Preemptive Therapy With CMV-specific T Cells Infusion to Prevent Refractory CMV Infection Post Transplantation

NCT02985775 | Completed Phase 1 DMC

• 1 other identifier: 2016PHB153
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

Cytomegalovirus (CMV) infections remain an important cause of morbidity and mortality in allogeneic hematopoietic cell transplant (HSCT) recipients, especially in patients received haploidentical transplantation. During the past decades, prophylactic or preemptive treatment with antiviral drugs has significantly reduce the incidence of early-onset CMV infection. Unfortunately, prolonged antiviral treatment is associated with substantial toxicity and may delay recovery of virus specific immune responses, resulting in an increasing of late-onset CMV disease. To date, adoptive immunotherapies have been developed as treatment alternatives to antiviral agents for CMV infection after HSCT. Studies have demonstrated that prophylactic or preemptive therapy with donor CMV-specific T cells can restore antiviral immunity and clear CMV viremia after transplantation. In this prospective clinical phase I/II trial, we propose to reconstitute antiviral immunity against CMV by preemptive transfer of CMV-specific T cells at an early time point after allogeneic stem cell transplantation. We also propose to demonstrate whether protect against CMV is associated with recovery of CMV-specific T cells.

Conditions

CMV Infection

Keywords

CMV-specific T cell; haploidentical stem cell transplantation; immunologic response; acute GVHD

Outcome Measures

Primary Outcomes (2)

• Virologic efficacy of CMVpp65-specific T cells for prophylaxis against refractory CMV infection after haploidentical stem cell transplantation

  Virologic efficacy defined as reduction of refractory CMV infection during 6 months after transplantation

  6 months

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 after adoptive transfer of CMV-specific T-cells

  Patients were closely monitored for acute infusion-related toxicities during the first 2 to 4 hours following T-cell transfer and later on for acute and chronic GVHD during the whole observation period.

  6 months

Secondary Outcomes (5)

• Using Flow cytometry to evaluate the CMV-specific T cells reconstitution before and after CMV-CTL adoptive infusion post transplantation

  6 months

• Reduction complications associated with CMV infection

  6 months

• Reduction relapse rate of the primary disease

  6 months

• Increase overall survival

  6 months

• Increase disease-free survival

  6 months

Study Arms (1)

Donor-derived CMVpp65-specific T cells

EXPERIMENTAL

Intervention to be adminstered is about 1 million per kg CMVpp65-specific T cells infusion once acute GVHD ocurred post haploidentical transplantation.

Biological: Donor-derived CMVpp65-specific T cells

Interventions

Donor-derived CMVpp65-specific T cells BIOLOGICAL

About 1 million per kg CMVpp65-specific T cells will be infused once acute GVHD ocurred post haploidentical transplantation.

Donor-derived CMVpp65-specific T cells

Eligibility Criteria

• Age: 15 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Primary disease is leukemia or MDS.
• Patients receive haploidentical stem cell transplantation.
• Both patients and donors are CMV seropositive (IgG positive).
• Subjects must be capable of, and willing to provide written informed consent to participate in the study. Subjects unable to provide written informed consent by themselves may be consented through their legal representative.

You may not qualify if:

• Participation in another industry-sponsored clinical study where treatment for CMV is already specified by the study protocol.
• Patients received other adoptive immunotherapy such as donor lymphocyte infusion (DLI), Epstein-Barr virus (EBV)-specific T cells and so on.

Sponsors & Collaborators

• Peking University People's Hospital: lead

Study Sites (1)

Peking University People's Hospital & Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation

Beijing, Beijing Municipality, 100044, China

Location

Related Publications (1)

• Zhao XY, Pei XY, Chang YJ, Yu XX, Xu LP, Wang Y, Zhang XH, Liu KY, Huang XJ. First-line Therapy With Donor-derived Human Cytomegalovirus (HCMV)-specific T Cells Reduces Persistent HCMV Infection by Promoting Antiviral Immunity After Allogenic Stem Cell Transplantation. Clin Infect Dis. 2020 Mar 17;70(7):1429-1437. doi: 10.1093/cid/ciz368.

  PMID: 31067570 DERIVED

MeSH Terms

Conditions

Cytomegalovirus Infections

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Study Officials

• Xiao-jun Huang, MD,PHD

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD,PHD, Study Principal Investigator

Study Record Dates

• First Submitted: November 28, 2016
• First Posted: December 7, 2016
• Study Start: January 1, 2017
• Primary Completion: March 1, 2018
• Study Completion: March 1, 2019
• Last Updated: March 10, 2020

Record last verified: 2020-03

Locations

CN (1)