Cervical Intraepithelial NeoplasiaPhase 1NCT04411134
E7 TCR T Cell Immunotherapy for High-Grade Cervical Intraepithelial Neoplasia
A Phase 1 study testing E7 TCR in people with Cervical Intraepithelial Neoplasia, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 years and older, women only
- Conditions the study is for
- Cervical Intraepithelial Neoplasia
- What is being tested?
- E7 TCR
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 28 May 2020to 14 Jul 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Phase I Study of E7 TCR T Cell Immunotherapy for High-Grade Cervical Intraepithelial Neoplasia
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.
Read more
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.
Read the 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.
- Conditions
- Cervical Intraepithelial Neoplasia
- Being tested
- E7 TCR
- Keywords
- T Cell Receptor, Immunotherapy, Human Papillomavirus, Intralesional Injections, Cervical Cancer
- Medical subject headings
- Uterine Cervical Dysplasia, Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
E7 TCRBiological
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 group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | 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) Receives: Biological: E7 TCR |
| Arm 2 | Experimental | The MTD from among dose level 1 and dose level 2 Receives: Biological: E7 TCR |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety of intralesional injection of E7 TCR T cell therapy for highgrade CIN
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.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2020
- Study start28 May 2020
- Primary completion14 Jul 2020
- Study completion14 Jul 2020
Why it stopped: Closed based on the lack of perceived clinical activity observed from a different study treating a similar patient population with same study agent.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cervical Intraepithelial NeoplasiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Christian S Hinrichs, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04411134
- Sponsor's protocol ID
- 200093
- Other IDs
- 20-C-0093
- Status last verified
- Jul 2020
- First submitted
- 30 May 2020
- Last updated
- 15 Jul 2020
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of E7 TCR T Cell Immunotherapy for High-Grade Cervical Intraepithelial Neoplasia
- ClinicalTrials.gov ID
- NCT04411134
- Acronym / sponsor ID
- 200093
- Conditions
- Cervical Intraepithelial Neoplasia
- Keywords
- T Cell Receptor, Immunotherapy, Human Papillomavirus, Intralesional Injections, Cervical Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Closed based on the lack of perceived clinical activity observed from a different study treating a similar patient population with same study agent.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 28 May 2020 (actual)
- Primary completion
- 14 Jul 2020 (actual)
- Study completion
- 14 Jul 2020 (actual)
- First posted
- 2 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Biological: E7 TCRApproximately 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) |
| Arm 2 | Experimental | Biological: E7 TCRThe MTD from among dose level 1 and dose level 2 |
Who may qualify
- Ages
- 21 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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.
Key exclusion criteria (6 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| E7 TCRApproximately 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) | Biological | Arm 1, Arm 2 |
Primary outcome
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.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2020.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Related trials for Cervical Intraepithelial Neoplasia
Active, not recruitingObservational study
Vaginal Microbiome and HPV Pre-malignant and Cervical Dysplasia
Human Papilloma Virus, Vaginal Flora Imbalance
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C2001P-CS3: Testing the Feasibility of Different HPV Screening and Care Strategies for Women Living With HIV
Human Papillomavirus (HPV), HPV Associated Cancers
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Clinical Audit of Cervical Cytology Services in an Early Cancer Detection Unit
Cervical Intraepithelial Neoplasia, Uterine Cervical Neoplasms
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Predictive Biomarkers for Precision Management of Pre-cancerous Cervical Neoplasia
HSIL, High Grade Squamous Intraepithelial Lesion, DNA Methylation
Not yet recruitingPhase 2
Exploratory Study of the Efficacy of HAL-PDT in CIN 3
Cervical Intraepithelial Neoplasia Grade 3
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christian S Hinrichs, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing E7 TCR in people with Cervical Intraepithelial Neoplasia, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the safety of intralesional injection of E7 TCR T cell therapy for highgrade CIN (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2020.