HPV Specific Immune Lymphocytes (HPV-CTLs) in the Treatment of HPV

Phase I/II and Multicenter Trial of HPV Specific Immune Lymphocytes (HPV-CTLs) in the Treatment of Human Papilloma Virus (HPV) Infection

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

Study Overview

• Status: Unknown
• Conditions: Human Papilloma Virus
• Intervention / Treatment: Biological: 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.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Geno-immune Medical Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HPV-CTLs; Autologous or allogenic HPV specific cytotoxic lymphocytes	Biological: HPV-CTLs; 2 to 4 infusions, once a week, for 1x10^5~4x10^6 CTLs/kg by IV each time

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of HPV-CTLs in patients using CTCAE version 4.0 standard to evaluate the level of adverse events	Physiological parameter (measuring cytokine response, fever, symptoms)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral load response	The viral load response to the CTLs infusion will be assessed by HPV specific PCR of peripheral blood.	6 months
Treatment Responses	Disease status is defined by the biochemical markers (measuring HPV concentration and so on) to get the outcomes such as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD).	1 year

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2017
• Primary Completion (Actual): July 31, 2019
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: November 20, 2017
• First Submitted That Met QC Criteria: November 20, 2017
• First Posted (Actual): November 24, 2017

Study Record Updates

• Last Update Posted (Actual): September 19, 2019
• Last Update Submitted That Met QC Criteria: September 18, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Human papilloma virus; Cytotoxic lymphocyte; HPV-CTL
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Papilloma
• Other Study ID Numbers: GIMI-IRB-17020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No