Trial Outcomes & Findings for T Cell Receptor Immunotherapy Targeting HPV-16 E6 for HPV-Associated Cancers (NCT NCT02280811)
NCT ID: NCT02280811
Last Updated: 2017-09-06
Results Overview
The MTD is the highest dose at which ≤1 of 6 patients experienced a dose limiting toxicity (DLT) or the highest dose level studied if DLTs are not observed at any of the dose levels.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
12 participants
Primary outcome timeframe
participants were followed for the duration of hospital stay, an average of 3 weeks
Results posted on
2017-09-06
Participant Flow
Participant milestones
| Measure |
HPV-16 E6 mTCR PBL 1x10^9 + HD IL-2
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL 1x10^10 + HD IL-2
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL 1x10^11 + HD IL-2
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL >1x10^11 up to 2x10^11 + HD IL-2
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL MTD + HD IL-2
This is the phase 2 arm that was treated at the MTD determined in the phase 1 portion.
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
|---|---|---|---|---|---|
|
Drug Administration
STARTED
|
1
|
2
|
1
|
6
|
2
|
|
Drug Administration
COMPLETED
|
1
|
2
|
1
|
6
|
2
|
|
Drug Administration
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
Retreated at the MTD
STARTED
|
0
|
0
|
0
|
0
|
1
|
|
Retreated at the MTD
COMPLETED
|
0
|
0
|
0
|
0
|
1
|
|
Retreated at the MTD
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
T Cell Receptor Immunotherapy Targeting HPV-16 E6 for HPV-Associated Cancers
Baseline characteristics by cohort
| Measure |
HPV-16 E6 mTCR PBL 1x10^9 + HD IL-2
n=1 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL 1x10^10 + HD IL-2
n=2 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL 1x10^11 + HD IL-2
n=1 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL >1x10^11 up to 2x10^11 + HD IL-2
n=6 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL MTD + HD IL-2
n=2 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
5 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
10 Participants
n=10 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
2 Participants
n=10 Participants
|
|
Age, Continuous
|
50.0 years
STANDARD_DEVIATION 0 • n=93 Participants
|
34.5 years
STANDARD_DEVIATION 3.5 • n=4 Participants
|
46.0 years
STANDARD_DEVIATION 0 • n=27 Participants
|
53.5 years
STANDARD_DEVIATION 12.5 • n=483 Participants
|
60.0 years
STANDARD_DEVIATION 14.1 • n=36 Participants
|
50.5 years
STANDARD_DEVIATION 12.7 • n=10 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
5 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
10 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
2 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
1 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
6 Participants
n=483 Participants
|
2 Participants
n=36 Participants
|
11 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
6 Participants
n=483 Participants
|
2 Participants
n=36 Participants
|
11 Participants
n=10 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
1 Participants
n=10 Participants
|
|
Region of Enrollment
United States
|
1 participants
n=93 Participants
|
2 participants
n=4 Participants
|
1 participants
n=27 Participants
|
6 participants
n=483 Participants
|
2 participants
n=36 Participants
|
12 participants
n=10 Participants
|
|
Baseline Cancer Types
Cervical
|
0 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
6 Participants
n=10 Participants
|
|
Baseline Cancer Types
Anal
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
2 Participants
n=483 Participants
|
2 Participants
n=36 Participants
|
4 Participants
n=10 Participants
|
|
Baseline Cancer Types
Oropharyngeal
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
1 Participants
n=10 Participants
|
|
Baseline Cancer Types
Vaginal
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
1 Participants
n=10 Participants
|
PRIMARY outcome
Timeframe: participants were followed for the duration of hospital stay, an average of 3 weeksThe MTD is the highest dose at which ≤1 of 6 patients experienced a dose limiting toxicity (DLT) or the highest dose level studied if DLTs are not observed at any of the dose levels.
Outcome measures
| Measure |
All Treated Subjects
n=10 Participants
All treated subjects who received at least one dose of human papilloma virus (HPV)-16 E6 monoclonal T cell receptor (mTCR) peripheral blood lymphocytes (PBL) 1x10\^9, 1x10\^10,1x10\^11, \>1x10\^11 up to 2x10\^11 + high-dose (HD) interleukin 2 (IL-2) were included.
|
HPV-16 E6 mTCR PBL 1x10^10 + HD IL-2
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL 1x10^11 + HD IL-2
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL >1x10^11 up to 2x10^11 + HD IL-2
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL MTD + HD IL-2
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
|---|---|---|---|---|---|
|
Maximum Tolerated Dose (MTD)
|
2 # of cells x 10^11
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 4 yearsObjective tumor response rate is defined as the number of participants with a complete or partial response per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Outcome measures
| Measure |
All Treated Subjects
n=1 Participants
All treated subjects who received at least one dose of human papilloma virus (HPV)-16 E6 monoclonal T cell receptor (mTCR) peripheral blood lymphocytes (PBL) 1x10\^9, 1x10\^10,1x10\^11, \>1x10\^11 up to 2x10\^11 + high-dose (HD) interleukin 2 (IL-2) were included.
|
HPV-16 E6 mTCR PBL 1x10^10 + HD IL-2
n=2 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL 1x10^11 + HD IL-2
n=1 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL >1x10^11 up to 2x10^11 + HD IL-2
n=6 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL MTD + HD IL-2
n=2 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
|---|---|---|---|---|---|
|
Objective Tumor Response Rate (Complete or Partial Response)
Partial Response (PR)
|
0 participants
|
0 participants
|
0 participants
|
2 participants
|
0 participants
|
|
Objective Tumor Response Rate (Complete or Partial Response)
Complete Response (CR)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: up to one yearDuration of response is measured from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progression is at least a 20% increase in the sum of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Outcome measures
| Measure |
All Treated Subjects
n=1 Participants
All treated subjects who received at least one dose of human papilloma virus (HPV)-16 E6 monoclonal T cell receptor (mTCR) peripheral blood lymphocytes (PBL) 1x10\^9, 1x10\^10,1x10\^11, \>1x10\^11 up to 2x10\^11 + high-dose (HD) interleukin 2 (IL-2) were included.
|
HPV-16 E6 mTCR PBL 1x10^10 + HD IL-2
n=2 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL 1x10^11 + HD IL-2
n=1 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL >1x10^11 up to 2x10^11 + HD IL-2
n=6 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL MTD + HD IL-2
n=2 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
|---|---|---|---|---|---|
|
Duration of Response
|
NA months
Participants had no responses.
|
NA months
Participants had no responses.
|
NA months
Participants had no responses.
|
1.5 months
Interval 0.0 to 6.0
|
NA months
Participants had no responses.
|
SECONDARY outcome
Timeframe: 19 months and 7 daysHere is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v3.0). 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
| Measure |
All Treated Subjects
n=1 Participants
All treated subjects who received at least one dose of human papilloma virus (HPV)-16 E6 monoclonal T cell receptor (mTCR) peripheral blood lymphocytes (PBL) 1x10\^9, 1x10\^10,1x10\^11, \>1x10\^11 up to 2x10\^11 + high-dose (HD) interleukin 2 (IL-2) were included.
|
HPV-16 E6 mTCR PBL 1x10^10 + HD IL-2
n=2 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL 1x10^11 + HD IL-2
n=1 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL >1x10^11 up to 2x10^11 + HD IL-2
n=6 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL MTD + HD IL-2
n=2 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
|---|---|---|---|---|---|
|
Number of Participants With Serious and Non-serious Adverse Events
|
1 Participants
|
2 Participants
|
1 Participants
|
6 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: 19 months and 7 daysA dose limiting toxicity is all Grade 3 and greater toxicities with the exception of myelosuppression, defined as lymphopenia, neutropenia, decreased hemoglobin, and thrombocytopenia, due to chemotherapy preparative regimen. Aldesleukin expected toxicities as defined in Appendix 2 and 3 of the protocol. Expected chemotherapy toxicities as defined in the pharmaceutical information section. Immediate hypersensitivity reactions (excluding symptomatic bronchospasm and grade 4 hypotension) occurring within 2 hours of cell infusion (related to cell infusion) that are reversible to a grade 2 or less within 24 hours of cell administration with standard therapy. Grade 3 fever. Events that are clearly related to the patient's disease.
