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The primary consideration is the allocation of company resources, and we have no choice but to terminate this research.
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This is a single-arm, open-label clinical study evaluating the efficacy and safety of CD20/CD19/CD22 multi-targeted chimeric antigen receptor T-cell (CAR-T) injection in patients with relapsed/refractory B-cell lymphoma.
The primary objective of this study is to assess the safety and efficacy of CD19/CD20/CD22 muti-target CAR-T therapy in patients with relapsed or refractory B-cell lymphoma.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Multi-targeted CAR-T Therapy | Experimental | Patients will receive a regimen combining CD19/CD22 dual-targeted CAR-T cells with CD19/CD20 dual-targeted CAR-T cells; investigators may administer them sequentially according to each patient's condition. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Triple-targeted CAR-T Therapy | Drug | Lymphodepletion preconditioning is required prior to CAR-T cell therapy. Lymphodepletion will be performed using a regimen of cyclophosphamide (250-500 mg/m²) and fludarabine (25-30 mg/m²), each administered for 3 consecutive days. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Adverse events after CAR-T cells infusion [Safety and Tolerability] | An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) | 28 days post administration of CAR-T-cells |
| Objective Response Rate (ORR), as assessed by Investigators | The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Remission (CR) or Partial Remission (PR) | 2 years post CAR T cell infusion |
| Duration of response (DOR), as assessed by Investigators | Duration of response (DOR) is defined as the time from the first documented objective response to the first documented disease progression or death. | 2 years post CAR T cell infusion |
| Progression-free survival (PFS), as assessed by Investigators | Progression-free survival (PFS) was defined as the time from the date of infusion to the earliest date of the first objective documentation of progressive disease (PD) or death due to any cause. | 2 years post CAR T cell infusion |
| Overall survival (OS) | Overall Survival (OS) was defined as the time from the date of first infusion to the date of death due to any cause. | 2 years post CAR T cell infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics of CAR-T cells | Time at the maximal concentration(Tmax) | 2 years post CAR T cell infusion |
| Pharmacokinetics of CAR-T cells | Area under the concentration-time curve(AUC) |
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Inclusion Criteria:
Voluntary written informed consent obtained from the participant (or legally authorized representative) with good compliance expected throughout the study.
All of the following must be fulfilled:
Age 2-75 years at the time of informed consent; both sexes eligible.For minors (≤18 years), consent must be provided by a parent or legal guardian; minors who are able to sign must co-sign with their guardian.
Histologically confirmed B-cell lymphoma according to the NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas (2024 v3).
Relapsed or refractory B-cell lymphoma after at least two prior lines of therapy (one standard chemo-regimen + one salvage regimen) that must have included:
Subjects must additionally meet at least one of the following:
i. Ineligible for autologous hematopoietic stem-cell transplantation (ASCT); ii. Refusal of ASCT; iii. Relapse after ASCT. d) Disease status at screening:
• Relapse: progression after prior response (PR or CR).
• Refractory: i. No response to last therapy (progressive disease [PD] during/after, or best response ≤SD lasting <6 months); OR ii. Relapse or progression after ASCT (biopsy-proven) including: relapse/PD ≤12 months post-ASCT, or relapse/PD after salvage therapy post-ASCT without response (SD or PD).
Tumor tissue (archival or fresh biopsy) positive for CD20 and/or CD19 and/or CD22 by immunohistochemistry (pathology report within 6 months preferred).
≥1 measurable lesion per Lugano 2014 (Cheson) criteria.
ECOG performance status 0-3.
Adequate marrow reserve at screening:Absolute lymphocyte count (ALC) ≥0.3 × 10⁹/L; Platelets ≥30 × 10⁹/L (transfusion permitted).
Adequate organ function:AST ≤3×ULN (≤5×ULN if attributable to tumor infiltration); ALT ≤3×ULN (≤5×ULN if attributable to tumor infiltration); Total bilirubin ≤2×ULN (≤3×ULN with direct bilirubin ≤1.5×ULN for Gilbert's syndrome); Serum creatinine ≤1.5×ULN or creatinine clearance ≥60 mL/min (Cockcroft-Gault); Pulmonary reserve: ≤Grade 1 dyspnea and SpO₂ >91 % on room air; LVEF ≥50 % by echocardiography; INR ≤1.5×ULN and APTT ≤1.5×ULN.
Women of child-bearing potential must have a negative serum/urine pregnancy test within 7 days before CAR-T infusion. All participants with reproductive potential must use effective contraception from screening through at least 12 months after the last CAR-T dose.
Adequate venous access for leukapheresis or repeated phlebotomy, with no contraindications to leukapheresis.
Anticipated survival ≥3 months.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Junfang Yang, Ph.D. | Hebei Yanda Ludaopei Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hebei Yanda Ludaopei Hospital | Hebei | China | ||||
| Tongji Hospital of Tongji University |
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| ID | Term |
|---|---|
| D016393 | Lymphoma, B-Cell |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| 2 years post CAR T cell infusion |
| Pharmacokinetics of CAR-T cells | The maximal concentration of peripheral blood (Cmax) | 2 years post CAR T cell infusion |
| Pharmacodynamics of CAR-T cells | Concentration levels of CAR-T-related serum cytokines such as IL-6, IFN γ, ferritin and CRP at each time point | 2 years post CAR T cell infusion |
| Shanghai |
| China |
| D008232 |
| Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |