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

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ClinicalTrials.gov Identifier: NCT03197025
Recruitment Status : Terminated (The study was closed due to investigator discretion based on the lack of perceived clinical activity observed in the study.)
First Posted : June 23, 2017
Results First Posted : October 8, 2019
Last Update Posted : February 16, 2021
Sponsor:
Information provided by (Responsible Party):
Scott Norberg, D.O., National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Human Papillomavirus
HPV-16
High Grade Squamous Intraepithelial Lesion
Interventions Drug: Aldesleukin
Biological: E6 T Cell Receptor (TCR)
Enrollment 1
Recruitment Details  
Pre-assignment Details Only one participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.
Arm/Group Title Dose Level -1: 0.7 x 10^10 Transduced T Cells
Hide Arm/Group Description

Patients will undergo leukapheresis, then treatment with E6 T Cell Receptor (TCR) cells (at escalating doses) + aldesleukin

Aldesleukin: Aldesleukin 720,000 IU/kg (based on total body weight) intravenous (IV) infused over 15 minutes approximately every 12 hours for a maximum of two doses.

E6 T Cell Receptor (TCR): On day 0, the E6 TCR cells will be administered one time, intravenously over 20 to 30 minutes

Period Title: Overall Study
Started 1
Completed 1
Not Completed 0
Arm/Group Title Dose Level -1: 0.7 x 10^10 Transduced T Cells
Hide Arm/Group Description

Patients will undergo leukapheresis, then treatment with E6 T Cell Receptor (TCR) cells (at escalating doses) + aldesleukin

Aldesleukin: Aldesleukin 720,000 IU/kg (based on total body weight) intravenous (IV) infused over 15 minutes approximately every 12 hours for a maximum of two doses.

E6 T Cell Receptor (TCR): On day 0, the E6 TCR cells will be administered one time, intravenously over 20 to 30 minutes

Overall Number of Baseline Participants 1
Hide Baseline Analysis Population Description
One participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1 participants
<=18 years
0
   0.0%
Between 18 and 65 years
1
 100.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1 participants
43.9  (0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1 participants
Female
1
 100.0%
Male
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
1
 100.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
1
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 1 participants
1
 100.0%
1.Primary Outcome
Title Maximum Tolerated Dose (MTD) of E6 T Cell Receptor (TCR) T Cells for the Treatment of Vulvar High-Grade Squamous Intraepithelial Lesions (HSIL)
Hide Description 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 responsive to ≤ 1.5L of intravenous fluid boluses in 24 hours that resolves to ≤ grade 2 in 48 hours. Grade 3 dyspnea/hypoxia that improves to ≤ grade 2 or less with supplemental oxygen and resolves to ≤ grade 2 without supplemental oxygen in 48 hours. Grade 3 creatinine or electrolyte abnormalities that resolve to ≤ grade 2 in 48 hours.
Time Frame within 30 days of cell infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dose Level -1: 0.7 x 10^10 Transduced T Cells
Hide Arm/Group Description:

Patients will undergo leukapheresis, then treatment with E6 T Cell Receptor (TCR) cells (at escalating doses) + aldesleukin

Aldesleukin: Aldesleukin 720,000 IU/kg (based on total body weight) intravenous (IV) infused over 15 minutes approximately every 12 hours for a maximum of two doses.

E6 T Cell Receptor (TCR): On day 0, the E6 TCR cells will be administered one time, intravenously over 20 to 30 minutes

Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: cells
NA [1] 
[1]
One patient was analyzed in an attempt to determine the MTD. However, since there was only one patient treated, the primary outcome cannot be measured (since the outcome was determining the MTD).
2.Secondary Outcome
Title Number of Participants With a Clinical Response Treated With E6 T Cell Receptor (TCR) T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions (HSIL)
Hide Description 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 to the relative increase of 25%, the sum must also demonstrate an absolute increase of at least 5mm. (Note: the appearance of one or more new lesions is also considered progression. Non-CR/Non-PD is neither sufficient decrease to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest product of diameters while on study.
Time Frame 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dose Level -1: 0.7 x 10^10 Transduced T Cells
Hide Arm/Group Description:

Patients will undergo leukapheresis, then treatment with E6 T Cell Receptor (TCR) cells (at escalating doses) + aldesleukin

Aldesleukin: Aldesleukin 720,000 IU/kg (based on total body weight) intravenous (IV) infused over 15 minutes approximately every 12 hours for a maximum of two doses.

