Trial Outcomes & Findings for Immunotherapy With E6 T Cell Receptor (TCR) T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions (NCT NCT03197025)

NCT ID: NCT03197025

Last Updated: 2021-02-16

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

1 participants

Primary outcome timeframe

within 30 days of cell infusion

Results posted on

2021-02-16

Participant Flow

Only one participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.

Participant milestones

Participant milestones
Measure	Dose Level -1: 0.7 x 10^10 Transduced T Cells 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 Study STARTED	1
Overall Study COMPLETED	1
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Level -1: 0.7 x 10^10 Transduced T Cells n=1 Participants 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
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	43.9 years STANDARD_DEVIATION 0 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: within 30 days of cell infusion

Outcome measures

Outcome measures
Measure	Dose Level -1: 0.7 x 10^10 Transduced T Cells n=1 Participants 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
Maximum Tolerated Dose (MTD) of E6 T Cell Receptor (TCR) T Cells for the Treatment of Vulvar High-Grade Squamous Intraepithelial Lesions (HSIL)	NA cells 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).

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	Dose Level -1: 0.7 x 10^10 Transduced T Cells n=1 Participants 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
Number of Participants With a Clinical Response Treated With E6 T Cell Receptor (TCR) T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions (HSIL) Complete Response (CR)	0 Participants
Number of Participants With a Clinical Response Treated With E6 T Cell Receptor (TCR) T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions (HSIL) Partial Response (PR)	0 Participants
Number of Participants With a Clinical Response Treated With E6 T Cell Receptor (TCR) T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions (HSIL) Progressive Disease (PD)	0 Participants
Number of Participants With a Clinical Response Treated With E6 T Cell Receptor (TCR) T Cells for Vulvar High-Grade Squamous Intraepithelial Lesions (HSIL) Non-CR/Non-PD	1 Participants

SECONDARY outcome

Timeframe: 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 of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Dose Level -1: 0.7 x 10^10 Transduced T Cells n=1 Participants 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
Number of Participants With Serious and Non-Serious Adverse Events	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: within 30 days of cell infusion

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Dose Level -1: 0.7 x 10^10 Transduced T Cells n=1 Participants 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
Number of Grade 4 Lymphocyte Count Decreased Dose Limiting Toxicities (DLT)	1 Toxicities

Adverse Events

Dose Level -1: 0.7 x 10^10 Transduced T Cells

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Dose Level -1: 0.7 x 10^10 Transduced T Cells n=1 participants at risk 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
Gastrointestinal disorders Abdominal pain	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 17 days. One participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.
Psychiatric disorders Anxiety	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 17 days. One participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.
Gastrointestinal disorders Bloating	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 17 days. One participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.
General disorders Chills	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 17 days. One participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.
Gastrointestinal disorders Diarrhea	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 17 days. One participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.
General disorders Edema face	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 17 days. One participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.
General disorders Edema limbs	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 17 days. One participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.
General disorders Edema trunk	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 17 days. One participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.
General disorders Fatigue	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 17 days. One participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.
General disorders Fever	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 17 days. One participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.
Vascular disorders Flushing	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 17 days. One participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.
Nervous system disorders Headache	100.0% 1/1 • Number of events 2 • Date treatment consent signed to date off study, approximately 4 months and 17 days. One participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.
Metabolism and nutrition disorders Hypophosphatemia	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 17 days. One participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.
Investigations Lymphocyte count decreased	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 17 days. One participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.
Investigations Platelet count decreased	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 17 days. One participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.
Skin and subcutaneous tissue disorders Skin ulceration	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 4 months and 17 days. One participant was enrolled, thus Arm/Group - 2/Arm 2 MTD was not done.

Additional Information

Scott Norberg, DO

National Cancer Institute

Phone: 301-275-9668

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place