Outcome measures
| Measure |
All Treated Subjects
n=1 Participants
All treated subjects who received at least one dose of human papilloma virus (HPV)-16 E6 monoclonal T cell receptor (mTCR) peripheral blood lymphocytes (PBL) 1x10\^9, 1x10\^10,1x10\^11, \>1x10\^11 up to 2x10\^11 + high-dose (HD) interleukin 2 (IL-2) were included.
|
HPV-16 E6 mTCR PBL 1x10^10 + HD IL-2
n=2 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL 1x10^11 + HD IL-2
n=1 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL >1x10^11 up to 2x10^11 + HD IL-2
n=6 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL MTD + HD IL-2
n=2 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
|---|---|---|---|---|---|
|
Number of Participants With a Dose Limiting Toxicity (DLT)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: One month after treatmentPopulation: One patient in group HPV-16 E6 mTCR PBL 1x10\^10 + HD IL-2 did not have research blood collected at one month post infusion, and thus could not examine the cells for that patient at that time point.
Detection of E6 TCR T cells in patients peripheral blood leukocytes (PBL)/apheresis samples by flow cytometry.
Outcome measures
| Measure |
All Treated Subjects
n=1 Participants
All treated subjects who received at least one dose of human papilloma virus (HPV)-16 E6 monoclonal T cell receptor (mTCR) peripheral blood lymphocytes (PBL) 1x10\^9, 1x10\^10,1x10\^11, \>1x10\^11 up to 2x10\^11 + high-dose (HD) interleukin 2 (IL-2) were included.
|
HPV-16 E6 mTCR PBL 1x10^10 + HD IL-2
n=1 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL 1x10^11 + HD IL-2
n=1 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL >1x10^11 up to 2x10^11 + HD IL-2
n=6 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL MTD + HD IL-2
n=2 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
|---|---|---|---|---|---|
|
Percentage of Cluster of Differentiation 3 (CD3+) Cells That Are E6 T-Cell Receptor Memory of Circulating T-Cells in Responders and Non-responders
Responders
|
NA percentage of cells
There were no responders in this group so that means they did not have a mean percentage of E6 TCR cells at one month.
|
NA percentage of cells
There were no responders in this group so that means they did not have a mean percentage of E6 TCR cells at one month.
|
NA percentage of cells
There were no responders in this group so that means they did not have a mean percentage of E6 TCR cells at one month.
|
38 percentage of cells
Interval 30.1 to 45.9
|
NA percentage of cells
There were no responders in this group so that means they did not have a mean percentage of E6 TCR cells at one month.
|
|
Percentage of Cluster of Differentiation 3 (CD3+) Cells That Are E6 T-Cell Receptor Memory of Circulating T-Cells in Responders and Non-responders
Non-responders
|
30.7 percentage of cells
Interval 30.7 to 30.7
|
4.4 percentage of cells
Interval 4.4 to 4.4
|
12.6 percentage of cells
Interval 12.6 to 12.6
|
29.9 percentage of cells
Interval 10.4 to 44.4
|
37.1 percentage of cells
Interval 21.7 to 52.5
|
SECONDARY outcome
Timeframe: one month after treatmentPopulation: One patient in group HPV-16 E6 mTCR PBL 1x10\^10 + HD IL-2 did not have research blood collected at one month post infusion, and thus could not examine the cells for that patient at that time point.
Presence of PD-1 on circulating lymphocytes by flow cytometry one month after treatment.
