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NCT03197025

Immunotherapy With E6 T Cell Receptor (TCR) T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions

Terminated Phase 1 Results posted Last updated 16 February 2021
What this trial tests

Phase 1 trial testing Aldesleukin in Human Papillomavirus in 1 participant. Terminated before completion.

Timeline
9 January 2018
Primary endpoint
14 May 2019
16 October 2020

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment1
Start date9 January 2018
Primary completion14 May 2019
Estimated completion16 October 2020
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 65, female only, with Human Papillomavirus or HPV-16. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Maximum Tolerated Dose (MTD) of E6 T Cell Receptor (TCR) T Cells for the Treatment of Vulvar High-Grade Squamous Intraepithelial Lesions (HSIL) Primary · within 30 days of cell infusion

MTD is defined as the highest dose at which a maximum of 1 of 6 participants has a dose limiting toxicity (DLT). A DLT is defined as all treatment related Grade 3 (i.e. severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living (ADL)) and greater adverse events occurring within 30 days of the cell infusion with the exception of Grade 3 fever or chills responsive to symptomatic treatment that resolve to ≤ grade 2 in 48 hours. Grade 3 hypotension or oliguria responsiv

GroupValue95% CI
Dose Level -1: 0.7 x 10^10 Transduced T CellsNA
Number of Participants With a Clinical Response Treated With E6 T Cell Receptor (TCR) T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions (HSIL) Secondary · 3 months

Complete Response (CR) is disappearance of all target lesions. No appearance of new lesions. Partial Response (PR) is a ≥50% decrease in the sum of the product of the longest perpendicular diameters of target lesions, taking as reference the baseline measurements. No appearance of new lesions. No increase of greater than 25% of index lesion. Progressive disease is a ≥25% increase in the sum of the product of the longest perpendicular diameters of target lesions, taking as reference the smallest product on study (this includes the baseline product if that is the smallest on study). In addition

GroupValue95% CI
Dose Level -1: 0.7 x 10^10 Transduced T Cells0
Dose Level -1: 0.7 x 10^10 Transduced T Cells0
Dose Level -1: 0.7 x 10^10 Transduced T Cells0
Dose Level -1: 0.7 x 10^10 Transduced T Cells1
Number of Participants With Serious and Non-Serious Adverse Events Secondary · Date treatment consent signed to date off study, approximately 4 months and 17 days.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one o

GroupValue95% CI
Dose Level -1: 0.7 x 10^10 Transduced T Cells1
Number of Grade 4 Lymphocyte Count Decreased Dose Limiting Toxicities (DLT) Secondary · within 30 days of cell infusion

DLT is defined as all treatment related Grade 3 (severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (ADL) and greater adverse events occurring within 30 days of the cell infusion with the exception of the following expected transient effects of aldesleukin. Grade 3 fever or chills responsive to symptomatic treatment that resolve to ≤ grade 2 in 48 hours. Grade 3 hypotension or oliguria responsive to ≤ 1.5L of intravenous fluid boluses in 24 hours that resolv

GroupValue95% CI
Dose Level -1: 0.7 x 10^10 Transduced T Cells1

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, approximately 4 months and 17 days.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dose Level -1: 0.7 x 10^10 Transduced T Cells
Serious: 0/1 (0%)
Deaths: 0/1
Other adverse events (16 terms — click to expand)

ReactionSystemDose Level -1: 0.7 x 10^10…
Abdominal painGastrointestinal disorders
AnxietyPsychiatric disorders
BloatingGastrointestinal disorders
ChillsGeneral disorders
DiarrheaGastrointestinal disorders
Edema faceGeneral disorders
Edema limbsGeneral disorders
Edema trunkGeneral disorders
FatigueGeneral disorders
FeverGeneral disorders
FlushingVascular disorders
HeadacheNervous system disorders
HypophosphatemiaMetabolism and nutrition disorders
Lymphocyte count decreasedInvestigations
Platelet count decreasedInvestigations
Skin ulcerationSkin and subcutaneous tissue disorders

Data from ClinicalTrials.gov NCT03197025 adverse events section.

Sponsor's own description

Background: Vulvar high-grade squamous intraepithelial lesion (HSIL) is caused by infection of the vulva with human papillomavirus (HPV). In a small percentage of cases, vulvar HSIL can turn into cancer. The risk of cancer can be reduced by treating HSIL. A personalized immune treatment might rid the body of HPV infection and thereby cure vulvar HSIL. The immune treatment in this study is called T cell therapy. The cells are E6 T Cell Receptor (TCR) T cells. Participants will also get aldesleukin (IL-2) to help the cells last longer. Objective: To find a safe dose of E6 TCR T cells combined with aldesleukin to use in people with vulvar HSIL. Eligibility: Design: Participants will be screened with: Physical exam Medical history Blood, lab, and pregnancy tests Heart tests Chest x-ray Sample of tissue taken from the vulva (biopsy). Participants will have leukapheresis. Blood will be removed by a needle in one arm. A machine removes white blood cells from the blood. The rest of the blood is returned by needle in the other arm. The white blood cells will be changed into E6 TCR T cells and grown in a lab. About 3 weeks later, participants will be admitted to the hospital for about 5 days. They will get the cells through a tube placed in a vein. They will get IL-2 the same way. Participants will recover 1-3 days in the hospital. They will be monitored closely. They will have blood and lab tests. Participants will have follow-up visits with lab tests and a physical exam every few months for 5 years. At some visits they will also have leukapheresis, blood tests, or vulvar biopsy.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Therapeutic vaccines for high-risk HPV-associated diseases.
    Chabeda A, Yanez RJR, Lamprecht R, Meyers AE, et al · · 2018 · cited 148× · PMID 29277575 · DOI 10.1016/j.pvr.2017.12.006
  2. Evolution of CD8<sup>+</sup> T Cell Receptor (TCR) Engineered Therapies for the Treatment of Cancer.
    Sun Y, Li F, Sonnemann H, Jackson KR, et al · · 2021 · cited 34× · PMID 34572028 · DOI 10.3390/cells10092379
  3. Enhanced clinical-scale manufacturing of TCR transduced T-cells using closed culture system modules.
    Jin J, Gkitsas N, Fellowes VS, Ren J, et al · · 2018 · cited 34× · PMID 29368612 · DOI 10.1186/s12967-018-1384-z
  4. Recent developments in immunotherapy of cancers caused by human papillomaviruses.
    Fakhr E, Modic Ž, Cid-Arregui A. · · 2021 · cited 22× · PMID 33205441 · DOI 10.1111/imm.13285
  5. T-Cell Gene Therapy in Cancer Immunotherapy: Why It Is No Longer Just CARs on The Road.
    Crowther MD, Svane IM, Met Ö, Met Ö. · · 2020 · cited 17× · PMID 32630096 · DOI 10.3390/cells9071588
  6. Engineered T Cell Therapy for Gynecologic Malignancies: Challenges and Opportunities.
    Xu Y, Jiang J, Wang Y, Wang W, et al · · 2021 · cited 14× · PMID 34386017 · DOI 10.3389/fimmu.2021.725330
  7. Current Situation and Prospect of Adoptive Cellular Immunotherapy for Malignancies.
    Zhao D, Zhu D, Cai F, Jiang M, et al · · 2023 · cited 12× · PMID 38037341 · DOI 10.1177/15330338231204198
  8. Gene Augmentation and Editing to Improve TCR Engineered T Cell Therapy against Solid Tumors.
    Lo Presti V, Buitenwerf F, van Til NP, Nierkens S. · · 2020 · cited 11× · PMID 33287413 · DOI 10.3390/vaccines8040733

Verify or expand the search:

Other trials of Aldesleukin

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Trials by the same sponsor.

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