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

NCT ID: NCT03159364

Last Updated: 2019-09-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-07-15

Study Completion Date

2021-12-31

Brief Summary

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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.

Detailed Description

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Background:

Opportunistic infections are major causes of transplant-related morbidity and mortality in immunosuppressed patients, especially in the early post-transplant period. CMV, EBV, adenovirus (AdV), BK virus (BKV) and other viruses or non-viral pathogens may lead to life-threatening infections after transplantation.

Adoptive immunotherapy with cytotoxic T lymphocytes (CTLs) reactive with specific microbial antigens has proven to be effective without stimulating acute graft-versus-host disease (GVHD) owing to the significantly reduced nonspecific alloreactivity. This study aims to evaluate the safety and efficacy of treating opportunistic infections with microbial-specific CTLs in immune compromised patients.

Objective:

Primary study objectives: Infusion of autologous or allogenic pathogen-specific CTL to patients by I.V., to evaluate the safety.

Secondary study objectives: To evaluate the anti-microbial efficacy of IV-infused autologous or allogenic pathogen-specific CTLs.

Design:

Peripheral blood mononuclear cells (PBMC) will be obtained through apheresis. T cells from PBMC will be activated and enriched by dendritic cells with pathogen specific antigens. Cell preparation time is approximately 12-17 days. Subject will receive infusions of 1x105\~1x106 cells/kg body weight of CTLs via IV infusion. Patients are followed weekly for one month after the infusion, monthly for 3 months, and then every 3 months until the trial ends.

Conditions

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Infusion of pathogen-specific CTLs

Repetitive CTL infusions to treat microbial infections

Group Type EXPERIMENTAL

pathogen-specific CTLs

Intervention Type BIOLOGICAL

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

Interventions

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pathogen-specific CTLs

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

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

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.
* Human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) or tuberculosis (TB) test is negative.
* Physical examination in line with the standard of healthy blood donors.

Exclusion Criteria

* 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.
Minimum Eligible Age

6 Months

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Shenzhen Geno-Immune Medical Institute

OTHER

Sponsor Role lead

Responsible Party

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Lung-Ji Chang

President

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Lung-Ji Chang, PhD

Role: PRINCIPAL_INVESTIGATOR

Shenzhen Geno-Immune Medical Institute

Locations

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Shenzhen Geno-immune Medical Institute

Shenzhen, Guangdong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Lung-Ji Chang, PhD

Role: CONTACT

+86(755)8672 5195

Facility Contacts

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Lung-Ji Chang, PhD

Role: primary

86-755-86725195

Other Identifiers

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GIMI-IRB-17009

Identifier Type: -

Identifier Source: org_study_id

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