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

Overview

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.

Interventions

• Biological HPV-CTLs
  2 to 4 infusions, once a week, for 1x10\^5\~4x10\^6 CTLs/kg by IV each time

Primary outcome measures

• Safety of HPV-CTLs in patients using CTCAE version 4.0 standard to evaluate the level of adverse events [Time frame: 6 months]

Secondary outcome measures (2)

• Viral load response [Time frame: 6 months]
• Treatment Responses [Time frame: 1 year]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• 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.
• Subject is albumin-intolerant.
• Subject with life expectancy less than 8 weeks.
• Subject participated in other investigational somatic cell therapies within past 30 days.
• Subject with positive pregnancy test result.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shenzhen Geno-immune Medical Institute — Shenzhen

Identifiers

NCT: NCT03351855 · GIMI-IRB-17020

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