Trial Outcomes & Findings for Cell Therapy for Metastatic Melanoma Using CD8 Enriched Tumor Infiltrating Lymphocytes (NCT NCT01236573)
NCT ID: NCT01236573
Last Updated: 2015-11-26
Results Overview
The MTD was determined by evaluating dose limiting toxicities (DLT) of participants that received increasing doses of intravenous infusion of IL-12 gene transduced tumor infiltrating lymphocytes (TIL) (i.e., 1x10\^6, 3x10\^6, 3x10\^7, 1x10\^7, 3x10\^7, 1x10\^8, 3x10\^8, 1x10\^9, and 3x10\^9) in cohorts 1-10. Maximum tolerated cell dose is the highest dose at which \</= 1 of 6 patients experienced a DLT (i.e. grade 2 or greater allergic reaction)).
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
34 participants
Primary outcome timeframe
4 years
Results posted on
2015-11-26
Participant Flow
Participant milestones
| Measure |
Group 1 - CD8 + TIL Expressing IL-12 1x10^6 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Phase 1-Dose Escalation-Cohorts 1-4
STARTED
|
1
|
1
|
6
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1-Dose Escalation-Cohorts 1-4
COMPLETED
|
1
|
1
|
6
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1-Dose Escalation-Cohorts 1-4
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1-Dose Escalation-Cohorts 5-10
STARTED
|
0
|
0
|
0
|
0
|
1
|
4
|
3
|
3
|
4
|
4
|
0
|
|
Phase 1-Dose Escalation-Cohorts 5-10
COMPLETED
|
0
|
0
|
0
|
0
|
1
|
4
|
2
|
3
|
2
|
3
|
0
|
|
Phase 1-Dose Escalation-Cohorts 5-10
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
2
|
1
|
0
|
|
Phase 2- MTD/Anti-IL-12 Cells-Cohort 11
STARTED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
6
|
|
Phase 2- MTD/Anti-IL-12 Cells-Cohort 11
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
5
|
|
Phase 2- MTD/Anti-IL-12 Cells-Cohort 11
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Group 1 - CD8 + TIL Expressing IL-12 1x10^6 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Phase 1-Dose Escalation-Cohorts 5-10
Death during treatment
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
1
|
1
|
0
|
|
Phase 1-Dose Escalation-Cohorts 5-10
Not treated
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Phase 2- MTD/Anti-IL-12 Cells-Cohort 11
Did not receive cells
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Cell Therapy for Metastatic Melanoma Using CD8 Enriched Tumor Infiltrating Lymphocytes
Baseline characteristics by cohort
| Measure |
Group 1 - CD8 + TIL Expressing IL-12 1x10^6 (Phase 1)
n=1 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)
n=1 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)
n=6 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)
n=1 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)
n=1 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)
n=4 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)
n=3 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)
n=3 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)
n=4 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)
n=4 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
n=6 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Total
n=34 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=40 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=62 Participants
|
0 Participants
n=95 Participants
|
0 Participants
n=129 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
4 Participants
n=10 Participants
|
3 Participants
n=115 Participants
|
3 Participants
n=40 Participants
|
3 Participants
n=8 Participants
|
3 Participants
n=62 Participants
|
5 Participants
n=95 Participants
|
31 Participants
n=129 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=40 Participants
|
1 Participants
n=8 Participants
|
1 Participants
n=62 Participants
|
1 Participants
n=95 Participants
|
3 Participants
n=129 Participants
|
|
Age, Continuous
|
56.0 years
STANDARD_DEVIATION 0 • n=93 Participants
|
50.0 years
STANDARD_DEVIATION 0 • n=4 Participants
|
39.0 years
STANDARD_DEVIATION 11.5 • n=27 Participants
|
48.0 years
STANDARD_DEVIATION 0 • n=483 Participants
|
60.0 years
STANDARD_DEVIATION 0 • n=36 Participants
|
57.3 years
STANDARD_DEVIATION 10.9 • n=10 Participants
|
49.0 years
STANDARD_DEVIATION 14.5 • n=115 Participants
|
56.0 years
STANDARD_DEVIATION 9.6 • n=40 Participants
|
53.5 years
STANDARD_DEVIATION 16.2 • n=8 Participants
|
55.8 years
STANDARD_DEVIATION 12.2 • n=62 Participants
|
49.3 years
STANDARD_DEVIATION 16.5 • n=95 Participants
|
50.7 years
STANDARD_DEVIATION 13.0 • n=129 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
1 Participants
n=10 Participants
|
2 Participants
n=115 Participants
|
1 Participants
n=40 Participants
|
1 Participants
n=8 Participants
|
2 Participants
n=62 Participants
|
0 Participants
n=95 Participants
|
9 Participants
n=129 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
3 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
2 Participants
n=40 Participants
|
3 Participants
n=8 Participants
|
2 Participants
n=62 Participants
|
6 Participants
n=95 Participants
|
25 Participants
n=129 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
1 Participants
n=40 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=62 Participants
|
0 Participants
n=95 Participants
|
2 Participants
n=129 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
4 Participants
n=10 Participants
|
3 Participants
n=115 Participants
|
2 Participants
n=40 Participants
|
4 Participants
n=8 Participants
|
3 Participants
n=62 Participants
|
6 Participants
n=95 Participants
|
32 Participants
n=129 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=40 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=62 Participants
|
0 Participants
n=95 Participants
|
0 Participants
n=129 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=40 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=62 Participants
|
0 Participants
n=95 Participants
|
0 Participants
n=129 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=40 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=62 Participants
|
0 Participants
n=95 Participants
|
0 Participants
n=129 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=40 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=62 Participants
|
0 Participants
n=95 Participants
|
0 Participants
n=129 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=40 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=62 Participants
|
0 Participants
n=95 Participants
|
0 Participants
n=129 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
4 Participants
n=10 Participants
|
3 Participants
n=115 Participants
|
3 Participants
n=40 Participants
|
4 Participants
n=8 Participants
|
3 Participants
n=62 Participants
|
6 Participants
n=95 Participants
|
33 Participants
n=129 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=40 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=62 Participants
|
0 Participants
n=95 Participants
|
0 Participants
n=129 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=40 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=62 Participants
|
0 Participants
n=95 Participants
|
1 Participants
n=129 Participants
|
|
Region of Enrollment
United States
|
1 participants
n=93 Participants
|
1 participants
n=4 Participants
|
6 participants
n=27 Participants
|
1 participants
n=483 Participants
|
1 participants
n=36 Participants
|
4 participants
n=10 Participants
|
3 participants
n=115 Participants
|
3 participants
n=40 Participants
|
4 participants
n=8 Participants
|
4 participants
n=62 Participants
|
6 participants
n=95 Participants
|
34 participants
n=129 Participants
|
PRIMARY outcome
Timeframe: 4 yearsThe MTD was determined by evaluating dose limiting toxicities (DLT) of participants that received increasing doses of intravenous infusion of IL-12 gene transduced tumor infiltrating lymphocytes (TIL) (i.e., 1x10\^6, 3x10\^6, 3x10\^7, 1x10\^7, 3x10\^7, 1x10\^8, 3x10\^8, 1x10\^9, and 3x10\^9) in cohorts 1-10. Maximum tolerated cell dose is the highest dose at which \</= 1 of 6 patients experienced a DLT (i.e. grade 2 or greater allergic reaction)).
Outcome measures
| Measure |
All Phase I Participants
n=28 Participants
All phase I participants who received at least one dose intravenously of CD8 + TIL expressing IL-12 in Groups 1-4, and Bulk TIL expressing IL-12 in Groups 5-10 (i.e., CD8 + TIL expressing IL-12 1x10\^6, CD8 + TIL expressing IL-12 3x10\^6, CD8 + TIL expressing IL-12 3x10\^7, CD8 + TIL expressing IL-12 3x10\^7, Bulk TIL expressing IL-12 1x10\^7, Bulk TIL expressing IL-12 3x10\^7, Bulk TIL expressing IL-12 1x10\^8, Bulk TIL expressing IL-12 3x10\^8, Bulk TIL expressing IL-12 1x10\^9, and Bulk TIL expressing IL-12 3x10\^9) respectively.
|
Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Maximum Tolerated Dose (MTD)
|
1,000,000,000 Cells
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 4 yearsResponse was determined 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 um 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 lesions.
