADA) in Serum
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day-5, day4, day7, day11, day14, day18, day21, day28, month3,month6,month12, year2 and year5
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Area under the receiver operating characteristic curve (AUC) of peak serum cytokine and chemokine levels within 28 days after CAR-T infusion for discrimination of objective response
기간: month6, month12, year2, year5
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Peak serum concentrations of IL-7, CCL19, MIP-1α, MIP-1β, and SDF-1α during the first 28 days after CAR-T cell infusion will be measured using the protocol-specified serum cytokine/chemokine assay.
Receiver operating characteristic (ROC) curve analysis will be performed to evaluate the ability of each biomarker to discriminate objective response, defined as complete response or partial response according to protocol-defined disease response criteria.
The AUC and the optimal biomarker cutoff value will be determined for each biomarker.
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month6, month12, year2, year5
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
수사관
- 연구 의자: Wenbin Qian,Professor, Second Affiliated Hospital, Zhejiang University, School of Medicine
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (추정된)
2026년 9월 1일
기본 완료 (추정된)
2029년 9월 1일
연구 완료 (추정된)
2031년 9월 1일
연구 등록 날짜
최초 제출
2026년 8월 12일
QC 기준을 충족하는 최초 제출
2026년 8월 23일
처음 게시됨 (실제)
2026년 8월 26일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2026년 8월 26일
QC 기준을 충족하는 마지막 업데이트 제출
2026년 8월 23일
마지막으로 확인됨
2026년 8월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- 2026-0675
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
아니요
약물 및 장치 정보, 연구 문서
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미국 FDA 규제 기기 제품 연구
아니
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .