Trial Outcomes & Findings for Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Melanoma (NCT NCT01993719)
NCT ID: NCT01993719
Last Updated: 2023-01-18
Results Overview
Number of participants with Grades 3-5 treatment-related adverse events were compared in Arm 1N and Arm 1P; and adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 3 is severe. Grade 4 is life-threatening, and Grade 5 is death related to adverse event.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
33 participants
Primary outcome timeframe
30 days after end of treatment
Results posted on
2023-01-18
Participant Flow
Participant milestones
| Measure |
Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen in participants without prior treatment pembrolizumab or nivolumab Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Standard Chemo Prep Regimen Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen in participants previously treated with pembrolizumab or nivolumab.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Decreased Chemo Prep Regimen+Retreat. Young TIL+High Dose Interleukin-2, Decreased Chemo Preparative Regimen. Young TIL+High Dose Interleukin-2, Standard Chemo (Retreat). Lower dose preparative regimen + Young TIL Cells. Aldesleukin: 720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days. Cyclophosphamide: Days -5 to -3 (low-dose arm): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused IV. Retreatment: Standard Chemo Prep Regimen. Aldesleukin: 720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days. Cyclophosphamide: 60 mg/kg/day X 2 days IV. Young TIL: Day 0: Cells will be infused IV.
|
Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Decreased Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2 Lower Dose preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days Cyclophosphamide: Days -5 to -3 (low-dose arm): Cyclophosphamide 30 mg/kg IV over 60 minutes for 2 days.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Standard Chemo Prep Regimen(SCPR)+Retreat. Young TIL+High Dose(HD) Interleukin-2, SCPR. Young TIL+HD Interleukin-2, SC(Retreat). SCPR+Young TIL Cells retreatment with SCPR+Young TIL Cells+pembrolizumab. Aldesleukin:720,000 IU/kgIV every eight hours (+/-1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine:25 mg/m\^2/day intravenous piggy-back(IVPB) daily for 5 days. Cyclophosphamide:60 mg/kg/day X 2 days IV. Young TIL:Day 0: Cells will be infused IV. Retreatment with standard preparative regimen+Young TIL Cells+pembrolizumab. Aldesleukin:720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine:25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days. Cyclophosphamide:60 mg/kg/day X 2 days IV. Young TIL: Day 0:Cells will be infused IV. Pembrolizumab:2 mg/kg IV on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
|---|---|---|---|---|---|
|
First Drug Administration
STARTED
|
8
|
11
|
3
|
9
|
2
|
|
First Drug Administration
COMPLETED
|
7
|
11
|
3
|
9
|
2
|
|
First Drug Administration
NOT COMPLETED
|
1
|
0
|
0
|
0
|
0
|
|
Retreatment After First Drug Administrat
STARTED
|
0
|
0
|
3
|
0
|
2
|
|
Retreatment After First Drug Administrat
COMPLETED
|
0
|
0
|
3
|
0
|
2
|
|
Retreatment After First Drug Administrat
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen in participants without prior treatment pembrolizumab or nivolumab Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Standard Chemo Prep Regimen Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen in participants previously treated with pembrolizumab or nivolumab.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Decreased Chemo Prep Regimen+Retreat. Young TIL+High Dose Interleukin-2, Decreased Chemo Preparative Regimen. Young TIL+High Dose Interleukin-2, Standard Chemo (Retreat). Lower dose preparative regimen + Young TIL Cells. Aldesleukin: 720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days. Cyclophosphamide: Days -5 to -3 (low-dose arm): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused IV. Retreatment: Standard Chemo Prep Regimen. Aldesleukin: 720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days. Cyclophosphamide: 60 mg/kg/day X 2 days IV. Young TIL: Day 0: Cells will be infused IV.