Outcome measures
| Measure |
All Phase I Participants
n=1 Participants
All phase I participants who received at least one dose intravenously of CD8 + TIL expressing IL-12 in Groups 1-4, and Bulk TIL expressing IL-12 in Groups 5-10 (i.e., CD8 + TIL expressing IL-12 1x10\^6, CD8 + TIL expressing IL-12 3x10\^6, CD8 + TIL expressing IL-12 3x10\^7, CD8 + TIL expressing IL-12 3x10\^7, Bulk TIL expressing IL-12 1x10\^7, Bulk TIL expressing IL-12 3x10\^7, Bulk TIL expressing IL-12 1x10\^8, Bulk TIL expressing IL-12 3x10\^8, Bulk TIL expressing IL-12 1x10\^9, and Bulk TIL expressing IL-12 3x10\^9) respectively.
|
Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)
n=1 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)
n=6 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)
n=1 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)
n=1 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)
n=4 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)
n=3 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)
n=3 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)
n=4 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)
n=4 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
n=6 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Response (Complete Response (CR) + Partial Response (PR)) to Therapy
Complete Response (CR)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
|
Response (Complete Response (CR) + Partial Response (PR)) to Therapy
Partial Response (PR)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
3 participants
|
1 participants
|
|
Response (Complete Response (CR) + Partial Response (PR)) to Therapy
Progressive Disease (PD)
|
1 participants
|
1 participants
|
6 participants
|
0 participants
|
1 participants
|
4 participants
|
2 participants
|
2 participants
|
2 participants
|
0 participants
|
3 participants
|
|
Response (Complete Response (CR) + Partial Response (PR)) to Therapy
Not Assessed (NA)
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
1 participants
|
1 participants
|
1 participants
|
0 participants
|
1 participants
|
|
Response (Complete Response (CR) + Partial Response (PR)) to Therapy
Not Evaluable (NE)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
SECONDARY outcome
Timeframe: 49 months and 20 daysHere is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Outcome measures
| Measure |
All Phase I Participants
n=1 Participants
All phase I participants who received at least one dose intravenously of CD8 + TIL expressing IL-12 in Groups 1-4, and Bulk TIL expressing IL-12 in Groups 5-10 (i.e., CD8 + TIL expressing IL-12 1x10\^6, CD8 + TIL expressing IL-12 3x10\^6, CD8 + TIL expressing IL-12 3x10\^7, CD8 + TIL expressing IL-12 3x10\^7, Bulk TIL expressing IL-12 1x10\^7, Bulk TIL expressing IL-12 3x10\^7, Bulk TIL expressing IL-12 1x10\^8, Bulk TIL expressing IL-12 3x10\^8, Bulk TIL expressing IL-12 1x10\^9, and Bulk TIL expressing IL-12 3x10\^9) respectively.
|
Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)
n=1 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)
n=6 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)
n=1 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)
n=1 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)
n=4 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)
n=3 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)
n=3 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)
n=4 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)
n=4 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
n=6 Participants
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Adverse Events
|
1 participants
|
1 participants
|
6 participants
|
1 participants
|
1 participants
|
4 participants
|
3 participants
|
3 participants
|
4 participants
|
4 participants
|
6 participants
|
Adverse Events
Group 1 - CD8 + TIL Expressing IL-12 1x10^6 (Phase 1)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Group 1 - CD8 + TIL Expressing IL-12 1x10^6 (Phase 1)
n=1 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)
n=1 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)
n=6 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)
n=1 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)
n=1 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)
n=4 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)
n=3 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)
n=3 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)
n=4 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)
n=4 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
n=6 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Platelets
|
0.00%
0/1
|
0.00%
0/1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0x10e9/L)
|
0.00%
0/1
|
0.00%
0/1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Hemoglobin
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Vascular disorders
Thrombosis/thrombus/embolism
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Bilirubin (Hyperbilirubinemia)
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Creatinine
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
|
Vascular disorders
Thrombotic microangiopathy
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis/pulmonary infiltrates
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase)
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
16.7%
1/6 • Number of events 1
|
|
Metabolism and nutrition disorders
AST, SGOT (serum glutamic oxaloacetic transaminase)
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
33.3%
2/6 • Number of events 2
|
Other adverse events
| Measure |
Group 1 - CD8 + TIL Expressing IL-12 1x10^6 (Phase 1)
n=1 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)
n=1 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)
n=6 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)
n=1 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)
n=1 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)
n=4 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)
n=3 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)
n=3 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)
n=4 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)
n=4 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
n=6 participants at risk
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Gastrointestinal -Other (bloating)
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Edema:limb
|
0.00%
0/1
|
0.00%
0/1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/1
|
0.00%
0/1
|
25.0%
1/4 • Number of events 1
|
0.00%
0/3
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Sodium, serum-high (hypernatremia)
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
25.0%
1/4 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
|
Nervous system disorders
Memory impairment
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Hiccoughs (hiccups, singultus)
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
|
Immune system disorders
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)
|
0.00%
0/1
|
0.00%
0/1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Cardiac disorders
Hypertension
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Pruritis/itching
|
0.00%
0/1
|
0.00%
0/1
|
33.3%
2/6 • Number of events 2
|
0.00%
0/1
|
100.0%
1/1 • Number of events 1
|
0.00%
0/4
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
50.0%
2/4 • Number of events 2
|
0.00%
0/4
|
0.00%
0/6
|
|
Gastrointestinal disorders
Gastritis (including bile reflux gastritis)
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
|
Hepatobiliary disorders
Liver dysfunction/failure (clinical)
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
PTT (Partial Thromboplastin TIme)
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
66.7%
4/6 • Number of events 4
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
50.0%
2/4 • Number of events 2
|
66.7%
2/3 • Number of events 2
|
66.7%
2/3 • Number of events 2
|
75.0%
3/4 • Number of events 3
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Hemoglobin
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
6/6 • Number of events 6
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
4/4 • Number of events 4
|
66.7%
2/3 • Number of events 2
|
100.0%
3/3 • Number of events 3
|
100.0%
4/4 • Number of events 4
|
100.0%
4/4 • Number of events 4
|
50.0%
3/6 • Number of events 3
|
|
Blood and lymphatic system disorders
Leukocytes (total WBC)
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
6/6 • Number of events 6
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
4/4 • Number of events 4
|
100.0%
3/3 • Number of events 3
|
100.0%
3/3 • Number of events 3
|
100.0%
4/4 • Number of events 4
|
100.0%
4/4 • Number of events 4
|
100.0%
6/6 • Number of events 6
|
|
Blood and lymphatic system disorders
Lymphopenia
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
6/6 • Number of events 6
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
4/4 • Number of events 4
|
100.0%
3/3 • Number of events 3
|
100.0%
3/3 • Number of events 3
|
100.0%
4/4 • Number of events 4
|
100.0%
4/4 • Number of events 4
|
100.0%
6/6 • Number of events 6
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
6/6 • Number of events 6
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
4/4 • Number of events 4
|
100.0%
3/3 • Number of events 3
|
100.0%
3/3 • Number of events 3
|
100.0%
4/4 • Number of events 4
|
75.0%
3/4 • Number of events 3
|
100.0%
6/6 • Number of events 6
|
|
Blood and lymphatic system disorders
Platelets
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
83.3%
5/6 • Number of events 5
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
4/4 • Number of events 4
|
66.7%
2/3 • Number of events 2
|
100.0%
3/3 • Number of events 3
|
100.0%
4/4 • Number of events 4
|
100.0%
4/4 • Number of events 4
|
100.0%
6/6 • Number of events 6
|
|
Blood and lymphatic system disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)
|
100.0%
1/1 • Number of events 1
|
0.00%
0/1
|
83.3%
5/6 • Number of events 5
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
75.0%
3/4 • Number of events 3
|
33.3%
1/3 • Number of events 1
|
100.0%
3/3 • Number of events 3
|
75.0%
3/4 • Number of events 3
|
100.0%
4/4 • Number of events 4
|
0.00%
0/6
|
|
Gastrointestinal disorders
Nausea
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
66.7%
4/6 • Number of events 4
