CMV Infection and Immune Intervention After Transplantation

CMV Infection and Immune Intervention After Haploidentical Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective or even the only way to cure blood malignant diseases. Cytomegalovirus (CMV) infection is a serious early complication of allo-HSCT. Its high incidence and poor prognosis can cause a series of terminal organ diseases such as CMV pneumonia, encephalitis, and enteritis,which seriously affecting the prognosis of patients post allo-HSCT.

Our data show that rapid reconstruction of NK cells after transplantation can reduce the incidence of CMV infection. Patients with a rapid reconstruction of NKG2C after transplantation have a low CMV infection rate, and patients with strong secretion of IFN-gamma of NK after transplantation have low CMV infection.

Our previous research showed that trophoblast cells transfected with IL-21 and 4-1BBL can achieve a large number of clinical-grade expansion of NK cells (mIL-21 / 4-1BBL NK cells), and mIL-21 / 4-1BBL NK cells It is safe to treat patients with minimal residual disease (MRD) positive AML after transplantation, and can induce MRD to turn negative. Previous studies have shown that adoptive infusion of expanded NK cells after haplotype transplantation is safe and can improve the functional reconstruction of NK cells. Therefore, we hypothesized that the infusion of NK cells can improve the antiviral capacity of NK cells, thereby effectively reducing the CMV infection. Incidence.

Study Overview

• Status: Recruiting
• Conditions: Transplantation Infection; CMV Viremia
• Intervention / Treatment: Biological: expanded NK cells

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiang-Yu Zhao; Phone Number: 861088325949; Email: zhao_xy@bjmu.edu.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Peking University Institute of Hematology
      • Contact: Xiang-Yu Zhao, M.D., PhD; Phone Number: +861088325949; Email: zhao_xy@bjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with acute leukemia (AL) or myelodysplastic syndrome (MDS) or myeloma or lymphoma undergoing haploidentical allogeneic stem cell transplantation
2. No CMV infection by 20 days ± 3 days after transplantation
3. No active acute GVHD by 20 days ± 3 days after transplantation
4. The dose of prednisolone was less than 0.5mg / kg / d within 72 hours before and after infusion of NK cells
5. Prior to transplantation, the CMV IgG of the recipient and donor were positive, and the recipient had a suitable donor to expand NK cells.
6. Patient age 16-65 years
7. Donor age 16-65 years
8. Patient Karnofsky score> 70%
9. Estimated survival> 3 weeks
10. Patient agrees to participate in study

Exclusion Criteria:

1. Participants in any other clinical trials within 1 month before enrollment
2. Active infection
3. HBV or HCV or HIV carriers
4. With moderate to severe renal dysfunction (blood creatinine> 130umol / L) and / or liver dysfunction (total bilirubin> 34umol / L, ALT, AST> 2 times the upper limit of normal) before NK infusion
5. Researchers do not consider it appropriate to participate in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• 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: adaptive NK cells infusion post transplantation; Adaptive donors expanded NK cells infusion at day 20±3d and 27±3d post transplantation	Biological: expanded NK cells; Donor derived expanded NK cells were infused to patients at around days 20±3d, and 27±3d post transplantation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of CMV infection post transplantation	Whether to reduce the incidence of CMV infection in patients post haploidentical transplantation	within 180 days post transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of refractory CMV infection post transplantation	Whether to reduce the incidence of refractory CMV infection in patients post haploidentical transplantation	within 180 days post transplantation
Cumulative incidence of CMV disease post transplantation	Whether to reduce the incidence of CMV disease in patients post haploidentical transplantation	within 180 days post transplantation
Enhanced anti-CMV function of reconstituted NK cells	Whether to enhance the anti-CMV function of reconstituted NK cells	within 180 days post transplantation
cumulative incidence of TRM	Whether to reduce the incidence of transplantation related mortality in patients post haploidentical transplantation	within 180 days post transplantation
cumulative incidence of overall survival	Whether to increase the incidence of overall survival in patients post haploidentical transplantation	within 180 days post transplantation
cumulative incidence of disease free survival	Whether to increase the incidence of disease free survival in patients post haploidentical transplantation	within 180 days post transplantation

Collaborators and Investigators

• Sponsor: Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2020
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: March 23, 2020
• First Submitted That Met QC Criteria: March 23, 2020
• First Posted (Actual): March 24, 2020

Study Record Updates

• Last Update Posted (Actual): June 11, 2021
• Last Update Submitted That Met QC Criteria: June 10, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; DNA Virus Infections; Sepsis; Herpesviridae Infections; Infections; Communicable Diseases; Viremia; Cytomegalovirus Infections
• Other Study ID Numbers: 2016PhB175-01

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