|
Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Decreased Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2 Lower Dose preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days Cyclophosphamide: Days -5 to -3 (low-dose arm): Cyclophosphamide 30 mg/kg IV over 60 minutes for 2 days.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Standard Chemo Prep Regimen(SCPR)+Retreat. Young TIL+High Dose(HD) Interleukin-2, SCPR. Young TIL+HD Interleukin-2, SC(Retreat). SCPR+Young TIL Cells retreatment with SCPR+Young TIL Cells+pembrolizumab. Aldesleukin:720,000 IU/kgIV every eight hours (+/-1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine:25 mg/m\^2/day intravenous piggy-back(IVPB) daily for 5 days. Cyclophosphamide:60 mg/kg/day X 2 days IV. Young TIL:Day 0: Cells will be infused IV. Retreatment with standard preparative regimen+Young TIL Cells+pembrolizumab. Aldesleukin:720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine:25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days. Cyclophosphamide:60 mg/kg/day X 2 days IV. Young TIL: Day 0:Cells will be infused IV. Pembrolizumab:2 mg/kg IV on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
|---|---|---|---|---|---|
|
First Drug Administration
Not treated
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Melanoma
Baseline characteristics by cohort
| Measure |
Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
n=8 Participants
Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen in participants without prior treatment pembrolizumab or nivolumab Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
n=11 Participants
Standard Chemo Prep Regimen Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen in participants previously treated with pembrolizumab or nivolumab.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
n=3 Participants
Decreased Chemo Prep Regimen+Retreat. Young TIL+High Dose Interleukin-2, Decreased Chemo Preparative Regimen. Young TIL+High Dose Interleukin-2, Standard Chemo (Retreat). Lower dose preparative regimen + Young TIL Cells. Aldesleukin: 720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days. Cyclophosphamide: Days -5 to -3 (low-dose arm): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused IV. Retreatment: Standard Chemo Prep Regimen. Aldesleukin: 720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days. Cyclophosphamide: 60 mg/kg/day X 2 days IV. Young TIL: Day 0: Cells will be infused IV.
|
Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
n=9 Participants
Decreased Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2 Lower Dose preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days Cyclophosphamide: Days -5 to -3 (low-dose arm): Cyclophosphamide 30 mg/kg IV over 60 minutes for 2 days.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
n=2 Participants
Standard Chemo Prep Regimen(SCPR)+Retreat. Young TIL+High Dose(HD) Interleukin-2, SCPR. Young TIL+HD Interleukin-2, SC(Retreat). SCPR+Young TIL Cells retreatment with SCPR+Young TIL Cells+pembrolizumab. Aldesleukin:720,000 IU/kgIV every eight hours (+/-1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine:25 mg/m\^2/day intravenous piggy-back(IVPB) daily for 5 days. Cyclophosphamide:60 mg/kg/day X 2 days IV. Young TIL:Day 0: Cells will be infused IV. Retreatment with standard preparative regimen+Young TIL Cells+pembrolizumab. Aldesleukin:720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine:25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days. Cyclophosphamide:60 mg/kg/day X 2 days IV. Young TIL: Day 0:Cells will be infused IV. Pembrolizumab:2 mg/kg IV on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Total
n=33 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
8 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
32 Participants
n=8 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
|
Age, Continuous
|
46.28 years
STANDARD_DEVIATION 1.43 • n=5 Participants
|
56.28 years
STANDARD_DEVIATION 13.39 • n=7 Participants
|
31.07 years
STANDARD_DEVIATION 13.25 • n=5 Participants
|
44.72 years
STANDARD_DEVIATION 3.66 • n=4 Participants
|
53 years
STANDARD_DEVIATION 3.39 • n=21 Participants
|
46.45 years
STANDARD_DEVIATION 13.97 • n=8 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
11 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
22 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
33 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
33 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Region of Enrollment
United States
|
8 participants
n=5 Participants
|
11 participants
n=7 Participants
|
3 participants
n=5 Participants
|
9 participants
n=4 Participants
|
2 participants
n=21 Participants
|
33 participants
n=8 Participants
|
PRIMARY outcome
Timeframe: 30 days after end of treatmentPopulation: One participant was not treated on Arm 1N. Pre-specified by the protocol, there are two combined reporting groups for this outcome. The first combined group (n=23) is all who received standard chemo (Arm 1N, Arm 1P, the retreatment of Arm 2/1P, and the initial treatment of Arm 1P/R). The second combined group (n=12) is all who received the reduced dose chemo (Arm 2, and the initial treatment of Arm 2/1P) This separates reporting of adverse events by the intensity of chemotherapy.
