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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02985775
Recruitment Status : Recruiting
First Posted : December 7, 2016
Last Update Posted : April 24, 2018
Information provided by (Responsible Party):
Xiaojun Huang, Peking University People's Hospital

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 41 participants
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
Study Start Date : November 2016
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : June 2018

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.

Primary Outcome Measures :
  1. 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

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

  2. Reduction complications associated with CMV infection [ Time Frame: 6 months ]
  3. Reduction relapse rate of the primary disease [ Time Frame: 6 months ]
  4. Increase overall survival [ Time Frame: 6 months ]
  5. Increase disease-free survival [ Time Frame: 6 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02985775

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Contact: Xiao-jun Huang, MD,PHD +861088324516

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China, Beijing
Peking University People's Hospital & Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation Recruiting
Beijing, Beijing, China, 100044
Contact: Xiang-yu Zhao, PHD    1088324671      
Sponsors and Collaborators
Peking University People's Hospital
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Principal Investigator: Xiao-jun Huang, MD,PHD Peking University People's Hospital

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Responsible Party: Xiaojun Huang, MD,PHD, Study Principal Investigator, Peking University People's Hospital Identifier: NCT02985775     History of Changes
Other Study ID Numbers: 2016PHB153
First Posted: December 7, 2016    Key Record Dates
Last Update Posted: April 24, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Xiaojun Huang, Peking University People's Hospital:
CMV-specific T cell
haploidentical stem cell transplantation
immunologic response
acute GVHD

Additional relevant MeSH terms:
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Communicable Diseases
Cytomegalovirus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases