Trial Outcomes & Findings for Lymphodepletion Plus Adoptive Cell Therapy With High Dose IL-2 in Adolescent and Young Adult Patients With Soft Tissue Sarcoma (NCT NCT04052334)
NCT ID: NCT04052334
Last Updated: 2025-08-21
Results Overview
Participants able to safely tolerate preparatory lymphodepletion, infusion of tumor-infiltrating lymphocytes (TIL) and subsequent IL-2, as measured by adverse events and serious adverse events.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
9 participants
Primary outcome timeframe
Baseline to 12 months
Results posted on
2025-08-21
Participant Flow
Participant milestones
| Measure |
Infusion of Tumor-infiltrating Lymphocyte
Participants will undergo tumor resection from which the tumor infiltrating lymphocyte (TIL) product will be generated. All participants will receive nonmyeloablative lymphodepleting chemotherapy with cyclophosphamide and fludarabine to enhance T-cell persistence and effectiveness in vivo. Cyclophosphamide will be administered at 60 mg/kg/day IV in 250 mL normal saline (NS). Fludarabine will then be infused at 25 mg/m\^2 intravenous piggyback (IVPB). All participants will receive not less than 10\^9, and up to 1x10\^12 T cells in ≥250 mL NS as an inpatient by IV.
Eight (8) to sixteen (16) hours after completing the T cell infusion, all participants will receive high-dose interleukin-2 (IL-2) on an inpatient basis at the standard dose of 600 000 IU/kg as an IV bolus over an approximate 15-minute period every 8 to 16 hours for up to 15 doses on days 1 to 5, as tolerated.
TIL: Participants will receive an infusion of TIL after tumor resection and TIL product is generated.
Interleukin-2 (IL-2): Participants will receive IL-2 600 000 IU/kg intravenously (IV) bolus (about 15 minutes) every 8 to 16 hours for up to 15 doses, beginning approximately 8 to 16 hours after T-cell infusion.
Fludarabine: Participants will receive an IV infusion of Fludarabine 25 mg/m2 for approximately 30 minutes for 5 days, prior to T-Cell infusion
Cyclophosphamide: Participants will receive Cyclophosphamide 60 mg/kg/day IV in 250 mL NS over approximately 2 hours, 7 days prior to T-Cell infusion
|
|---|---|
|
Overall Study
STARTED
|
9
|
|
Overall Study
COMPLETED
|
5
|
|
Overall Study
NOT COMPLETED
|
4
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Lymphodepletion Plus Adoptive Cell Therapy With High Dose IL-2 in Adolescent and Young Adult Patients With Soft Tissue Sarcoma
Baseline characteristics by cohort
| Measure |
Infusion of Tumor-infiltrating Lymphocyte
n=9 Participants
Participants will undergo tumor resection from which the tumor infiltrating lymphocyte (TIL) product will be generated. All participants will receive nonmyeloablative lymphodepleting chemotherapy with cyclophosphamide and fludarabine to enhance T-cell persistence and effectiveness in vivo. Cyclophosphamide will be administered at 60 mg/kg/day IV in 250 mL normal saline (NS). Fludarabine will then be infused at 25 mg/m\^2 intravenous piggyback (IVPB). All participants will receive not less than 10\^9, and up to 1x10\^12 T cells in ≥250 mL NS as an inpatient by IV.
Eight (8) to sixteen (16) hours after completing the T cell infusion, all participants will receive high-dose interleukin-2 (IL-2) on an inpatient basis at the standard dose of 600 000 IU/kg as an IV bolus over an approximate 15-minute period every 8 to 16 hours for up to 15 doses on days 1 to 5, as tolerated.
TIL: Participants will receive an infusion of TIL after tumor resection and TIL product is generated.
Interleukin-2 (IL-2): Participants will receive IL-2 600 000 IU/kg intravenously (IV) bolus (about 15 minutes) every 8 to 16 hours for up to 15 doses, beginning approximately 8 to 16 hours after T-cell infusion.