Outcome measures
| Measure |
All Treated Subjects
n=1 Participants
All treated subjects who received at least one dose of human papilloma virus (HPV)-16 E6 monoclonal T cell receptor (mTCR) peripheral blood lymphocytes (PBL) 1x10\^9, 1x10\^10,1x10\^11, \>1x10\^11 up to 2x10\^11 + high-dose (HD) interleukin 2 (IL-2) were included.
|
HPV-16 E6 mTCR PBL 1x10^10 + HD IL-2
n=1 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL 1x10^11 + HD IL-2
n=1 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL >1x10^11 up to 2x10^11 + HD IL-2
n=6 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL MTD + HD IL-2
n=2 Participants
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
|---|---|---|---|---|---|
|
Expression of Programmed Cell Death 1 (PD-1) by Circulating E6 T-Cell Receptor (TCR) T-Cells
|
1 % PD-1 circulating lymphocytes
Interval 1.0 to 1.0
|
2 % PD-1 circulating lymphocytes
Interval 2.0 to 2.0
|
3 % PD-1 circulating lymphocytes
Interval 3.0 to 3.0
|
1 % PD-1 circulating lymphocytes
Interval 0.0 to 3.6
|
2.2 % PD-1 circulating lymphocytes
Interval 0.5 to 3.9
|
Adverse Events
HPV-16 E6 mTCR PBL 1x10^9 + HD IL-2
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
HPV-16 E6 mTCR PBL 1x10^10 + HD IL-2
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
HPV-16 E6 mTCR PBL 1x10^11 + HD IL-2
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
HPV-16 E6 mTCR PBL >1x10^11 up to 2x10^11 + HD IL-2
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
HPV-16 E6 mTCR PBL MTD + HD IL-2
Serious events: 2 serious events
Other events: 2 other events
Deaths: 0 deaths
HPV-16 E6 mTCR PBL MTD + HD IL-2-Retreatment
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
HPV-16 E6 mTCR PBL 1x10^9 + HD IL-2
n=1 participants at risk
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL 1x10^10 + HD IL-2
n=2 participants at risk
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL 1x10^11 + HD IL-2
n=1 participants at risk
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL >1x10^11 up to 2x10^11 + HD IL-2
n=6 participants at risk
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL MTD + HD IL-2
n=2 participants at risk
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL MTD + HD IL-2-Retreatment
n=1 participants at risk
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
|---|---|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
0.00%
0/1 • 19 months and 7 days
|
50.0%
1/2 • Number of events 1 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/6 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory::Bronchopulmonary NOS
|
0.00%
0/1 • 19 months and 7 days
|
50.0%
1/2 • Number of events 1 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/6 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/1 • 19 months and 7 days
|
50.0%
1/2 • Number of events 1 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/6 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Respiratory, thoracic and mediastinal disorders
Obstruction/stenosis of airway::Bronchus
|
0.00%
0/1 • 19 months and 7 days
|
50.0%
1/2 • Number of events 1 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/6 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Respiratory, thoracic and mediastinal disorders
Prolonged intubation after pulmonary resection (>24 hrs after surgery)
|
0.00%
0/1 • 19 months and 7 days
|
50.0%
1/2 • Number of events 1 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/6 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
16.7%
1/6 • Number of events 1 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Infections and infestations
Infection (documented clinically or microbiologically)
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
33.3%
2/6 • Number of events 2 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Infections and infestations
Febrile neutropenia
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/6 • 19 months and 7 days
|
100.0%
2/2 • Number of events 2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
Other adverse events
| Measure |
HPV-16 E6 mTCR PBL 1x10^9 + HD IL-2
n=1 participants at risk
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL 1x10^10 + HD IL-2
n=2 participants at risk
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL 1x10^11 + HD IL-2
n=1 participants at risk
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL >1x10^11 up to 2x10^11 + HD IL-2
n=6 participants at risk
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL MTD + HD IL-2
n=2 participants at risk
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
HPV-16 E6 mTCR PBL MTD + HD IL-2-Retreatment
n=1 participants at risk
patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
E6 TCR: On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin: Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
