Clinical Trial: Preemptive Adoptive CMV-CTL Infusion to Prevent Refractory CMV Infection Post Haplo-HSCT

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Evaluate the Safety and Efficacy of Preemptive Adoptive CMV-pp65 Specific T Cells Infusion for Prevention of Refractory CMV Infection in Patients After Haploidentical Stem

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 CMVpp65-specific T cells (CMV-CTLs) 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-CTLs.


Detailed Summary: 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.
Sponsor: Peking University People's Hospital

Current Primary Outcome:

  • 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

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


Original Secondary Outcome: Same as current

Information By: Peking University People's Hospital

Dates:
Date Received: November 28, 2016
Date Started: November 2016
Date Completion: December 2017
Last Updated: December 6, 2016
Last Verified: December 2016