Back to resultsCMV-TCR-T Cells for Refractory CMV Infection After HSCT
Primary Purpose
Allogeneic Hematopoietic Stem Cell Transplantation, CMV Infection
Status
Unknown status
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 Allogeneic Hematopoietic Stem Cell Transplantation
Eligibility Criteria
Inclusion Criteria:
- Patients with acute leukemia (AL) or myelodysplastic syndrome (MDS) who receive haploid allogeneic hematopoietic stem cell transplantation, pre-transplantation assessment ≤CR2;
- Age 18-60, including boundary value, gender unlimited;
- Refractory CMV infection occurred in the early stage of transplantation : After 2 weeks of standard antiviral treatment, the CMV DNA copy number continued to be ≥1000 copies/mL, and the CMV DNA copy number at the beginning of the treatment decreased by <log10 ；
- The transplant donor's HLA-A matching is one of 2402, 0201 or 1101, and the physical examination is qualified;
- ECOG ≤ 3, estimated life expectancy> 3 months;
- 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;
- Have received cell therapy such as DLI, CTL, CAR-T, NK or participated in any other clinical research on drugs and medical devices;
- Patients who have developed CMV disease;
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;
- Pregnant or lactating women;
- The researchers found that it was unsuitable for the recipients to be enrolled.
Sites / Locations
- Peking University Institute of Hematology,People's hospital Peking UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CMV-TCR-T cells
Arm Description
Patients who enrolled will receive one dose of CMV-TCR-T cells. The dosage ranges from 0.3×10^6 to 1×10^7 TCR+T/Kg.
Outcomes
Primary Outcome Measures
Adverse events
Percentage of participants with adverse events
Secondary Outcome Measures
Changes of CMV-DNA copies
Changes of CMV-DNA copies
CMV-specific immunity reconstitution
In vivo persistence of the infused CMV-TCR-T cells and reconstitution of CMV-specific immunity
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05089838
Brief Title
CMV-TCR-T Cells for Refractory CMV Infection After HSCT
Official Title
A Study of CMV-TCR-T Cells in the Treatment of Refractory CMV Viremia After HSCT
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Unknown status
Study Start Date
January 6, 2021 (Actual)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
October 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Xiao-Jun Huang
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a single centre, single arm, open-label, phase I study to evaluate the safety and effectiveness of CMV-TCR-T cell immunotherapy in treating refractory CMV infection after HSCT.
Detailed Description
CMV infection is a major and potentially life-threatening complication after allogenic hematopoietic stem cell transplantation (allo-SCT). Pharmacotherapy with ganciclovir and foscarnet remains the mainstay of treatment and has significantly improve clinical results, however, it is unsatisfactory owing to toxicity, limited efficacy and risk of developing resistance.
In recent years, adoptive T cell therapy has been proposed as an alternative option for CMV infection after allo-SCT. However, patients with transplants from CMV-negative donors are at highest risk, and an adoptive therapy is missing because CMV-specific T cells are not available.
CMV TCR-transduced donor-derived T Cells (CMV-TCR-T cells) is an attractive strategy to specifically redirect T-cell immunity toward CMV. In this prospective clinical phase I trial, we propose to evaluate the safety and efficacy of stem cell donor-derived CMV-TCR-T cells for patients with refractory CMV infection after allo-SCT. Donor derived CMV-TCR-T(HLA-A*1101\0201\2402) cells will be intravenously infused with a escalated dose of 0.3-1×10E7CMV-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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Allogeneic Hematopoietic Stem Cell Transplantation, CMV Infection
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
Patients who enrolled will receive one dose of CMV-TCR-T cells. The dosage ranges from 0.3×10^6 to 1×10^7 TCR+T/Kg.
Intervention Type
Biological
Intervention Name(s)
CMV-TCR-T cells
Intervention Description
Patients who developed refractory CMV infection after allo-HSCT will be enrolled, and donor derived CMV-TCR-T(HLA-A*1101\0201\2402) cells will be intravenously infused with a escalated dose of 0.3-1×10E7CMV-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).
Primary Outcome Measure Information:
Title
Adverse events
Description
Percentage of participants with adverse events
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Changes of CMV-DNA copies
Description
Changes of CMV-DNA copies
Time Frame
3 months
Title
CMV-specific immunity reconstitution
Description
In vivo persistence of the infused CMV-TCR-T cells and reconstitution of CMV-specific immunity
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with acute leukemia (AL) or myelodysplastic syndrome (MDS) who receive haploid allogeneic hematopoietic stem cell transplantation, pre-transplantation assessment ≤CR2;
Age 18-60, including boundary value, gender unlimited;
Refractory CMV infection occurred in the early stage of transplantation : After 2 weeks of standard antiviral treatment, the CMV DNA copy number continued to be ≥1000 copies/mL, and the CMV DNA copy number at the beginning of the treatment decreased by <log10 ；
The transplant donor's HLA-A matching is one of 2402, 0201 or 1101, and the physical examination is qualified;
ECOG ≤ 3, estimated life expectancy> 3 months;
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;
Have received cell therapy such as DLI, CTL, CAR-T, NK or participated in any other clinical research on drugs and medical devices;
Patients who have developed CMV disease;
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;
Pregnant or lactating women;
The researchers found that it was unsuitable for the recipients to be enrolled.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lanping Xu, PhD,MD
Phone
86-010-88324671
Email
lpxu_0415@sina.com
First Name & Middle Initial & Last Name or Official Title & Degree
Xuying Pei, PhD
Phone
86-010-88324671
Email
peixuying08@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lanping Xu, PhD,MD
Organizational Affiliation
Peking University People's Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Peking University Institute of Hematology,People's hospital Peking University
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100044
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lanping Xu, Prof.
Phone
8613641028627
Email
lpxu_0415@sina.com
First Name & Middle Initial & Last Name & Degree
Yanru Ma
Phone
8613641134402
Email
lpxu_0415@vip.sina.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
CMV-TCR-T Cells for Refractory CMV Infection After HSCT
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