|
|---|---|---|---|---|---|---|
|
General disorders
Fatigue
|
100.0%
1/1 • Number of events 1 • 19 months and 7 days
|
50.0%
1/2 • Number of events 1 • 19 months and 7 days
|
100.0%
1/1 • Number of events 1 • 19 months and 7 days
|
16.7%
1/6 • Number of events 1 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Metabolism and nutrition disorders
Hemoglobin
|
100.0%
1/1 • Number of events 1 • 19 months and 7 days
|
100.0%
2/2 • Number of events 2 • 19 months and 7 days
|
100.0%
1/1 • Number of events 1 • 19 months and 7 days
|
66.7%
4/6 • Number of events 4 • 19 months and 7 days
|
100.0%
2/2 • Number of events 2 • 19 months and 7 days
|
100.0%
1/1 • Number of events 1 • 19 months and 7 days
|
|
Infections and infestations
Infection (documented clinically and microbiologically)
|
100.0%
1/1 • Number of events 1 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
16.7%
1/6 • Number of events 1 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Blood and lymphatic system disorders
Lymphopenia
|
100.0%
1/1 • Number of events 1 • 19 months and 7 days
|
100.0%
2/2 • Number of events 2 • 19 months and 7 days
|
100.0%
1/1 • Number of events 1 • 19 months and 7 days
|
100.0%
6/6 • Number of events 6 • 19 months and 7 days
|
100.0%
2/2 • Number of events 2 • 19 months and 7 days
|
100.0%
1/1 • Number of events 1 • 19 months and 7 days
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
100.0%
1/1 • Number of events 1 • 19 months and 7 days
|
100.0%
2/2 • Number of events 2 • 19 months and 7 days
|
100.0%
1/1 • Number of events 1 • 19 months and 7 days
|
100.0%
6/6 • Number of events 6 • 19 months and 7 days
|
100.0%
2/2 • Number of events 2 • 19 months and 7 days
|
100.0%
1/1 • Number of events 1 • 19 months and 7 days
|
|
Blood and lymphatic system disorders
Platelets
|
100.0%
1/1 • Number of events 1 • 19 months and 7 days
|
100.0%
2/2 • Number of events 2 • 19 months and 7 days
|
100.0%
1/1 • Number of events 1 • 19 months and 7 days
|
100.0%
6/6 • Number of events 6 • 19 months and 7 days
|
100.0%
2/2 • Number of events 2 • 19 months and 7 days
|
100.0%
1/1 • Number of events 1 • 19 months and 7 days
|
|
Metabolism and nutrition disorders
Bilirubin (hyperbilirubinemia)
|
0.00%
0/1 • 19 months and 7 days
|
50.0%
1/2 • Number of events 1 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/6 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Infections and infestations
Febrile neutropenia
|
0.00%
0/1 • 19 months and 7 days
|
50.0%
1/2 • Number of events 1 • 19 months and 7 days
|
100.0%
1/1 • Number of events 1 • 19 months and 7 days
|
16.7%
1/6 • Number of events 1 • 19 months and 7 days
|
100.0%
2/2 • Number of events 2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Nervous system disorders
Psychosis (hallucinations/delusions)
|
0.00%
0/1 • 19 months and 7 days
|
50.0%
1/2 • Number of events 1 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/6 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
0.00%
0/1 • 19 months and 7 days
|
50.0%
1/2 • Number of events 1 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/6 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Cardiac disorders
Hypotension
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
100.0%
1/1 • Number of events 1 • 19 months and 7 days
|
0.00%
0/6 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Metabolism and nutrition disorders
Creatinine
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
16.7%
1/6 • Number of events 1 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
33.3%
2/6 • Number of events 2 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
33.3%
2/6 • Number of events 2 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Cardiac disorders
Supraventricular and nodal arrhythmia::Sinus tachycardia
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
16.7%
1/6 • Number of events 1 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Nervous system disorders
Syncope (fainting)
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
16.7%
1/6 • Number of events 1 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Renal and urinary disorders
Renal/Genitourinary - Other, Acute renal injury
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/6 • 19 months and 7 days
|
50.0%
1/2 • Number of events 1 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion (non-malignant)
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/6 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/1 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
16.7%
1/6 • Number of events 1 • 19 months and 7 days
|
0.00%
0/2 • 19 months and 7 days
|
0.00%
0/1 • 19 months and 7 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place