Number of participants with Grades 3-5 treatment-related adverse events were compared in Arm 1N and Arm 1P; and adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 3 is severe. Grade 4 is life-threatening, and Grade 5 is death related to adverse event.
Outcome measures
| Measure |
Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=23 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=23 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=23 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=23 Participants
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=23 Participants
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=23 Participants
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=23 Participants
Grade 5 is death related to adverse event.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Possibly Related Arm 2, Arm 2/1P
n=12 Participants
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 3 - Probably Related Arm 2, Arm 2/1P
n=12 Participants
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 3 - Definitely Related Arm 2, Arm 2/1P
n=12 Participants
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Possibly Related Arm 2, Arm 2/1P
n=12 Participants
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Probably Related Arm 2, Arm 2/1P
n=12 Participants
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Definitely Related Arm 2, Arm 2/1P
n=12 Participants
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P
n=12 Participants
Grade 5 is death related to adverse event.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Hypoxia
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Renal failure
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Renal/Genitourinary - Other (Specify, oliguria)
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Uric acid, serum-high (hyperuricemia)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Vomiting
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Weight loss
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
ALT, SGPT (serum glutamic pyruvic transaminase)
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
AST, SGOT(serum glutamic oxaloacetic transaminase)
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Allergic reaction/hypersensitivity (including drug fever)
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Bilirubin (hyperbilirubinemia)
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Confusion
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Creatinine
|
0 Participants
|
1 Participants
|
3 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Diarrhea
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Febrile neutropenia
|
0 Participants
|
3 Participants
|
4 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Hemoglobin
|
4 Participants
|
2 Participants
|
6 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
3 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Hemorrhage, GU::Vagina
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Hypotension
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Infection (documented clinically or microbiologically) w/Grade 3/4 neutrophils(ANC <1.0x10e9/L)Blood
|
1 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Left ventricular systolic dysfunction
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Leukocytes (total WBC)
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Lymphopenia
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
2 Participants
|
14 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
9 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Nausea
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Neutrophils/granulocytes (ANC/AGC)
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
14 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
4 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
PTT (Partial Thromboplastin Time)
|
0 Participants
|
2 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Phosphate, serum-low (hypophosphatemia)
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment-related Grade 3-5 Adverse Events in Arm 1N and Arm 1P
Platelets
|
0 Participants
|
1 Participants
|
4 Participants
|
0 Participants
|
0 Participants
|
11 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: 4 weeks after cell infusion, then every 3 months x 3 and then every 6 months for 5 years, then per Principal Investigator (PI) discretion up to 5 years or disease progressionPopulation: The first combined group (n=16) is Arm 1P, the second treatment of Arm 2/1P, the initial treatment of Arm 1P/R. The second group (n=7) is Arm 1N (1/8 participants was not treated). The third group (n=12) is Arm 2 and the initial treatment of Arm 2/1P. The final group (n=2) will report the second treatment of Arm 1P/R. This enables reporting of the 37 treatments among the 32 treated participants separated by exposure to pembrolizumab/nivolumab and chemo dose.
Clinical response to treatment was assessed by the Response Evaluation Criteria In Solid Tumors (RECIST v1.0). Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progressive Disease (PD) is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD.
