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 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).
調査の概要
状態
募集
条件
研究の種類
介入
入学 (推定)
70
段階
- フェーズ2
- フェーズ 1
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Wenbin Qian,Professor
- 電話番号：+86 13605801032
- メール：qianwb@zju.edu.cn
研究連絡先のバックアップ
- 名前：Wen Lei,Doctor
- 電話番号：+86 18258448016
- メール：leiwen2017@zju.edu.cn
研究場所
-
-
Zhejiang
-
Hangzhou、Zhejiang、中国、310009
- 募集
- The Second Affiliated Hospital,School of Medicine,Zhejiang University, Hangzhou, Zhejiang 310009
-
コンタクト：
- Wenbin Qian,Professor
- 電話番号：+86 13605801032
- メール：qianwb@zju.edu.cn
-
コンタクト：
- Wen Lei,Doctor
- 電話番号：+86 18258448016
- メール：leiwen2017@zju.edu.cn
-
-
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
いいえ
説明
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).
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：7×19-THEMIS CAR-T
A single dose intravenous injection of 7X19-Themis at day 0
|
IL7 and CCL19 Armed anti-CD19 CAR-T with coexpressing Themis
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Determination of the Recommended Phase II Dose (RP2D)
時間枠：Up to 3 months
|
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
|
|
Objective Response Rate (ORR)
時間枠：Up to 3 months
|
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.
|
Up to 3 months
|
|
Complete Remission Rate (CR Rate)
時間枠：Up to 3 months
|
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.
|
Up to 3 months
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) graded according to ASTCT 2019 criteria
時間枠：up to 28 days
|
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.
|
up to 28 days
|
|
Incidence and duration of Grade ≥3 hematologic toxicities assessed according to CTCAE version 5.0
時間枠：up to 28 days
|
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.
|
up to 28 days
|
|
Incidence of clinically significant infections requiring anti-infective treatment or hospitalization
時間枠：up to 28 days
|
The incidence of bacterial, fungal, and viral infections requiring anti-infective treatment or hospitalization will be recorded and summarized.
|
up to 28 days
|
|
Progression-Free Survival (PFS)
時間枠：up to 2-5 years
|
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.
|
up to 2-5 years
|
|
Overall Survival (OS)
時間枠：up to 2-5 years
|
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.
|
up to 2-5 years
|
|
Duration of Response (DOR)
時間枠：up to 2-5 years
|
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.
|
up to 2-5 years
|
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In Vivo Kinetics of CAR-T Cells
時間枠：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
時間枠：day-5,day4,day7,day11,day14,day18,day21,day28,month 3
|
Measure the concentrations of cytokines such as IL-6, IFN-γ, IL-7, and CCL19 in serum at various time points following infusion.
|
day-5,day4,day7,day11,day14,day18,day21,day28,month 3
|
|
B-Cell Recovery
時間枠：month1, month3, month6, month9, months12, month24, year3 and year5
|
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
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Single-Cell Functional Characterization of CAR-T Products
時間枠：day-5, day4, day7, day11, day14, day18, day21, day28, month2
|
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
|
|
Spearman correlation between memory T-cell subset proportions in the CAR-T infusion product and 3-month complete response
時間枠：day-5, day4, day7, day11, day14, day18, day21, day28, month3
|
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.
|
day-5, day4, day7, day11, day14, day18, day21, day28, month3
|
|
Trends in Anti-CAR Antibodies (ADA)
時間枠：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
|
day-5, day4, day7, day11, day14, day18, day21, day28, month3,month6,month12, year2 and year5
|
|
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
時間枠：month6, month12, year2, year5
|
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.
|
month6, month12, year2, year5
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
捜査官
- スタディチェア：Wenbin Qian,Professor、Second Affiliated Hospital, Zhejiang University, School of Medicine
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (推定)
2026年9月1日
一次修了 (推定)
2029年9月1日
研究の完了 (推定)
2031年9月1日
試験登録日
最初に提出
2026年8月12日
QC基準を満たした最初の提出物
2026年8月23日
最初の投稿 (実際)
2026年8月26日
学習記録の更新
投稿された最後の更新 (実際)
2026年8月26日
QC基準を満たした最後の更新が送信されました
2026年8月23日
最終確認日
2026年8月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 2026-0675
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
いいえ
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米国FDA規制医薬品の研究
いいえ
米国FDA規制機器製品の研究
いいえ
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