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

Sponsor

Peking University People's Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT02985775

Collaborator

(none)

Enrollment

Location

Arm

25.9

Actual Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
CMV Infection	Biological: Donor-derived CMVpp65-specific T cells	Phase 1/Phase 2

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

Actual Enrollment :

41 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

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

Actual Study Start Date :

Jan 1, 2017

Actual Primary Completion Date :

Mar 1, 2018

Actual Study Completion Date :

Mar 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: 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.

Arm

Intervention/Treatment

Experimental: 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.

Biological: 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.

Outcome Measures

Primary Outcome Measures

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

Using Flow cytometry to evaluate the CMV-specific T cells reconstitution before and after CMV-CTL adoptive infusion post transplantation [6 months]
Immunologic efficacy defined as in vivo reconstitution of CMV-specific antiviral immunity after adoptive transfer of CMV-CTLs
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peking University People's Hospital & Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation	Beijing	Beijing	China	100044