Outcome measures
| Measure |
Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=16 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=7 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=12 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=2 Participants
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 5 is death related to adverse event.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Possibly Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 3 - Probably Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 3 - Definitely Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Possibly Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Probably Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Definitely Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P
Grade 5 is death related to adverse event.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression)
First Treatment - Complete Response
|
0 Participants
|
2 Participants
|
0 Participants
|
NA Participants
Participants in this group evaluated for second treatment only.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression)
First Treatment - Partial Response
|
2 Participants
|
2 Participants
|
2 Participants
|
NA Participants
Participants in this group evaluated for second treatment only.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression)
First Treatment - Progressive Disease
|
8 Participants
|
2 Participants
|
0 Participants
|
NA Participants
Participants in this group evaluated for second treatment only.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression)
First Treatment - Stable Disease
|
3 Participants
|
1 Participants
|
1 Participants
|
NA Participants
Participants in this group evaluated for second treatment only.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression)
Second Treatment - Complete Response
|
0 Participants
|
NA Participants
Participants in this group evaluated for first treatment only.
|
NA Participants
Participants in this group evaluated for first treatment only.
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression)
Second Treatment - Partial Response
|
1 Participants
|
NA Participants
Participants in this group evaluated for first treatment only.
|
NA Participants
Participants in this group evaluated for first treatment only.
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression)
Second Treatment - Progressive Disease
|
1 Participants
|
NA Participants
Participants in this group evaluated for first treatment only.
|
NA Participants
Participants in this group evaluated for first treatment only.
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Have a Clinical Response to Treatment (Objective Tumor Regression)
Second Treatment - Stable Disease
|
1 Participants
|
NA Participants
Participants in this group evaluated for first treatment only.
|
NA Participants
Participants in this group evaluated for first treatment only.
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Date of cells until time of disease progression, up to approximately 67.2 months.Population: Retreat Arm 1N and Arm 2 Foll By Arm 1P not treated.
Overall response is the best response recorded from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.0). Progression is at least a 20% increase in the sum of LD 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 |
Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=16 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=7 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=12 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=2 Participants
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 5 is death related to adverse event.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Possibly Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 3 - Probably Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 3 - Definitely Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Possibly Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Probably Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Definitely Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P
Grade 5 is death related to adverse event.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Response Rate (ORR)
Initial Treatment
|
23.10 percentage of participants
Interval 8.2 to 50.3
|
57.10 percentage of participants
Interval 25.0 to 84.1
|
16.70 percentage of participants
Interval 3.0 to 44.8
|
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—
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—
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—
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—
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—
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—
|
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Overall Response Rate (ORR)
Retreat
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33.30 percentage of participants
Interval 1.7 to 88.2
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50 percentage of participants
Interval 2.6 to 97.4
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SECONDARY outcome
Timeframe: Date treatment consent signed until approximately 4 weeks following last dose of Pembrolizumab, up to 4 weeksNumber of treatment-related adverse events for participants who received pembrolizumab. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Outcome measures
| Measure |
Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=2 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 5 is death related to adverse event.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Possibly Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 3 - Probably Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 3 - Definitely Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Possibly Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Probably Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Definitely Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P
Grade 5 is death related to adverse event.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
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Number of Treatment-related Adverse Events for Participants Who Received Pembrolizumab
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16 Adverse events
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SECONDARY outcome
Timeframe: Date of cells until time of disease progression up to approximately 67.2 months.Population: The first combined group (n=16) is Arm 1P, the second treatment of Arm 2/1P, the initial treatment of Arm 1P/R. The second group (n=7) is Arm 1N (1/8 participants was not treated). The third group (n=12) is Arm 2 and the initial treatment of Arm 2/1P. The final group (n=2) will report the second treatment of Arm 1P/R. This enables reporting of the 37 treatments among the 32 treated participants separated by exposure to pembrolizumab/nivolumab and chemo dose. 0 participants analyzed= not treated.
