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

Peking University

Status and phase: Completed; Phase 2; Phase 1

Conditions: CMV Infection

Treatments: Biological: Donor-derived CMVpp65-specific T cells

Study type: Interventional

Funder types: Other

Identifiers

NCT02985775

2016PHB153

Details and patient eligibility

About

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.

Full 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.

Enrollment: 41 patients

Sex: All

Ages: 15 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

41 participants in 1 patient group

Donor-derived CMVpp65-specific T cells

Experimental group

Description:

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

Treatment:

Biological: Donor-derived CMVpp65-specific T cells