CMV Infection After Allogenic HSCT
Conditions
Keywords
CMV, HSCT
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.
Interventions
BIOLOGICALCMV-TCR-T cells
The patients with CMV infection after HSCT will receive one to three doses of donor-derived CMV-TCR-T cells, with the escalated doses including 1×10\^3/kg, 1×10\^5/kg, and 5×10\^5/kg CMV-TCR-T cells per dose.
Sponsors
Chinese PLA General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Age 1-60 years, gender unlimited. 2. Diagnosed with hematologic malignancies and have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT), with CMV infection after allo-HSCT. 3. Karnofsky Score ≥ 70 or Lansky Score ≥ 50. 4. TCR-T cell donor inclusion criteria: 1\) 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.
Exclusion criteria
1. Patients with active aGVHD one day before TCR-T cell infusion. 2. 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. 3. Anticipated to take immunosuppressive hormones on the day of TCR-T cell infusion. 4. Have other malignancies. 5. Have relapsed and uncontrolled hematologic malignancies. 6. Serologically positive for HIV-Ab or TAP-ab. 7. Pregnant or lactating women. 8. Anticipated to have other cell therapies in 4 week post TCR-T cell infusion. 9. Participated in any other clinical study of drugs and medical devices before 30 days of enrollment. 11\. 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. 12\. TCR-T cell donor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | 1 year | Percentage of participants with adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
China
Contacts
Primary ContactDaihong Liu
Backup ContactLiping Dou
Outcome results
None listed