PFS is defined as the time to disease progression following the start of treatment, and time to death following the start of treatment. Progression was assessed by the Response Evaluation Criteria In Solid Tumors (RECIST) v1.0 and is defined as at least a 20% increase in the sum of the longest diameter (LD) 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 |
Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=16 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=7 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=12 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=2 Participants
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 5 is death related to adverse event.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Possibly Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 3 - Probably Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 3 - Definitely Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Possibly Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Probably Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Definitely Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P
Grade 5 is death related to adverse event.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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Progression-free Survival (PFS)
Initial Treatment
|
3.1 Months
Interval 1.3 to 14.6
|
7.9 Months
Interval 2.0 to
Upper end was not reached because some participants had not progressed when taken off study.
|
2.1 Months
Interval 0.9 to 12.8
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Progression-free Survival (PFS)
Retreat
|
1.6 Months
Interval 0.1 to 5.3
|
—
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—
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32.5 Months
Interval 2.3 to
Upper end was not reached because one participant had not progressed.
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SECONDARY outcome
Timeframe: Date of cells until time to death, up until 90.1 months.Population: As pre-specified by the protocol, participants will be reported by the initial treatment arm: Arm 1N (n=7; 1/8 participants were not treated), Arm 1P (n=13), Arm 2 (n=12).
Overall survival is defined as the time from treatment start date until date of death, or date last known alive.
Outcome measures
| Measure |
Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=13 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=7 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=12 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 5 is death related to adverse event.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Possibly Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 3 - Probably Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 3 - Definitely Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Possibly Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Probably Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Definitely Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P
Grade 5 is death related to adverse event.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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Overall Survival
|
14.3 Months
Interval 2.3 to
Insufficient number of participants with events.
|
NA Months
Interval 18.7 to
Insufficient number of participants with events.
|
15.1 Months
Interval 5.4 to
Insufficient number of participants with events.
|
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—
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—
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—
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—
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SECONDARY outcome
Timeframe: An average of 25.6 months.Population: 1/8 participants were not treated in Arm 1N.
Overall survival is defined as the time from treatment start date until date of death, or date last known alive.
Outcome measures
| Measure |
Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=32 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 5 is death related to adverse event.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Possibly Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 3 - Probably Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
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Grade 3 - Definitely Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
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Grade 4 - Possibly Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
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Grade 4 - Probably Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
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Grade 4 - Definitely Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
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Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P
Grade 5 is death related to adverse event.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
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Overall Survival
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17.5 Months
Interval 2.3 to
Not applicable because some participants remain alive.
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SECONDARY outcome
Timeframe: Time to progression and time to death, approximately up to 67.2 months.Population: 1/8 participants were not treated in Arm 1N.
PFS is defined as the time to disease progression following the start of treatment, and time to death following the start of treatment. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 and is defined as at least a 20% increase in the sum of the longest diameter (LD) 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 |
Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=32 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
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Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
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Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
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Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
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Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
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Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
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Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 5 is death related to adverse event.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
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Grade 3 - Possibly Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
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Grade 3 - Probably Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
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Grade 3 - Definitely Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
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Grade 4 - Possibly Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
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Grade 4 - Probably Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
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Grade 4 - Definitely Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
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Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P
Grade 5 is death related to adverse event.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
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Overall Progression Free Survival (PFS)
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3 Months
Interval 0.9 to
Not applicable because some patients remain alive.
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OTHER_PRE_SPECIFIED outcome
Timeframe: Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.Population: 1/8 participants were not treated on Arm 1N.
Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for 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
| Measure |
Grade 3 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=7 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
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Grade 3 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=11 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
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Grade 3 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=3 Participants
Grade 3 is severe.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
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Grade 4 - Possibly Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=9 Participants
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
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Grade 4 - Probably Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
n=2 Participants
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
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Grade 4 - Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 4 is life-threatening.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
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Grade 5 - Possibly, Probably and/or Definitely Related Arm 1N, Arm 1P, Arm 2/1P, Arm 1/1P
Grade 5 is death related to adverse event.
Cohort 1: 01 - Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Grade 3 - Possibly Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 3 - Probably Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 3 - Definitely Related Arm 2, Arm 2/1P
Grade 3 is severe.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Possibly Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Probably Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 4 - Definitely Related Arm 2, Arm 2/1P
Grade 4 is life-threatening.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
Grade 5 - Possibly, Probably and/or Definitely Related Arm 2, Arm 2/1P
Grade 5 is death related to adverse event.
Cohort 1: 01 -\> 01R - Standard Chemo Prep Regimen + Retreat. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen. 01R: Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo (Retreat).
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TI) Cells + possible retreatment with standard preparative regimen + Young TIL Cells +pembrolizumab Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) or 30 mg/kg/day X 2 days IV. Days -5 to -3 (low-dose arm-CLOSED): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes.
Young TIL: Day 0: Cells will be infused intravenously (IV) Pembrolizumab: 2 mg/kg intravenous (IV) on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
|
7 Participants
|
9 Participants
|
3 Participants
|
9 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Serious events: 3 serious events
Other events: 7 other events
Deaths: 2 deaths
Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Serious events: 6 serious events
Other events: 9 other events
Deaths: 9 deaths
Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Serious events: 1 serious events
Other events: 3 other events
Deaths: 2 deaths
Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Serious events: 2 serious events
Other events: 9 other events
Deaths: 8 deaths
Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
Serious events: 1 serious events
Other events: 2 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
n=7 participants at risk
Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen in participants without prior treatment pembrolizumab or nivolumab Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
n=11 participants at risk
Standard Chemo Prep Regimen Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen in participants previously treated with pembrolizumab or nivolumab.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
n=3 participants at risk
Decreased Chemo Prep Regimen+Retreat. Young TIL+High Dose Interleukin-2, Decreased Chemo Preparative Regimen. Young TIL+High Dose Interleukin-2, Standard Chemo (Retreat). Lower dose preparative regimen + Young TIL Cells. Aldesleukin: 720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days. Cyclophosphamide: Days -5 to -3 (low-dose arm): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused IV. Retreatment: Standard Chemo Prep Regimen. Aldesleukin: 720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days. Cyclophosphamide: 60 mg/kg/day X 2 days IV. Young TIL: Day 0: Cells will be infused IV.
|
Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
n=9 participants at risk
Decreased Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2 Lower Dose preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days Cyclophosphamide: Days -5 to -3 (low-dose arm): Cyclophosphamide 30 mg/kg IV over 60 minutes for 2 days.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
n=2 participants at risk
Standard Chemo Prep Regimen(SCPR)+Retreat. Young TIL+High Dose(HD) Interleukin-2, SCPR. Young TIL+HD Interleukin-2, SC(Retreat). SCPR+Young TIL Cells retreatment with SCPR+Young TIL Cells+pembrolizumab. Aldesleukin:720,000 IU/kgIV every eight hours (+/-1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine:25 mg/m\^2/day intravenous piggy-back(IVPB) daily for 5 days. Cyclophosphamide:60 mg/kg/day X 2 days IV. Young TIL:Day 0: Cells will be infused IV. Retreatment with standard preparative regimen+Young TIL Cells+pembrolizumab. Aldesleukin:720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine:25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days. Cyclophosphamide:60 mg/kg/day X 2 days IV. Young TIL: Day 0:Cells will be infused IV. Pembrolizumab:2 mg/kg IV on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
|---|---|---|---|---|---|
|
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Investigations
AST, SGOT(serum glutamic oxaloacetic transaminase)
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
9.1%
1/11 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Psychiatric disorders
Confusion
|
14.3%
1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
18.2%
2/11 • Number of events 2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Investigations
Hemoglobin
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
18.2%
2/11 • Number of events 2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Vascular disorders
Hypotension
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
9.1%
1/11 • Number of events 2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
9.1%
1/11 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Infections and infestations
Infection
|
42.9%
3/7 • Number of events 3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
9.1%
1/11 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Cardiac disorders
Left ventricular systolic dysfunction
|
14.3%
1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Investigations
Lymphopenia
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
9.1%
1/11 • Number of events 2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Investigations
Neutrophils/granulocytes (ANC/AGC)
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
11.1%
1/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Investigations
Platelets
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
9.1%
1/11 • Number of events 2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Investigations
Weight loss
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
Other adverse events
| Measure |
Arm 1N -Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
n=7 participants at risk
Standard Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen in participants without prior treatment pembrolizumab or nivolumab Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Arm 1P - Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
n=11 participants at risk
Standard Chemo Prep Regimen Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2, Standard Chemo Preparative Regimen in participants previously treated with pembrolizumab or nivolumab.
