Clinical trial NCT03351855: HPV Specific Immune Lymphocytes (HPV-CTLs) in the Treatment of HPV
Official title: Phase I/II and Multicenter Trial of HPV Specific Immune Lymphocytes (HPV-CTLs) in the Treatment of Human Papilloma Virus (HPV) Infection
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Human Papilloma Virus
Keywords: Human papilloma virus
Cytotoxic lymphocyte
HPV-CTL
Lead sponsor: Shenzhen Geno-Immune Medical Institute
Sponsor class: OTHER
First posted: 2017-11-24
Enrollment: 100
Sex: ALL
Minimum age (years): 6
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this clinical trial is to evaluate the safety and efficacy of IV-infused autologous or allogenic HPV-CTLs.

Detailed description: Human papilloma viruses (HPV) have been consistently implicated in causing cervical cancer especially those high-risk types (HPV 16, 18, 31, 45). Around 50-80% of women are infected by HPV within their whole lives. The current treatment of HPV-positive mainly includes drug, cryotherapy, laser, microwave, surgery and so on. Some treatments are convenient, but easy to cause pain or infection and there is still a greater risk of recurrence after treatment.

Adoptive immunotherapy with cytotoxic T lymphocytes (CTLs) reactive with specific viral antigens has proven to be effective. Here, the investigators aim to evaluate the safety and efficacy of multiple infusions of HPV specific cytotoxic T lymphocytes cells in patients.

Eligibility criteria: Inclusion Criteria:

1. Written, informed consent obtained prior to any study-specific procedures.
2. Evidence of HPV virus activation (viral DNA) or high risk of HPV infection.
3. Not suitable for routine treatment or invalid to antiviral drugs.
4. Patients with viral disease symptoms and confirmed by biopsy, regardless of the level of virus DNA.
5. Age less than 75 years.
6. Did not use Penicillin or β-lactam antibiotics, or the lowest dose of other antibiotics.
7. Initial hematopoietic reconstitution: neutrophils (ANC) ≥ 1,000/mm\^3, platelet (PLT) ≥ 1,000/mm\^3.
8. Proper renal and hepatic functions (ULN denotes "upper limit of normal range"): Creatinine ≤ 2\*ULN, Bilirubin ≤ 2\*ULN, SGOT/ SGPT ≤ 3\*ULN.
9. If HPV-CTL is not from the patient's own, then the provider of HPV-CTL 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.
10. Human immunodeficiency virus (HIV) test was negative.

Exclusion Criteria:

1. Subject or the donor of BMT recipient infected with HCV (HCV antibody positive), HBV (HBsAg positive), HIV (HIV antibody positive), HTLV (HTLV antibody positive), Treponema pallidum antibody positive or TB culture positive.
2. Subject is albumin-intolerant.
3. Subject with life expectancy less than 8 weeks.
4. Subject participated in other investigational somatic cell therapies within past 30 days.
5. Subject with positive pregnancy test result.

Primary outcomes:
measure: Safety of HPV-CTLs in patients using CTCAE version 4.0 standard to evaluate the level of adverse events
timeFrame: 6 months
Secondary outcomes:
measure: Viral load response
timeFrame: 6 months
measure: Treatment Responses
timeFrame: 1 year
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Shenzhen Geno-immune Medical Institute
state: Guangdong
Study officials:
affiliation: Shenzhen Geno-Immune Medical Institute
name: Lung-Ji Chang, PhD
role: PRINCIPAL_INVESTIGATOR
References: