Back to resultsCMV-TCR-T Cells for CMV Infection After Allogenic HSCT
Primary Purpose
CMV Infection After Allogenic HSCT
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
CMV-TCR-T cells
Sponsored by
About this trial
This is an interventional treatment trial for CMV Infection After Allogenic HSCT focused on measuring CMV, HSCT
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:
- Age ≥ 8 years.
- Understand and voluntarily sign informed consent and are willing to comply with laboratory tests and other research procedures.
- ≥ 3/6 HLA match with TCR-T cell recipients enrolled.
- Lymphocyte count = (0.8~4) × 10^9/L
- Have sufficient venous circulation, without any symptoms that do not allow blood cell isolation.
Exclusion Criteria:
- Patients with active aGVHD one day before TCR-T cell infusion.
- 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.
- Anticipated to take immunosuppressive hormones on the day of TCR-T cell infusion.
- Have other malignancies.
- Have relapsed and uncontrolled hematologic malignancies.
- Serologically positive for HIV-Ab or TAP-ab.
- Positive for EBV DNA.
- Anticipated to have other cell therapies in 4 week post TCR-T cell infusion.
- Pregnant or lactating women。
- Participated in any other clinical study of drugs and medical devices before 30 days of enrollment.
- 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.
- 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.
Sites / Locations
- Chinese PLA General HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CMV-TCR-T cells
Arm 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.
Outcomes
Primary Outcome Measures
Adverse events
Percentage of participants with adverse events.
Secondary Outcome Measures
Changes of CMV-DNA copies number
Quantitative PCR will be used to determine viral copy numbers in peripheral blood.
Persistence of CMV-TCR-T cells
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.
Full Information
NCT ID
NCT05140187
First Posted
November 18, 2021
Last Updated
March 25, 2023
Sponsor
Chinese PLA General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05140187
Brief Title
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
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 15, 2021 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese PLA General Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CMV Infection After Allogenic HSCT
Keywords
CMV, HSCT
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CMV-TCR-T cells
Arm Type
Experimental
Arm 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.
Intervention Type
Biological
Intervention Name(s)
CMV-TCR-T cells
Intervention Description
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.
Primary Outcome Measure Information:
Title
Adverse events
Description
Percentage of participants with adverse events.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Changes of CMV-DNA copies number
Description
Quantitative PCR will be used to determine viral copy numbers in peripheral blood.
Time Frame
1 year
Title
Persistence of CMV-TCR-T cells
Description
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.
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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:
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:
Patients with active aGVHD one day before TCR-T cell infusion.
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.
Anticipated to take immunosuppressive hormones on the day of TCR-T cell infusion.
Have other malignancies.
Have relapsed and uncontrolled hematologic malignancies.
Serologically positive for HIV-Ab or TAP-ab.
Pregnant or lactating women.
Anticipated to have other cell therapies in 4 week post TCR-T cell infusion.
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:
Positive for any of the following: HbsAg, HBeAg, HBV-DNA, HCV-Ab, HCV-RNA, HIV-Ab, TP-Ab, EBV-DNA or CMV-DNA;
Other uncontrolled infection;
Have taken immunosuppressive drugs 1 week before PBMC collection;
Any condition that would, in the investigator's judgment, make it unsuitable for the donors to be enrolled.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Daihong Liu
Phone
86-13681171597
Email
daihongrm@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Liping Dou
Phone
86-13681207138
Email
lipingruirui@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daihong Liu
Organizational Affiliation
Chinese PLA General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Chinese PLA General Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100853
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daihong Liu, doctor
Phone
86-13681171597
Email
daihongrm@163.com
First Name & Middle Initial & Last Name & Degree
Liping Dou, doctor
Phone
+8613681207138
Email
lipingruirui@163.com
12. IPD Sharing Statement
Learn more about this trial
CMV-TCR-T Cells for CMV Infection After Allogenic HSCT
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