Standard preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days Cyclophosphamide: 60 mg/kg/day X 2 days intravenous (IV) Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Arm 2/Foll By Arm 1P-Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
n=3 participants at risk
Decreased Chemo Prep Regimen+Retreat. Young TIL+High Dose Interleukin-2, Decreased Chemo Preparative Regimen. Young TIL+High Dose Interleukin-2, Standard Chemo (Retreat). Lower dose preparative regimen + Young TIL Cells. Aldesleukin: 720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days. Cyclophosphamide: Days -5 to -3 (low-dose arm): Cyclophosphamide 300 mg/m\^2 IV over 60 minutes. Young TIL: Day 0: Cells will be infused IV. Retreatment: Standard Chemo Prep Regimen. Aldesleukin: 720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine: 25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days. Cyclophosphamide: 60 mg/kg/day X 2 days IV. Young TIL: Day 0: Cells will be infused IV.
|
Arm 2- Low Dose Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
n=9 participants at risk
Decreased Chemo Prep Regimen. Young Tumor Infiltrating Lymphocytes (TIL) Plus High Dose Interleukin-2 Lower Dose preparative regimen + Young Tumor Infiltrating Lymphocytes (TIL) Cells Aldesleukin: 720,000 IU/kg intravenous (IV) every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses).
Fludarabine: 30 mg/kg/day intravenous piggy-back (IVPB) daily for 3 days Cyclophosphamide: Days -5 to -3 (low-dose arm): Cyclophosphamide 30 mg/kg IV over 60 minutes for 2 days.
Young TIL: Day 0: Cells will be infused intravenously (IV)
|
Arm 1P/Foll By Arm-1P/R-Standard Chemotherapy Preparative Regimen + TIL + 720,000 IU/kg Aldesleukin
n=2 participants at risk
Standard Chemo Prep Regimen(SCPR)+Retreat. Young TIL+High Dose(HD) Interleukin-2, SCPR. Young TIL+HD Interleukin-2, SC(Retreat). SCPR+Young TIL Cells retreatment with SCPR+Young TIL Cells+pembrolizumab. Aldesleukin:720,000 IU/kgIV every eight hours (+/-1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine:25 mg/m\^2/day intravenous piggy-back(IVPB) daily for 5 days. Cyclophosphamide:60 mg/kg/day X 2 days IV. Young TIL:Day 0: Cells will be infused IV. Retreatment with standard preparative regimen+Young TIL Cells+pembrolizumab. Aldesleukin:720,000 IU/kg IV every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 4 days (maximum 12 doses). Fludarabine:25 mg/m\^2/day intravenous piggy-back (IVPB) daily for 5 days. Cyclophosphamide:60 mg/kg/day X 2 days IV. Young TIL: Day 0:Cells will be infused IV. Pembrolizumab:2 mg/kg IV on Days -2, 21 (+/- 2 days), 42 (+/- 2 days), and 63 (+/- 2 days).