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
75.0%
3/4 • Number of events 3
|
100.0%
3/3 • Number of events 3
|
100.0%
3/3 • Number of events 3
|
100.0%
4/4 • Number of events 4
|
100.0%
4/4 • Number of events 4
|
50.0%
3/6 • Number of events 3
|
|
Gastrointestinal disorders
Vomiting
|
100.0%
1/1 • Number of events 1
|
0.00%
0/1
|
66.7%
4/6 • Number of events 4
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
75.0%
3/4 • Number of events 3
|
100.0%
3/3 • Number of events 3
|
100.0%
3/3 • Number of events 3
|
75.0%
3/4 • Number of events 3
|
25.0%
1/4 • Number of events 1
|
33.3%
2/6 • Number of events 2
|
|
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
6/6 • Number of events 6
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
4/4 • Number of events 4
|
100.0%
3/3 • Number of events 3
|
100.0%
3/3 • Number of events 3
|
100.0%
4/4 • Number of events 4
|
100.0%
4/4 • Number of events 4
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Pain
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
6/6 • Number of events 6
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
4/4 • Number of events 4
|
100.0%
3/3 • Number of events 3
|
100.0%
3/3 • Number of events 3
|
75.0%
3/4 • Number of events 3
|
100.0%
4/4 • Number of events 4
|
50.0%
3/6 • Number of events 3
|
|
Blood and lymphatic system disorders
Coagulation-Other (thrombotic microangiopathy)
|
0.00%
0/1
|
0.00%
0/1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/1
|
0.00%
0/1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Gastrointestinal disorders
Dry mouth/salivary gland (xerostomia)
|
0.00%
0/1
|
0.00%
0/1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Petechiae/purpura (hemorrhage/bleeding into skin or mucosa)
|
0.00%
0/1
|
0.00%
0/1
|
33.3%
2/6 • Number of events 2
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Immune system disorders
Cytokine release syndrome/acute infusion reaction
|
0.00%
0/1
|
0.00%
0/1
|
33.3%
2/6 • Number of events 2
|
0.00%
0/1
|
0.00%
0/1
|
25.0%
1/4 • Number of events 1
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Vascular disorders
Thrombosis/thrombus/embolism
|
0.00%
0/1
|
0.00%
0/1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Cardiac disorders
Supraventricular and nodal arrhythmia
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
50.0%
2/4 • Number of events 2
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Hair loss/alopecia (scalp or body)
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
25.0%
1/4 • Number of events 1
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Renal and urinary disorders
Hemorrhage, GU
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
25.0%
1/4 • Number of events 1
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
0.00%
0/1
|
0.00%
0/1
|
50.0%
3/6 • Number of events 3
|
100.0%
1/1 • Number of events 1
|
0.00%
0/1
|
25.0%
1/4 • Number of events 1
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
33.3%
2/6 • Number of events 2
|
|
Cardiac disorders
Pleural effusion (non-malignant)
|
0.00%
0/1
|
0.00%
0/1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Death not associated with CTCAE term
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Bruising (in absence of Grade 3 or 4 thrombocytopenia)
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Gastrointestinal disorders
Hemorrhage, GI
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
66.7%
2/3 • Number of events 2
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Hypopigmentation
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Cardiac disorders
Hypotension
|
0.00%
0/1
|
0.00%
0/1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/1
|
0.00%
0/1
|
25.0%
1/4 • Number of events 1
|
0.00%
0/3
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
General disorders
Weight gain
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Gastrointestinal disorders
Taste alteration (dysgeusia)
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Nervous system disorders
Hemorrhage, CNS
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Hepatobiliary disorders
Pancreatitis
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Calcium, serum-high (hypercalcemia)
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Potassium, serum-low (hypokalemia)
|
0.00%
0/1
|
0.00%
0/1
|
33.3%
2/6 • Number of events 2
|
0.00%
0/1
|
0.00%
0/1
|
25.0%
1/4 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
50.0%
2/4 • Number of events 2
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Nervous system disorders
Confusion
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
50.0%
2/4 • Number of events 2
|
0.00%
0/6
|
|
Nervous system disorders
Dizziness
|
0.00%
0/1
|
0.00%
0/1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/1
|
0.00%
0/1
|
100.0%
4/4 • Number of events 4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Nervous system disorders
Mood alteration
|
0.00%
0/1
|
0.00%
0/1
|
33.3%
2/6 • Number of events 2
|
0.00%
0/1
|
100.0%
1/1 • Number of events 1
|
50.0%
2/4 • Number of events 2
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Nervous system disorders
Psychosis (hallucinations/delusions)
|
0.00%
0/1
|
0.00%
