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

Human Papilloma Virus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03351855
• Other study ID #: GIMI-IRB-17020
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 15, 2017
• Est. completion date: December 31, 2021

Study information

• Verified date: September 2019
• Source: Shenzhen Geno-Immune Medical Institute
• Contact: Lung-Ji Chang, PhD
• Phone: 86-075586725195
• Email: c[@]szgimi.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2021
• Est. primary completion date: July 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 75 Years

Eligibility

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 ß-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 ß-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.

Related Conditions & MeSH terms

• Human Papilloma Virus
• Papilloma

Intervention

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

Locations

Country	Name	City	State
China	Shenzhen Geno-immune Medical Institute	Shenzhen	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Shenzhen Geno-Immune Medical Institute

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Viral load response	The viral load response to the CTLs infusion will be assessed by HPV specific PCR of peripheral blood.	6 months
Secondary	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