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

Adoptive Immunotherapy With Donor-derived CMV-TCR-T Cells for Patients With CMV Infection After Allogenic HSCT

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.

Study Overview

• Status: Recruiting
• Conditions: CMV Infection After Allogenic HSCT
• Intervention / Treatment: Biological: CMV-TCR-T cells

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.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Daihong Liu; Phone Number: 86-13681171597; Email: daihongrm@163.com
• Study Contact Backup: Name: Liping Dou; Phone Number: 86-13681207138; Email: lipingruirui@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100853
      • Recruiting
      • Chinese PLA General Hospital
      • Contact: Daihong Liu, Doctor; Phone Number: 86-13681171597; Email: daihongrm@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CMV-TCR-T cells; 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.	Biological: CMV-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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Percentage of participants with adverse events.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of CMV-DNA copies number	Quantitative PCR will be used to determine viral copy numbers in peripheral blood.	1 year
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.	1 year

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital
• Investigators: Principal Investigator: Daihong Liu, Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2021
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: November 18, 2021
• First Submitted That Met QC Criteria: November 18, 2021
• First Posted (Actual): December 1, 2021

Study Record Updates

• Last Update Posted (Actual): March 29, 2023
• Last Update Submitted That Met QC Criteria: March 25, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: CMV; HSCT
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Disease Attributes; DNA Virus Infections; Herpesviridae Infections; Infections; Communicable Diseases; Cytomegalovirus Infections
• Other Study ID Numbers: S2021-344-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No