Administration of Virus Specific CTLs for the Prophylaxis and Treatment of EBV/CMV Infections After HSCT in China

Viral Infection Clinical Trial

Official title:

Adoptive Transfer of Peptide Stimulated CMV/EBV Specific Cytotoxic T Lymphocytes to Prevent and Treat EBV/CMV Infections in Patients Post Allogeneic Stem Cell Transplantation in China

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02456610
• Other study ID #: 307-CMV/EBV-CTL
• Status: Recruiting
• Phase: Phase 1
• First received: May 21, 2015
• Last updated: February 18, 2016
• Start date: May 2015
• Est. completion date: August 2016

Study information

• Verified date: February 2016
• Source: Affiliated Hospital to Academy of Military Medical Sciences
• Contact: Zhang Bin, M.D., Ph.D.
• Phone: +86-010-6694-7125
• Email: zb307ctc[@]163.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) cause significant morbidity and mortality in hematopoietic stem cell transplantation (HSCT) patients in China. Antiviral drugs given either prophylactically or as early therapy for patients with detectable viral loads appear to be an effective strategy for reducing viral infections. However, long-term treatment with these drugs is associated with significant toxicity, expense and the appearance of drug resistant virus isolates ultimately resulting in treatment failure. CMV and EBV specific T cells infusion to immunocompromised patients following HSCT is able to induce a successful anti-viral response. The primary purpose of this study is to determine the safety and efficacy of the infusion of CMV and EBV specific cytotoxic T cells (CTLs) for patients with CMV and EBV reactivation or infection.

Description:

To generate CMV/EBV specific CTLs, G-CSF mobilized hemopoietic progenitor cell (G-HPC) products or nonmobilized peripheral blood apheresis collectings were stimulated with CMV/EBV specific peptides covering most HLA alleles among Chinese populations. Once the investigators made sufficient numbers of T cells, they tested their ex vivo properties.Then a fraction of CTLs were separated for immediate infusion and the others were frozen for further infusion.

If the donor was available, the donor derived CTLs were started to produce when CMV reactivation was detected by qPCR in recipients peripheral blood. Otherwise, autologous CTLs were used. For patients at high risk of developing CMV/EBV infections after stem cell transplantation, a small part of G-HPC products was extracted for CTLs generation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: August 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patients with any type of allogeneic HSCT

• CMV, adenovirus or EBV activation or infection which is defined as below. EBV/CMV reactivation is defined as CMV/EBV DNA levels > 1000 IU/ml for a single test or > 500 IU/ml for two consecutive tests. EBV/CMV related disease were defined as the demonstration of CMV/EBV biopsy specimen or clinical diagnosis through symptoms, signs or radiography.

• Written informed consent and/or signed assent line from patient, parent or guardian

• Positive CMV or EBV serology of the donor

• Absence of severe renal disease (Creatinine > 3x upper limit normal)

• Absence of severe hepatic disease (Bilirubin > 3x upper limit normal, AST > 3x upper limit normal)

• Life expectancy > 30 days

Exclusion Criteria:

• Active acute GVHD grades II-IV

• Received donor lymphocytes infusion(DLI) within 30 days

• Received ATG or other immunosuppressive monoclonal antibodies within 30 days

• Uncontrolled acute infections

• Active and relapse of malignancy

• Received steroids treatment more than 0.5 mg/kg/day prednisone

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cytomegalovirus Infections
• Infection
• Viral Infection
• Virus Diseases

Intervention

Biological:
• CMV/EBV specific CTLs
Patients will receive approximately 1x10e6 CTLs/kg as a single infusion via IV injection and may receive 1 to 8 additional infusions at intervals of one week.

Locations

Country	Name	City	State
China	Affiliated Hospital to Academy of Military Medical Sciences	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Affiliated Hospital to Academy of Military Medical Sciences

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity of adoptive transfer of CMV/EBV specific CTLs(The increase of temperature by 1? and/or the appearance of rash within 24h after infusion)	Assessment of acute transfusion toxicity within 24 hours after adoptive CTLs transfer	24 hours	Yes
Primary	Assessment of viral load response to the CTL infusion assessed by CMV/EBV specific PCR of peripheral blood	Assess the effect of the CTL infusion on viral load	3 months	No
Secondary	The incidence of ?~?°aGVHD within 30 days after the last dose of CTL infusion		3 months	Yes
Secondary	Reconstitution of antiviral immunity monitored by flow cytometry		6 months	No
Secondary	Number of patients with chronic GVHD		6 months	Yes