Antigen-specific Cytotoxic T Cells in the Treatment of Opportunistic Infections

NCT03159364 | Unknown Phase 1

• 1 other identifier: GIMI-IRB-17009
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Epstein Barr Virus (EBV) or Cytomegalovirus (CMV) infection results in significant morbidity and mortality in hematopoietic stem cell transplantation (HSCT) patients. HSCT patients often face opportunistic infections due to the immunosuppressive state during transplantation. Antimicrobial drugs are usually used for prophylactic purposes and for treatment after early detectable infections. Unfortunately, some patients develop resistance to such drug treatment. In addition to HSCT patient, immune compromised patient may also be victim to opportunistic infections. Many infections can be effectively managed by functional immune recovery. In this study, the safety and efficacy of microbial-specific cytotoxic T lymphocytes (CTLs) will be investigated.

Conditions

Pathogen Infection; EBV Infection; CMV Infection; Adenovirus Infection; BKV Infection; Fungus Infection; Tuberculosis

Keywords

CTL; Virus CTL; Fungus CTL; TB CTL

Outcome Measures

Primary Outcomes (2)

• Using CTCAE 4 standard to evaluate the level of adverse events after receiving autologous or allogenic pathogen-specific CTL infusion

  to evaluate the level of adverse events with CTCAE 4

  24 weeks

• Viral load change after Virus-CTL infusion

  The viral load response to the Virus-CTL infusion will be assessed by specific PCR of peripheral blood after infusion.

  2 months

Secondary Outcomes (3)

• The incidence of CTL infusion syndrome mimicking grade Ⅱ~Ⅳ GVHD within 30 days after the last dose of CTL infusion

  1 months

• Reconstitution of anti-microbial immunity monitored by flow cytometry

  6 months

• Number of patients with chronic GVHD-like symptom

  6 months

Study Arms (1)

Infusion of pathogen-specific CTLs

EXPERIMENTAL

Repetitive CTL infusions to treat microbial infections

Biological: pathogen-specific CTLs

Interventions

pathogen-specific CTLs BIOLOGICAL

Patients will receive approximately 1x10\^5\~1x10\^6 CTLs/kg as a single infusion via IV injection and may receive additional infusions.

Infusion of pathogen-specific CTLs

Eligibility Criteria

• Age: 6 Months - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with or without hematopoietic stem cell transplantation / organ transplant recipients need to meet the following conditions:
• Evidence of CMV, EBV, ADV, BKV or known pathogen infection (viral DNA, immunohistochemical cytology positive); contraindications or invalid to anti-microbial drugs.
• Subjects with virus DNA increased in the 2 consecutive peripheral blood samples (≥ 1000 genomic copies/ml blood) at least 24 hours apart.
• Initial hematopoietic reconstitution: neutrophils (ANC) ≥ 0.5x109 / L, platelet (PLT) ≥ 20x109 / L.
• Patients with pahogen disease (organ/ tissue infiltration) symptoms, fever, diarrhea, or lymphadenopathy, regardless of the level of peripheral blood virus DNA, and confirmed by the presence of viral DNA or microbial antigens within body fluid or biopsy.
• The subject / guardian has signed a written consent form before any trial begins.
• Proper renal and hepatic functions (ULN denotes "upper limit of normal range"):
• Creatinine ≤ 2\*ULN.
• Bilirubin ≤ 2\*ULN.
• SGOT ≤ 3\*ULN.
• SGPT≤ 3\*ULN.
• If CTL is not from the patient's own, then the provider of CTLs needs to meet the following criteria:
• Did not receive chemotherapy or radiotherapy within 4 weeks prior to blood collection, and did not take any steroids for the previous week, did not use Penicillin or β-lactam antibiotics, or the lowest dose of other antibiotics.
• White blood cells ≥ 3,500 / μl, lymphocytes ≥ 750 / μl.
• Obtain a signed informed consent from the patient and / or the guardian or the donor of the BMT recipient.

You may not qualify if:

• Subject infected with HCV (HCV antibody positive), HBV (HBsAg positive), HIV (HIV antibody positive), or HTLV (HTLV antibody positive).
• GVHD (graft-versus-host disease) performance score at II-IV.
• Subject is albumin-intolerant.
• Subject with life expectancy less than 4 weeks.
• Subject participated in other investigational somatic cell therapies within past 30 days.
• Subject with positive pregnancy test result.

Sponsors & Collaborators

• Shenzhen Geno-Immune Medical Institute: lead

Study Sites (1)

Shenzhen Geno-immune Medical Institute

Shenzhen, Guangdong, 518000, China

RECRUITING

MeSH Terms

Conditions

Epstein-Barr Virus Infections; Cytomegalovirus Infections; Adenoviridae Infections; Mycoses; Tuberculosis

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Bacterial Infections and Mycoses; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections

Study Officials

• Lung-Ji Chang, PhD

  Shenzhen Geno-Immune Medical Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lung-Ji Chang, PhD

CONTACT

+86(755)8672 5195; c@szgimi.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: President

Study Record Dates

• First Submitted: May 16, 2017
• First Posted: May 18, 2017
• Study Start: July 15, 2017
• Primary Completion: July 31, 2020
• Study Completion: December 31, 2021
• Last Updated: September 19, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)