E6 T Cell Receptor (TCR): On day 0, the E6 TCR cells will be administered one time, intravenously over 20 to 30 minutes

Overall Number of Participants Analyzed 1
Measure Type: Count of Participants
Unit of Measure: Participants
Complete Response (CR)
0
   0.0%
Partial Response (PR)
0
   0.0%
Progressive Disease (PD)
0
   0.0%
Non-CR/Non-PD
1
 100.0%
3.Secondary Outcome
Title Number of Participants With Serious and Non-Serious Adverse Events
Hide Description 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 of the previous outcomes mentioned.
Time Frame Date treatment consent signed to date off study, approximately 4 months and 17 days.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dose Level -1: 0.7 x 10^10 Transduced T Cells
Hide Arm/Group Description:

Patients will undergo leukapheresis, then treatment with E6 T Cell Receptor (TCR) cells (at escalating doses) + aldesleukin

Aldesleukin: Aldesleukin 720,000 IU/kg (based on total body weight) intravenous (IV) infused over 15 minutes approximately every 12 hours for a maximum of two doses.

E6 T Cell Receptor (TCR): On day 0, the E6 TCR cells will be administered one time, intravenously over 20 to 30 minutes

Overall Number of Participants Analyzed 1
Measure Type: Count of Participants
Unit of Measure: Participants
1
 100.0%
4.Other Pre-specified Outcome
Title Number of Grade 4 Lymphocyte Count Decreased Dose Limiting Toxicities (DLT)
Hide Description 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 resolves to ≤ grade 2 in 48 hours. Grade 3 dyspnea/hypoxia that improves to ≤ grade 2 or less with supplemental oxygen and resolves to ≤ grade 2 without supplemental oxygen in 48 hours. Grade 3 creatinine or electrolyte abnormalities that resolve to ≤ grade 2 in 48 hours.
Time Frame within 30 days of cell infusion
Hide Outcome Measure Data
Hide Analysis Population Description
The protocol was amended to exclude Grade 3 or higher white blood cell count decreased/lymphocyte count decreased that resolved to less than Grade 2 in 72 hours. This was done since transient lymphopenia is not a clinically significant event.
Arm/Group Title Dose Level -1: 0.7 x 10^10 Transduced T Cells
Hide Arm/Group Description:

Patients will undergo leukapheresis, then treatment with E6 T Cell Receptor (TCR) cells (at escalating doses) + aldesleukin

Aldesleukin: Aldesleukin 720,000 IU/kg (based on total body weight) intravenous (IV) infused over 15 minutes approximately every 12 hours for a maximum of two doses.

E6 T Cell Receptor (TCR): On day 0, the E6 TCR cells will be administered one time, intravenously over 20 to 30 minutes

Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: Toxicities
1
Time Frame Date treatment consent signed to date off study, approximately 4 months and 17 days.
Adverse Event Reporting Description One participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.
 
Arm/Group Title Dose Level -1: 0.7 x 10^10 Transduced T Cells
Hide Arm/Group Description

Patients will undergo leukapheresis, then treatment with E6 T Cell Receptor (TCR) cells (at escalating doses) + aldesleukin

Aldesleukin: Aldesleukin 720,000 IU/kg (based on total body weight) intravenous (IV) infused over 15 minutes approximately every 12 hours for a maximum of two doses.

E6 T Cell Receptor (TCR): On day 0, the E6 TCR cells will be administered one time, intravenously over 20 to 30 minutes

All-Cause Mortality
Dose Level -1: 0.7 x 10^10 Transduced T Cells
Affected / at Risk (%)
Total   0/1 (0.00%)    
Hide Serious Adverse Events
Dose Level -1: 0.7 x 10^10 Transduced T Cells
Affected / at Risk (%) # Events
Total   0/1 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Dose Level -1: 0.7 x 10^10 Transduced T Cells
Affected / at Risk (%) # Events
Total   1/1 (100.00%)    
Gastrointestinal disorders   
Abdominal pain  1  1/1 (100.00%)  1
Bloating  1  1/1 (100.00%)  1
Diarrhea  1  1/1 (100.00%)  1
General disorders   
Chills  1  1/1 (100.00%)  1
Edema face  1  1/1 (100.00%)  1
Edema limbs  1  1/1 (100.00%)  1
Edema trunk  1  1/1 (100.00%)  1
Fatigue  1  1/1 (100.00%)  1
Fever  1  1/1 (100.00%)  1
Investigations   
Lymphocyte count decreased  1  1/1 (100.00%)  1
Platelet count decreased  1  1/1 (100.00%)  1
Metabolism and nutrition disorders   
Hypophosphatemia  1  1/1 (100.00%)  1
Nervous system disorders   
Headache  1  1/1 (100.00%)  2
Psychiatric disorders   
Anxiety  1  1/1 (100.00%)  1
Skin and subcutaneous tissue disorders   
Skin ulceration  1  1/1 (100.00%)  1
Vascular disorders   
Flushing  1  1/1 (100.00%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Scott Norberg, DO
Organization: National Cancer Institute
Phone: 301-275-9668
EMail: scott.norberg@mail.nih.gov
Layout table for additonal information
Responsible Party: Scott Norberg, D.O., National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03197025    
Other Study ID Numbers: 170116
17-C-0116
First Submitted: June 22, 2017
First Posted: June 23, 2017
Results First Submitted: September 20, 2019
Results First Posted: October 8, 2019
Last Update Posted: February 16, 2021