CMV-TCR-T Cells for CMV Infection After Allogenic HSCT

Chinese PLA General Hospital (301 Hospital)

Status and phase: Enrolling; Phase 1

Conditions: CMV Infection After Allogenic HSCT

Treatments: Biological: CMV-TCR-T cells

Study type: Interventional

Funder types: Other

Identifiers

NCT05140187

S2021-344-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 12 estimated patients

Sex: All

Ages: 1 to 60 years old

Volunteers: No Healthy Volunteers

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.

10. 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.

11. TCR-T cell donor exclusion criteria:

12. Positive for any of the following: HbsAg, HBeAg, HBV-DNA, HCV-Ab, HCV-RNA, HIV-Ab, TP-Ab, EBV-DNA or CMV-DNA;

13. Other uncontrolled infection;

14. Have taken immunosuppressive drugs 1 week before PBMC collection;

15. Any condition that would, in the investigator's judgment, make it unsuitable for the donors to be enrolled.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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12 participants in 1 patient group

CMV-TCR-T cells

Experimental group

Description:

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.

Treatment:

Biological: CMV-TCR-T cells