Fludarabine: Participants will receive an IV infusion of Fludarabine 25 mg/m2 for approximately 30 minutes for 5 days, prior to T-Cell infusion
Cyclophosphamide: Participants will receive Cyclophosphamide 60 mg/kg/day IV in 250 mL NS over approximately 2 hours, 7 days prior to T-Cell infusion
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
9 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
9 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to 12 monthsParticipants able to safely tolerate preparatory lymphodepletion, infusion of tumor-infiltrating lymphocytes (TIL) and subsequent IL-2, as measured by adverse events and serious adverse events.
Outcome measures
| Measure |
Infusion of Tumor-infiltrating Lymphocyte
n=9 Participants
Participants will undergo tumor resection from which the tumor infiltrating lymphocyte (TIL) product will be generated. All participants will receive nonmyeloablative lymphodepleting chemotherapy with cyclophosphamide and fludarabine to enhance T-cell persistence and effectiveness in vivo. Cyclophosphamide will be administered at 60 mg/kg/day IV in 250 mL normal saline (NS). Fludarabine will then be infused at 25 mg/m\^2 intravenous piggyback (IVPB). All participants will receive not less than 10\^9, and up to 1x10\^12 T cells in ≥250 mL NS as an inpatient by IV.
Eight (8) to sixteen (16) hours after completing the T cell infusion, all participants will receive high-dose interleukin-2 (IL-2) on an inpatient basis at the standard dose of 600 000 IU/kg as an IV bolus over an approximate 15-minute period every 8 to 16 hours for up to 15 doses on days 1 to 5, as tolerated.
TIL: Participants will receive an infusion of TIL after tumor resection and TIL product is generated.
Interleukin-2 (IL-2): Participants will receive IL-2 600 000 IU/kg intravenously (IV) bolus (about 15 minutes) every 8 to 16 hours for up to 15 doses, beginning approximately 8 to 16 hours after T-cell infusion.
Fludarabine: Participants will receive an IV infusion of Fludarabine 25 mg/m2 for approximately 30 minutes for 5 days, prior to T-Cell infusion
Cyclophosphamide: Participants will receive Cyclophosphamide 60 mg/kg/day IV in 250 mL NS over approximately 2 hours, 7 days prior to T-Cell infusion
|
|---|---|
|
Number of Participants Who Experienced Serious Adverse Events and Adverse Events
No adverse events noted
|
5 Participants
|
|
Number of Participants Who Experienced Serious Adverse Events and Adverse Events
Adverse event
|
4 Participants
|
SECONDARY outcome
Timeframe: At 12 weeksNumber of participants with objective response (Complete Response (CR) + Progressive Response (PR)) rate at 12 weeks following TIL infusion, as measured by RECIST v1.1
Outcome measures
| Measure |
Infusion of Tumor-infiltrating Lymphocyte
n=9 Participants
Participants will undergo tumor resection from which the tumor infiltrating lymphocyte (TIL) product will be generated. All participants will receive nonmyeloablative lymphodepleting chemotherapy with cyclophosphamide and fludarabine to enhance T-cell persistence and effectiveness in vivo. Cyclophosphamide will be administered at 60 mg/kg/day IV in 250 mL normal saline (NS). Fludarabine will then be infused at 25 mg/m\^2 intravenous piggyback (IVPB). All participants will receive not less than 10\^9, and up to 1x10\^12 T cells in ≥250 mL NS as an inpatient by IV.
Eight (8) to sixteen (16) hours after completing the T cell infusion, all participants will receive high-dose interleukin-2 (IL-2) on an inpatient basis at the standard dose of 600 000 IU/kg as an IV bolus over an approximate 15-minute period every 8 to 16 hours for up to 15 doses on days 1 to 5, as tolerated.
TIL: Participants will receive an infusion of TIL after tumor resection and TIL product is generated.
Interleukin-2 (IL-2): Participants will receive IL-2 600 000 IU/kg intravenously (IV) bolus (about 15 minutes) every 8 to 16 hours for up to 15 doses, beginning approximately 8 to 16 hours after T-cell infusion.
Fludarabine: Participants will receive an IV infusion of Fludarabine 25 mg/m2 for approximately 30 minutes for 5 days, prior to T-Cell infusion
Cyclophosphamide: Participants will receive Cyclophosphamide 60 mg/kg/day IV in 250 mL NS over approximately 2 hours, 7 days prior to T-Cell infusion
|
|---|---|
|
Number of Participants With Objective Antitumor Response
|
0 Participants
|
SECONDARY outcome
Timeframe: At 6 weeksNumber of participants with persistence of TIL infusion product at 6 weeks following treatment, as measured by T-cell receptor repertoire comparison between the infusion product and circulating Peripheral blood mononuclear cell (PBMC).
