CMV-TCR-T Cells for CM Virus Infection After HSCT

A Pilot Study of CMV-TCR-T Cells in CM Virus Infection Diseases After HSCT

This is a single cente, single arm, open-label, phase I study to evaluate the safety and effectiveness of CMV-TCR-T cell immunotherapy in treating CMV virus infection after HSCT.

Study Overview

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

Detailed Description

CMV infection is a common virus infection of HSCT, and which is highly related with the failure of transplantation and survival time of transplant patients. To evaluate the safety and efficacy of allogenic CMV-TCR-T cell therapy in subjects with CMV infection, patients with CMV emias or deseases will be enrolled, and donor derived CMV-TCR-T(HLA-A*1101\0201\2402) cells will be intravenously infused with a escalated dose of 0.1-1×106 CMV-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 (Actual): 17
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xingyu Cao, Ph.D; Phone Number: +8619910757321; Email: caoxingyu@hotmail.com

Study Locations

• China
  • Hebei
    • Sanhe, Hebei, China, 065200
      • Hebei yanda Ludaopei Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 1-70 years, including boundary values, gender unlimited;
2. Allogenic hematopoietic stem cell transplantation patients with CMV infection disease or persistent CMV emia;

3. At least one of the following conditions after allogeneic HSCT:

   • After trested with 2-week standard antiviral drug, compared to the baseline of treatment, the decrease of CMV DNA copies number was less than 1log10, and the CMV DNA copies number is greater than 1000 copies/ mL ;
   • Unable to tolerate the toxic and side effects of antiviral drugs,such as bone marrow hematopoietic suppression, nephrotoxicity;
4. Estimated life expectancy ≥3 months；
5. ECOG 3;
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. Received cell therapy such as DLI,CTL,CAR-T or participated in any other clinical study of drugs and medical devices before 30 days of enrollment.
3. Pregnant or lactating women;
4. Intracranial hypertension or confusion; respiratory failure; disseminated intravascular coagulation;

5. 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;
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; The patients will receive one dose of CMV-TCR-T.The dosage ranges from 0.1×10^6 to 1×10^6 TCR+T/Kg.	Biological: CMV-TCR-T cells; Patients with CMV emias or CMV disease will be enrolled, and donor derived CMV-TCR-T(HLA-A*1101\0201\2402) cells will be intravenously infused with a escalated dose of 0.1-1×106 CMV-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
Percentage of adverse events	Percentage of participants with adverse events.	3months

Secondary Outcome Measures

Outcome Measure	Time Frame
Persistence of TCR-T cells	3months
Changes of CMV-DNA copies number	3months

Collaborators and Investigators

• Sponsor: Hebei Yanda Ludaopei Hospital
• Collaborators: China Immunotech (Beijing) Biotechnology Co., Ltd.
• Investigators: Study Director: Xingyu Cao, Ph.D, Hebei yanda Ludaopei Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2019
• Primary Completion (Actual): November 15, 2022
• Study Completion (Actual): November 15, 2022

Study Registration Dates

• First Submitted: November 4, 2019
• First Submitted That Met QC Criteria: November 4, 2019
• First Posted (Actual): November 6, 2019

Study Record Updates

• Last Update Posted (Actual): January 12, 2023
• Last Update Submitted That Met QC Criteria: January 11, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; DNA Virus Infections; Herpesviridae Infections; Infections; Communicable Diseases; Virus Diseases; Cytomegalovirus Infections
• Other Study ID Numbers: HXYT-005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No