|
|---|---|---|---|---|---|
|
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)
|
14.3%
1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
9.1%
1/11 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Investigations
AST, SGOT(serum glutamic oxaloacetic transaminase)
|
14.3%
1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)
|
14.3%
1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
9.1%
1/11 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Investigations
Bilirubin (hyperbilirubinemia)
|
14.3%
1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
9.1%
1/11 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Psychiatric disorders
Confusion
|
14.3%
1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
9.1%
1/11 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Investigations
Creatinine
|
42.9%
3/7 • Number of events 3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
18.2%
2/11 • Number of events 2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
9.1%
1/11 • Number of events 2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
14.3%
1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
18.2%
2/11 • Number of events 2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
66.7%
2/3 • Number of events 3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
44.4%
4/9 • Number of events 4 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Investigations
Hemoglobin
|
28.6%
2/7 • Number of events 2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
36.4%
4/11 • Number of events 6 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
100.0%
3/3 • Number of events 5 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Reproductive system and breast disorders
Hemorrhage, GU::Vagina
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Skin and subcutaneous tissue disorders
Hypopigmentation
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Vascular disorders
Hypotension
|
14.3%
1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
18.2%
2/11 • Number of events 2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
66.7%
2/3 • Number of events 3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
44.4%
4/9 • Number of events 4 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
14.3%
1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
9.1%
1/11 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Infections and infestations
Infection
|
14.3%
1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Investigations
Leukocytes (total WBC)
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
9.1%
1/11 • Number of events 5 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Investigations
Lymphopenia
|
57.1%
4/7 • Number of events 4 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
63.6%
7/11 • Number of events 10 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
66.7%
2/3 • Number of events 4 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
88.9%
8/9 • Number of events 8 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
100.0%
2/2 • Number of events 4 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Psychiatric disorders
Mood alteration::Agitation
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
9.1%
1/11 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Investigations
Neutrophils/granulocytes (ANC/AGC)
|
57.1%
4/7 • Number of events 4 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
63.6%
7/11 • Number of events 7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
66.7%
2/3 • Number of events 3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
44.4%
4/9 • Number of events 4 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
100.0%
2/2 • Number of events 5 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Investigations
PTT (Partial Thromboplastin Time)
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
18.2%
2/11 • Number of events 2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
66.7%
2/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Nervous system disorders
Pain::Head/headache
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pain::Tumor pain
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Metabolism and nutrition disorders
Phosphate, serum-low (hypophosphatemia)
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
9.1%
1/11 • Number of events 3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Investigations
Platelets
|
57.1%
4/7 • Number of events 4 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
54.5%
6/11 • Number of events 7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
66.7%
2/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
100.0%
2/2 • Number of events 5 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Skin and subcutaneous tissue disorders
Pruritus/itching
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
9.1%
1/11 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Psychiatric disorders
Psychosis (hallucinations/delusions)
|
28.6%
2/7 • Number of events 2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
50.0%
1/2 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
9.1%
1/11 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Renal and urinary disorders
Renal failure
|
14.3%
1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Renal and urinary disorders
Renal/Genitourinary - Other (oliguria)
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
General disorders
Rigors/chills
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Cardiac disorders
Supraventricular and nodal arrhythmia::Sinus tachycardia
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Vascular disorders
Thrombosis/thrombus/embolism
|
14.3%
1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Endocrine disorders
Thyroid function, low (hypothyroidism)
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Metabolism and nutrition disorders
Uric acid, serum-high (hyperuricemia)
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Eye disorders
Uveitis
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
9.1%
1/11 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Eye disorders
Vision-blurred vision
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/11 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
9.1%
1/11 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
|
Investigations
Leukocytes (total white blood cell (WBC)
|
0.00%
0/7 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
9.1%
1/11 • Number of events 5 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
0.00%
0/2 • Date treatment consent signed to date off study, approximately 102 months and 9 days, 92 months and 19 days, 86 months and 9 days, 99 months and 16 days, and 86 months and 26 days for each group respectively.
1/8 participants were not treated in Arm 1N.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place