Outcome measures
| Measure |
Infusion of Tumor-infiltrating Lymphocyte
n=5 Participants
Participants will undergo tumor resection from which the tumor infiltrating lymphocyte (TIL) product will be generated. All participants will receive nonmyeloablative lymphodepleting chemotherapy with cyclophosphamide and fludarabine to enhance T-cell persistence and effectiveness in vivo. Cyclophosphamide will be administered at 60 mg/kg/day IV in 250 mL normal saline (NS). Fludarabine will then be infused at 25 mg/m\^2 intravenous piggyback (IVPB). All participants will receive not less than 10\^9, and up to 1x10\^12 T cells in ≥250 mL NS as an inpatient by IV.
Eight (8) to sixteen (16) hours after completing the T cell infusion, all participants will receive high-dose interleukin-2 (IL-2) on an inpatient basis at the standard dose of 600 000 IU/kg as an IV bolus over an approximate 15-minute period every 8 to 16 hours for up to 15 doses on days 1 to 5, as tolerated.
TIL: Participants will receive an infusion of TIL after tumor resection and TIL product is generated.
Interleukin-2 (IL-2): Participants will receive IL-2 600 000 IU/kg intravenously (IV) bolus (about 15 minutes) every 8 to 16 hours for up to 15 doses, beginning approximately 8 to 16 hours after T-cell infusion.
Fludarabine: Participants will receive an IV infusion of Fludarabine 25 mg/m2 for approximately 30 minutes for 5 days, prior to T-Cell infusion
Cyclophosphamide: Participants will receive Cyclophosphamide 60 mg/kg/day IV in 250 mL NS over approximately 2 hours, 7 days prior to T-Cell infusion
|
|---|---|
|
Number of Participants With Circulating Tumor-infiltrating Lymphocytes (TIL) Product at 6 Weeks
|
5 Participants
|
Adverse Events
Infusion of Tumor-infiltrating Lymphocyte
Serious events: 3 serious events
Other events: 9 other events
Deaths: 4 deaths
Serious adverse events
| Measure |
Infusion of Tumor-infiltrating Lymphocyte
n=9 participants at risk
Participants will undergo tumor resection from which the tumor infiltrating lymphocyte (TIL) product will be generated. All participants will receive nonmyeloablative lymphodepleting chemotherapy with cyclophosphamide and fludarabine to enhance T-cell persistence and effectiveness in vivo. Cyclophosphamide will be administered at 60 mg/kg/day IV in 250 mL normal saline (NS). Fludarabine will then be infused at 25 mg/m\^2 intravenous piggyback (IVPB). All participants will receive not less than 10\^9, and up to 1x10\^12 T cells in ≥250 mL NS as an inpatient by IV.
Eight (8) to sixteen (16) hours after completing the T cell infusion, all participants will receive high-dose interleukin-2 (IL-2) on an inpatient basis at the standard dose of 600 000 IU/kg as an IV bolus over an approximate 15-minute period every 8 to 16 hours for up to 15 doses on days 1 to 5, as tolerated.
TIL: Participants will receive an infusion of TIL after tumor resection and TIL product is generated.
Interleukin-2 (IL-2): Participants will receive IL-2 600 000 IU/kg intravenously (IV) bolus (about 15 minutes) every 8 to 16 hours for up to 15 doses, beginning approximately 8 to 16 hours after T-cell infusion.
