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E7 TCR T Cell Immunotherapy for High-Grade Cervical Intraepithelial Neoplasia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04411134
Recruitment Status : Withdrawn (Closed based on the lack of perceived clinical activity observed from a different study treating a similar patient population with same study agent.)
First Posted : June 2, 2020
Last Update Posted : July 15, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Tracking Information
First Submitted Date  ICMJE May 30, 2020
First Posted Date  ICMJE June 2, 2020
Last Update Posted Date July 15, 2020
Actual Study Start Date  ICMJE May 28, 2020
Actual Primary Completion Date July 14, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 30, 2020)
To determine the safety of intralesional injection of E7 TCR T cell therapy for highgrade CIN [ Time Frame: 3 months ]
The fraction who experience a DLT based on the dose level and cell administration within the dose level will be determined and reported.The analysis will be entirely descriptive.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE E7 TCR T Cell Immunotherapy for High-Grade Cervical Intraepithelial Neoplasia
Official Title  ICMJE A Phase I Study of E7 TCR T Cell Immunotherapy for High-Grade Cervical Intraepithelial Neoplasia
Brief Summary

Background:

Human papillomavirus (HPV) can lead to High-Grade Cervical Intraepithelial Neoplasia (CIN 2,3). This type of lesion has a high risk of becoming cancer. T cells are part of the immune system. A new type of treatment involves modifying these cells and injecting them into the lesions to shrink them.

Objective:

To test if injecting a type of treatment directly into cervical lesions can be safely given as therapy for high-grade CIN.

Eligibility:

People ages 21 and older with CIN 2,3 caused by HPV-16

Design:

Participants will be screened over at least 2 visits with:

Tumor sample

Blood and urine tests

Medical and medication history

Physical exam

Pelvic exam and colposcopy to look at the cervix

Participants will have a baseline visit. They may be admitted to the hospital. They may receive a large catheter inserted into a vein. They will have a vein assessment.

Before they receive treatment, participants will have a biopsy of the cervix. They will have leukapheresis. Blood will be removed through a needle in the arm, circulated through a machine that takes out the while blood cells, then returned through a needle in the other arm. A central catheter may also be used.

Participants will have the modified cells injected directly into their cervical lesions. They will recover in the hospital for 1-2 days.

Participants will have follow-up visits 2 weeks, 31 days, 6 weeks, and 12 weeks after treatment. They may receive a second injection at the 31-day visit.

Participants will be contacted once a year for 5 years after treatment. They will be followed for up to 15 years.

Detailed Description

Background:

  • Cervical Intraepithelial Neoplasia (CIN) is caused by persistent infection with the Human Papillomavirus (HPV).
  • High-grade lesions are common, affecting 5% of the female population in the United States, and are more likely to progress to cervical cancer.
  • Surgical and ablative therapies are effective but can lead to long-term morbidity. New treatment modalities are needed.
  • E7 TCR T cells have demonstrated safety and clinical activity in treatment-refractory metastatic HPV+ cancers.

Objectives:

- To determine the safety of intralesional injection of E7 TCR T cells as therapy for high- grade CIN.

Eligibility:

- Patients greater than or equal to 21 years of age with HPV16-associated, high-grade CIN.

Design:

  • This is a phase I clinical trial with a 3+3 dose escalation design.
  • Patients will receive intralesional injections of E7 TCR T cells.
  • Patients will not receive a conditioning chemotherapy regimen or systemic aldesleukin.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cervical Intraepithelial Neoplasia
Intervention  ICMJE Biological: E7 TCR
Approximately 3x10^8 or 1.5x10^9 E7 TCR T cells will be injected on day 0 and 1.5x10^9 E7 TCR T cells on day 31 (2 escalating dose levels)
Study Arms  ICMJE
  • Experimental: Arm 1
    Approximately 3x10^8 or 1.5x10^9 E7 TCR T cells will be injected on day 0 and 1.5x10^9 E7 TCR T cells on day 31 (2 escalating dose levels)
    Intervention: Biological: E7 TCR
  • Experimental: Arm 2
    The MTD from among dose level 1 and dose level 2
    Intervention: Biological: E7 TCR
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: July 14, 2020)
0
Original Estimated Enrollment  ICMJE
 (submitted: May 30, 2020)
200
Actual Study Completion Date  ICMJE July 14, 2020
Actual Primary Completion Date July 14, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • INCLUSION CRITERIA:
  • Patients must have histologically confirmed high-grade cervical intraepithelial neoplasia (CIN 2,3). Confirmation of high-grade cervical intraepithelial neoplasia (pathology report from outside institution is sufficient). Pathology confirming high-grade CIN must be within 3 months prior to initiation of study therapy. If needed, confirmatory biopsy of lesion(s) may be performed.
  • HPV16+ CIN 2,3 and HLA-A*02:01 HLA type
  • Patients may be treatment-naive or have received previous treatment for high-grade CIN. Patients who have received previous treatment are eligible if prior treatment was greater than or equal to 3 months before first dose of E7 TCR T cells and there is pathological confirmation of recurrent or persistent disease. If needed, confirmatory biopsy of lesion(s) may be performed.
  • Patients can have either one lesion or multiple lesions with at least one lesion being visible on colposcopy to help facilitate intralesional administration of E7 TCR T cells.
  • Age greater than or equal to 21 years. Because treatment for this disease is not recommended in patients <21 years of age, children and adolescents <21 years old are excluded from this study.
  • ECOG performance status greater than or equal to 2.
  • Patients must have adequate organ and marrow function as defined below:

    • leukocytes greater than or equal to 3,000/mcL
    • absolute neutrophil count greater than or equal to 1,500/mcL
    • platelets greater than or equal to 100,000/mcL
    • total bilirubin within 1.5X normal institutional limits
    • AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper limit of normal
    • creatinine within normal institutional limits
    • creatinine clearance Calculated creatinine clearance (CrCl) >50mL/min/1.73m^2 for patient with creatinine levels above institutional normal (by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation)
  • Women of child-bearing potential must have a negative pregnancy test because E7 TCR T cells have unknown potential for teratogenic or abortifacient effects. Women of childbearing potential are defined as all women who are not post-menopausal or who have not had a hysterectomy. Postmenopausal will be defined as women over the age of 55 who have not had a menstrual period in at least 1 year.
  • The effects of E7 TCR T cells on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception (intrauterine device, hormonal or barrier method of birth control, abstinence, tubal ligation or vasectomy) prior to study entry and for up to 4 months after treatment. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.
  • Seronegative for HIV antibody. The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment.
  • Seronegative for hepatitis B antigen and hepatitis C antibody. If hepatitis C antibody test is positive, then the patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
  • Must be willing to participate in Gene Therapy Long Term Follow up Protocol, which will follow patients for up to 15 years per Food and Drug Administration (FDA) requirements.
  • Ability of subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

  • Patients who are receiving any other investigational agents.
  • Uncontrolled intercurrent illness including, but not limited to, active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with E7 TCR T cells, breastfeeding should be discontinued if the mother is treated with E7 TCR T cells. These potential risks may also apply to other agents used in this study.
  • Patients with any form of systemic immunodeficiency, including acquired deficiency such as HIV or primary immunodeficiency such as Severe Combined Immunodeficiency Disease, are ineligible. The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the treatment.
  • Patients on immunosuppressive drugs including systemic corticosteroids (inhaled or intranasal corticosteroids are allowed).
  • Patients with a second active invasive cancer are not eligible.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 21 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04411134
Other Study ID Numbers  ICMJE 200093
20-C-0093
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Christian S Hinrichs, M.D. National Cancer Institute (NCI)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP