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
Overview
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 41
- Locations
- 1
- Primary Endpoint
- Virologic efficacy of CMVpp65-specific T cells for prophylaxis against refractory CMV infection after haploidentical stem cell transplantation
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 15 Years to 65 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Outcomes
Primary Outcomes
Virologic efficacy of CMVpp65-specific T cells for prophylaxis against refractory CMV infection after haploidentical stem cell transplantation
Time Frame: 6 months
Virologic efficacy defined as reduction of refractory CMV infection during 6 months after transplantation
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 after adoptive transfer of CMV-specific T-cells
Time Frame: 6 months
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.
Secondary Outcomes
- Reduction relapse rate of the primary disease(6 months)
- Increase overall survival(6 months)
- Using Flow cytometry to evaluate the CMV-specific T cells reconstitution before and after CMV-CTL adoptive infusion post transplantation(6 months)
- Increase disease-free survival(6 months)
- Reduction complications associated with CMV infection(6 months)
Investigators
Xiaojun Huang,MD
MD,PHD, Study Principal Investigator
Peking University People's Hospital