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

NCT ID: NCT02985775

Last Updated: 2020-03-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-31
• Study Completion Date: 2019-03-31

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.

Detailed Description

Acute lymphoblastic leukemia (ALL) patients enrolled into this clinical trial are standard risk patients diagnosed with acute leukemia or myelodysplastic syndrome (MDS) and received haploidentical blood and marrow transplantation. When patients develop acute graft versus host disease (aGVHD), CMVpp65-specific T cells will be generated and transferred to the aGVHD controlled patients(patients who do not develop aGVHD are at low risk of refractory CMV infection, and are not include in treated group). Physical exams and blood tests will be performed -2w, -0d before and +1d, +2w, +4w, +8w, +12w, +24w after adoptive CMV-CTL transfusion. The end points were safety and clinical and immunologic response. Following time is 12 months.

Conditions

CMV Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Donor-derived CMVpp65-specific T cells

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

Group Type: EXPERIMENTAL

Donor-derived CMVpp65-specific T cells

Intervention Type: BIOLOGICAL

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

Interventions

Donor-derived CMVpp65-specific T cells

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Primary disease is leukemia or MDS.

2. Patients receive haploidentical stem cell transplantation.

3. Both patients and donors are CMV seropositive (IgG positive).

4. 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.

Exclusion Criteria

1. Participation in another industry-sponsored clinical study where treatment for CMV is already specified by the study protocol.

2. Patients received other adoptive immunotherapy such as donor lymphocyte infusion (DLI), Epstein-Barr virus (EBV)-specific T cells and so on.

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Xiaojun Huang,MD

MD,PHD, Study Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xiao-jun Huang, MD,PHD

Role: PRINCIPAL_INVESTIGATOR

Peking University People's Hospital

Locations

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

Beijing, Beijing Municipality, China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 31067570 (View on PubMed)

Other Identifiers

2016PHB153

Identifier Type: -

Identifier Source: org_study_id