CMV-TCR-T Cells for CMV Infection After Allogenic HSCT
- Conditions
- CMV Infection After Allogenic HSCT
- Interventions
- Biological: CMV-TCR-T cells
- Registration Number
- NCT05140187
- Lead Sponsor
- Chinese PLA General Hospital
- Brief Summary
This is a multi-center, single arm, open-label, phase I study to determine the safety and effectiveness of CMV-TCR-T cell immunotherapy in treating CMV virus infection after allogenic HSCT.
- Detailed Description
Cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (HSCT) is common and can be lethal without prompt treatment. In this prospective study, HLA-A\*02:01/11:01/24:02-restricted CMV-specific T cell receptor (TCR) will be introduced into the T cells of HSCT donors by ex vivo lentiviral transduction to generate CMV-TCR-T cells. An escalated dose ranging from 1×10\^3/kg to 5×10\^5/kg of CMV-TCR-T cells will be infused into patients with CMV infection. The safety, efficacy, pharmacokinetics and cytokine levels of allogenic CMV-TCR-T cell therapy will be evaluated.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 12
- Age 1-60 years, gender unlimited.
- Diagnosed with hematologic malignancies and have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT), with CMV infection after allo-HSCT.
- Karnofsky Score ≥ 70 or Lansky Score ≥ 50.
- TCR-T cell donor inclusion criteria:
- Age ≥ 8 years; 2) Understand and voluntarily sign informed consent and are willing to comply with laboratory tests and other research procedures; 3) ≥ 3/6 HLA match with TCR-T cell recipients enrolled; 4) Lymphocyte count = (0.8~4) × 10^9/L; 5) Have sufficient venous circulation, without any symptoms that do not allow blood cell isolation.
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Patients with active aGVHD one day before TCR-T cell infusion.
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Patients with severe kidney disease (Cr > 3×normal value), liver damage (TBIL >2.5×upper limit of normal value, ALT and AST > 3×upper limit of normal value) or heart failure (NYHA heart function grade IV) one week before TCR-T cell infusion.
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Anticipated to take immunosuppressive hormones on the day of TCR-T cell infusion.
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Have other malignancies.
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Have relapsed and uncontrolled hematologic malignancies.
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Serologically positive for HIV-Ab or TAP-ab.
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Pregnant or lactating women.
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Anticipated to have other cell therapies in 4 week post TCR-T cell infusion.
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Participated in any other clinical study of drugs and medical devices before 30 days of enrollment.
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Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.
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TCR-T cell donor exclusion criteria:
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Positive for any of the following: HbsAg, HBeAg, HBV-DNA, HCV-Ab, HCV-RNA, HIV-Ab, TP-Ab, EBV-DNA or CMV-DNA;
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Other uncontrolled infection;
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Have taken immunosuppressive drugs 1 week before PBMC collection;
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Any condition that would, in the investigator's judgment, make it unsuitable for the donors to be enrolled.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description CMV-TCR-T cells CMV-TCR-T cells The patients with CMV infection after HSCT will receive one to three infusions of donor-derived CMV-TCR-T cells, with the escalated dose ranging from 1×10\^3/kg to 5×10\^5/kg CMV-TCR-T cells per dose.
- Primary Outcome Measures
Name Time Method Adverse events 1 year Percentage of participants with adverse events.
- Secondary Outcome Measures
Name Time Method Changes of CMV-DNA copies number 1 year Quantitative PCR will be used to determine viral copy numbers in peripheral blood.
Persistence of CMV-TCR-T cells 1 year Quantitative PCR using primers specific for the gene encoding CMV-TCR will be used to determine the number of circulating CMV-TCR-T cells in peripheral blood post infusion.
Trial Locations
- Locations (1)
Chinese PLA General Hospital
🇨🇳Beijing, Beijing, China