Clinical trial NCT02985775: Preemptive Therapy With CMV-specific T Cells Infusion to Prevent Refractory CMV Infection Post Transplantation
Official title: Evaluate the Safety and Efficacy of Preemptive Adoptive CMV-specific T Cells Infusion for Prevention of Refractory CMV Infection in Patients After Haploidentical Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: CMV Infection
Keywords: CMV-specific T cell
haploidentical stem cell transplantation
immunologic response
acute GVHD
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2016-12-07
Enrollment: 41
Sex: ALL
Minimum age (years): 15
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Virologic efficacy of CMVpp65-specific T cells for prophylaxis against refractory CMV infection after haploidentical stem cell transplantation
timeFrame: 6 months
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 after adoptive transfer of CMV-specific T-cells
timeFrame: 6 months
Secondary outcomes:
measure: Using Flow cytometry to evaluate the CMV-specific T cells reconstitution before and after CMV-CTL adoptive infusion post transplantation
timeFrame: 6 months
measure: Reduction complications associated with CMV infection
timeFrame: 6 months
measure: Reduction relapse rate of the primary disease
timeFrame: 6 months
measure: Increase overall survival
timeFrame: 6 months
measure: Increase disease-free survival
timeFrame: 6 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital & Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation
state: Beijing
Study officials:
affiliation: Peking University People's Hospital
name: Xiao-jun Huang, MD,PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.