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

• ClinicalTrials.gov Identifier: NCT03351855
• Recruitment Status: Unknown
• First Posted: November 24, 2017
• Last Update Posted: September 19, 2019
• Sponsor: Shenzhen Geno-Immune Medical Institute
• Information provided by (Responsible Party): Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute

Tracking Information

• First Submitted Date: November 20, 2017
• First Posted Date: November 24, 2017
• Last Update Posted Date: September 19, 2019
• Actual Study Start Date: November 15, 2017
• Actual Primary Completion Date: July 31, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 20, 2017)

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

Physiological parameter (measuring cytokine response, fever, symptoms)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 20, 2017)

• Viral load response [ Time Frame: 6 months ]
  The viral load response to the CTLs infusion will be assessed by HPV specific PCR of peripheral blood.
• Treatment Responses [ Time Frame: 1 year ]
  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).

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Human Papilloma Virus

Intervention

Biological: HPV-CTLs

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

Study Arms

Experimental: HPV-CTLs

Autologous or allogenic HPV specific cytotoxic lymphocytes

Intervention: Biological: HPV-CTLs

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: November 20, 2017): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2021
• Actual Primary Completion Date: July 31, 2019 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Months to 75 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03351855
• Other Study ID Numbers: GIMI-IRB-17020
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Shenzhen Geno-Immune Medical Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Lung-Ji Chang, PhD; Shenzhen Geno-Immune Medical Institute

• PRS Account: Shenzhen Geno-Immune Medical Institute
• Verification Date: September 2019