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

A Study of CMV-TCR-T Cells in the Treatment of Refractory CMV Viremia After HSCT

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.

Study Overview

• Status: Recruiting
• Conditions: Allogeneic Hematopoietic Stem Cell Transplantation; CMV Infection
• Intervention / Treatment: Biological: CMV-TCR-T cells

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).

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

Contacts and Locations

• Study Contact: Name: Lanping Xu, PhD,MD; Phone Number: 86-010-88324671; Email: lpxu_0415@sina.com
• Study Contact Backup: Name: Xuying Pei, PhD; Phone Number: 86-010-88324671; Email: peixuying08@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University Institute of Hematology,People's hospital Peking University
      • Contact: Lanping Xu, Prof.; Phone Number: 8613641028627; Email: lpxu_0415@sina.com
      • Contact: Yanru Ma; Phone Number: 8613641134402; Email: lpxu_0415@vip.sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with acute leukemia (AL) or myelodysplastic syndrome (MDS) who receive haploid allogeneic hematopoietic stem cell transplantation, pre-transplantation assessment ≤CR2;
2. Age 18-60, including boundary value, gender unlimited;
3. 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 ；
4. The transplant donor's HLA-A matching is one of 2402, 0201 or 1101, and the physical examination is qualified;
5. ECOG ≤ 3, estimated life expectancy> 3 months;
6. Patients who voluntarily sign informed consent and are willing to comply with treatment plans, visit arrangements, laboratory tests and other research procedures.

Exclusion Criteria:

1. Patients with active aGVHD III-IV and / or mild and severe cGVHD;
2. Have received cell therapy such as DLI, CTL, CAR-T, NK or participated in any other clinical research on drugs and medical devices;
3. Patients who have developed CMV disease;

4. 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;
5. Pregnant or lactating women;
6. The researchers found that it was unsuitable for the recipients 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; 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.	Biological: CMV-TCR-T cells; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Percentage of participants with adverse events	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of CMV-DNA copies	Changes of CMV-DNA copies	3 months
CMV-specific immunity reconstitution	In vivo persistence of the infused CMV-TCR-T cells and reconstitution of CMV-specific immunity	3 months

Collaborators and Investigators

• Sponsor: Xiao-Jun Huang
• Investigators: Study Chair: Lanping Xu, PhD,MD, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2021
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: October 11, 2021
• First Submitted That Met QC Criteria: October 11, 2021
• First Posted (Actual): October 22, 2021

Study Record Updates

• Last Update Posted (Actual): October 22, 2021
• Last Update Submitted That Met QC Criteria: October 11, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; DNA Virus Infections; Herpesviridae Infections; Infections; Cytomegalovirus Infections
• Other Study ID Numbers: 2020PHD014-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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