Clinical trial NCT05140187: CMV-TCR-T Cells for CMV Infection After Allogenic HSCT
Official title: Adoptive Immunotherapy With Donor-derived CMV-TCR-T Cells for Patients With CMV Infection After Allogenic HSCT
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: CMV Infection After Allogenic HSCT
Keywords: CMV
HSCT
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2021-12-01
Enrollment: 12
Sex: ALL
Minimum age (years): 1
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 exclusion criteria:

1. Positive for any of the following: HbsAg, HBeAg, HBV-DNA, HCV-Ab, HCV-RNA, HIV-Ab, TP-Ab, EBV-DNA or CMV-DNA;
2. Other uncontrolled infection;
3. Have taken immunosuppressive drugs 1 week before PBMC collection;
4. Any condition that would, in the investigator's judgment, make it unsuitable for the donors to be enrolled.

Primary outcomes:
measure: Adverse events
timeFrame: 1 year
Secondary outcomes:
measure: Changes of CMV-DNA copies number
timeFrame: 1 year
measure: Persistence of CMV-TCR-T cells
timeFrame: 1 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
Study officials:
affiliation: Chinese PLA General Hospital
name: Daihong Liu
role: PRINCIPAL_INVESTIGATOR
References: