CMV-TCR-T Cells for CM Virus Infection After HSCT

Study Overview
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Brief Summary
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This is a single cente, single arm, open-label, phase I study to evaluate the safety and effectiveness of CMV-TCR-T cell immunotherapy in treating CMV virus infection after HSCT.

Detailed Description
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CMV infection is a common virus infection of HSCT, and which is highly related with the failure of transplantation and survival time of transplant patients. To evaluate the safety and efficacy of allogenic CMV-TCR-T cell therapy in subjects with CMV infection, patients with CMV emias or deseases will be enrolled, and donor derived CMV-TCR-T(HLA-A*1101\0201\2402) cells will be intravenously infused with a escalated dose of 0.1-1×106 CMV-TCR-T cells. The CMV DNA copies and CMV-TCR-T cell proliferation will be monitored in the scheduled time (day 0, day 4, day 7, day 10, day 14, day 28).

Official Title
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A Pilot Study of CMV-TCR-T Cells in CM Virus Infection Diseases After HSCT

Conditions
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CMV Infection or Reactivation After Allogenic HSCT

Intervention / Treatment
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* Biological: CMV-TCR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 1-70 years, including boundary values, gender unlimited; Allogenic hematopoietic stem cell transplantation patients with CMV infection disease or persistent CMV emia; At least one of the following conditions after allogeneic HSCT: After trested with 2-week standard antiviral drug, compared to the baseline of treatment, the decrease of CMV DNA copies number was less than 1log10, and the CMV DNA copies number is greater than 1000 copies/ mL ; Unable to tolerate the toxic and side effects of antiviral drugs,such as bone marrow hematopoietic suppression, nephrotoxicity; Estimated life expectancy ≥3 months； ECOG 3; Patients who voluntarily sign informed consent and are willing to comply with treatment plans, visit arrangements, laboratory tests and other research procedures. Exclusion Criteria: Patients with active aGVHD III-IV and / or mild and severe cGVHD; Received cell therapy such as DLI,CTL,CAR-T or participated in any other clinical study of drugs and medical devices before 30 days of enrollment. Pregnant or lactating women; Intracranial hypertension or confusion; respiratory failure; disseminated intravascular coagulation; patients with organ failure: Heart: NYHA heart function grade IV; Liver: Grade C that achieves Child-Turcotte liver function grading; Kidney: kidney failure and uremia; Lung: symptoms of respiratory failure; Brain: a person with a disability; The researchers found that it was unsuitable for the recipients to be enrolled.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CMV-TCR-T cells<br>The patients will receive one dose of CMV-TCR-T.The dosage ranges from 0.1×10^6 to 1×10^6 TCR+T/Kg. | Biological: CMV-TCR-T cells<br>* Patients with CMV emias or CMV disease will be enrolled, and donor derived CMV-TCR-T(HLA-A*1101\0201\2402) cells will be intravenously infused with a escalated dose of 0.1-1×106 CMV-TCR-T cells. The CMV DNA copies and CMV-TCR-T cell proliferation will be monitored in the scheduled time (day 0, day 4, day 7, day 10, day 14,day 28).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of adverse events | Percentage of participants with adverse events. | 3months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistence of TCR-T cells |  | 3months | 
| Changes of CMV-DNA copies number |  | 3months |