Fludarabine: Participants will receive an IV infusion of Fludarabine 25 mg/m2 for approximately 30 minutes for 5 days, prior to T-Cell infusion
Cyclophosphamide: Participants will receive Cyclophosphamide 60 mg/kg/day IV in 250 mL NS over approximately 2 hours, 7 days prior to T-Cell infusion
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, specify
|
11.1%
1/9 • Number of events 1 • 1 year
AE's assessed at follow up visits.
|
|
Cardiac disorders
Sinus tachycardia
|
22.2%
2/9 • Number of events 2 • 1 year
AE's assessed at follow up visits.
|
|
Vascular disorders
Hypotension
|
22.2%
2/9 • Number of events 3 • 1 year
AE's assessed at follow up visits.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
11.1%
1/9 • Number of events 1 • 1 year
AE's assessed at follow up visits.
|
|
Blood and lymphatic system disorders
Bone marrow hypocellular
|
11.1%
1/9 • Number of events 1 • 1 year
AE's assessed at follow up visits.
|
|
General disorders
Disease progression
|
11.1%
1/9 • Number of events 1 • 1 year
AE's assessed at follow up visits.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
11.1%
1/9 • Number of events 1 • 1 year
AE's assessed at follow up visits.
|
|
General disorders
General disorders and administration site conditions - Other, specify - Residual COVID-19
|
11.1%
1/9 • Number of events 1 • 1 year
AE's assessed at follow up visits.
|
Other adverse events
| Measure |
Infusion of Tumor-infiltrating Lymphocyte
n=9 participants at risk
Participants will undergo tumor resection from which the tumor infiltrating lymphocyte (TIL) product will be generated. All participants will receive nonmyeloablative lymphodepleting chemotherapy with cyclophosphamide and fludarabine to enhance T-cell persistence and effectiveness in vivo. Cyclophosphamide will be administered at 60 mg/kg/day IV in 250 mL normal saline (NS). Fludarabine will then be infused at 25 mg/m\^2 intravenous piggyback (IVPB). All participants will receive not less than 10\^9, and up to 1x10\^12 T cells in ≥250 mL NS as an inpatient by IV.
Eight (8) to sixteen (16) hours after completing the T cell infusion, all participants will receive high-dose interleukin-2 (IL-2) on an inpatient basis at the standard dose of 600 000 IU/kg as an IV bolus over an approximate 15-minute period every 8 to 16 hours for up to 15 doses on days 1 to 5, as tolerated.
TIL: Participants will receive an infusion of TIL after tumor resection and TIL product is generated.
Interleukin-2 (IL-2): Participants will receive IL-2 600 000 IU/kg intravenously (IV) bolus (about 15 minutes) every 8 to 16 hours for up to 15 doses, beginning approximately 8 to 16 hours after T-cell infusion.
Fludarabine: Participants will receive an IV infusion of Fludarabine 25 mg/m2 for approximately 30 minutes for 5 days, prior to T-Cell infusion
Cyclophosphamide: Participants will receive Cyclophosphamide 60 mg/kg/day IV in 250 mL NS over approximately 2 hours, 7 days prior to T-Cell infusion
|
|---|---|
|
Blood and lymphatic system disorders
Bone marrow hypocellular
|
11.1%
1/9 • Number of events 1 • 1 year
AE's assessed at follow up visits.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
11.1%
1/9 • Number of events 1 • 1 year
AE's assessed at follow up visits.
|
|
Cardiac disorders
Sinus tachycardia
|
22.2%
2/9 • Number of events 2 • 1 year
AE's assessed at follow up visits.
|
|
General disorders
Fever
|
22.2%
2/9 • Number of events 2 • 1 year
AE's assessed at follow up visits.
|
|
General disorders
Chills
|
11.1%
1/9 • Number of events 1 • 1 year
AE's assessed at follow up visits.
|
|
Infections and infestations
Infections and infestations - Other, specify
|
11.1%
1/9 • Number of events 2 • 1 year
AE's assessed at follow up visits.
|
|
Infections and infestations
Skin infection
|
11.1%
1/9 • Number of events 1 • 1 year
AE's assessed at follow up visits.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
22.2%
2/9 • Number of events 4 • 1 year
AE's assessed at follow up visits.
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal hemorrhage
|
11.1%
1/9 • Number of events 1 • 1 year
AE's assessed at follow up visits.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, specify
|
11.1%
1/9 • Number of events 2 • 1 year
AE's assessed at follow up visits.
|
|
Vascular disorders
Hypotension
|
22.2%
2/9 • Number of events 3 • 1 year
AE's assessed at follow up visits.
|
|
Nervous system disorders
Encephalopathy
|
11.1%
1/9 • Number of events 1 • 1 year
AE's assessed at follow up visits.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place