0/1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Eye disorders
Vision-blurred vision
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
0.00%
0/1
|
0.00%
0/1
|
33.3%
2/6 • Number of events 2
|
0.00%
0/1
|
0.00%
0/1
|
50.0%
2/4 • Number of events 2
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
0.00%
0/4
|
50.0%
2/4 • Number of events 2
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/1
|
0.00%
0/1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Vascular disorders
Vascular-Other (anasarca)
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
0.00%
0/1
|
0.00%
0/1
|
66.7%
4/6 • Number of events 4
|
0.00%
0/1
|
0.00%
0/1
|
50.0%
2/4 • Number of events 2
|
66.7%
2/3 • Number of events 2
|
100.0%
3/3 • Number of events 3
|
75.0%
3/4 • Number of events 3
|
100.0%
4/4 • Number of events 4
|
33.3%
2/6 • Number of events 2
|
|
General disorders
Rigors/chills
|
100.0%
1/1 • Number of events 1
|
0.00%
0/1
|
50.0%
3/6 • Number of events 3
|
100.0%
1/1 • Number of events 1
|
0.00%
0/1
|
50.0%
2/4 • Number of events 2
|
33.3%
1/3 • Number of events 1
|
66.7%
2/3 • Number of events 2
|
75.0%
3/4 • Number of events 3
|
75.0%
3/4 • Number of events 3
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Sweating (diaphoresis)
|
0.00%
0/1
|
0.00%
0/1
|
50.0%
3/6 • Number of events 3
|
0.00%
0/1
|
0.00%
0/1
|
25.0%
1/4 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
66.7%
2/3 • Number of events 2
|
50.0%
2/4 • Number of events 2
|
25.0%
1/4 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Weight loss
|
0.00%
0/1
|
0.00%
0/1
|
66.7%
4/6 • Number of events 4
|
0.00%
0/1
|
0.00%
0/1
|
75.0%
3/4 • Number of events 3
|
66.7%
2/3 • Number of events 2
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
25.0%
1/4 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Flushing
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
16.7%
1/6 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
16.7%
1/6 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/1
|
0.00%
0/1
|
33.3%
2/6 • Number of events 2
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
66.7%
2/3 • Number of events 2
|
66.7%
2/3 • Number of events 2
|
50.0%
2/4 • Number of events 2
|
75.0%
3/4 • Number of events 3
|
33.3%
2/6 • Number of events 2
|
|
Gastrointestinal disorders
Mucositis/stomatitis (clinical exam)
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
16.7%
1/6 • Number of events 1
|
|
Metabolism and nutrition disorders
Alkaline phosphatase
|
100.0%
1/1 • Number of events 1
|
0.00%
0/1
|
50.0%
3/6 • Number of events 3
|
100.0%
1/1 • Number of events 1
|
0.00%
0/1
|
100.0%
4/4 • Number of events 4
|
66.7%
2/3 • Number of events 2
|
33.3%
1/3 • Number of events 1
|
75.0%
3/4 • Number of events 3
|
100.0%
4/4 • Number of events 4
|
33.3%
2/6 • Number of events 2
|
|
Metabolism and nutrition disorders
Bilirubin (hyperbilirubinemia)
|
0.00%
0/1
|
0.00%
0/1
|
16.7%
1/6 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
0.00%
0/1
|
75.0%
3/4 • Number of events 3
|
33.3%
1/3 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
Metabolism and nutrition disorders
Creatinine
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
25.0%
1/4 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
75.0%
3/4 • Number of events 3
|
16.7%
1/6 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
16.7%
1/6 • Number of events 1
|
|
Nervous system disorders
Neuropathy:sensory
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
16.7%
1/6 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/1
|
0.00%
0/1
|
50.0%
3/6 • Number of events 3
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
66.7%
2/3 • Number of events 2
|
33.3%
1/3 • Number of events 1
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pericardial effusion (non-malignant)
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Calcium, serum-low (hypocalcemia)
|
100.0%
1/1 • Number of events 1
|
0.00%
0/1
|
83.3%
5/6 • Number of events 5
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
4/4 • Number of events 4
|
100.0%
3/3 • Number of events 3
|
100.0%
3/3 • Number of events 3
|
75.0%
3/4 • Number of events 3
|
50.0%
2/4 • Number of events 2
|
16.7%
1/6 • Number of events 1
|
|
Metabolism and nutrition disorders
Magnesium, serum-low (hypomagnesemia)
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
6/6 • Number of events 6
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
4/4 • Number of events 4
|
100.0%
3/3 • Number of events 3
|
100.0%
3/3 • Number of events 3
|
50.0%
2/4 • Number of events 2
|
50.0%
2/4 • Number of events 2
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Phosphate, serum-low (hypophosphatemia)
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
6/6 • Number of events 6
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
4/4 • Number of events 4
|
33.3%
1/3 • Number of events 1
|
100.0%
3/3 • Number of events 3
|
100.0%
4/4 • Number of events 4
|
75.0%
3/4 • Number of events 3
|
33.3%
2/6 • Number of events 2
|
|
Metabolism and nutrition disorders
Sodium, serum-low (hyponatremia)
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
33.3%
2/6 • Number of events 2
|
0.00%
0/1
|
0.00%
0/1
|
75.0%
3/4 • Number of events 3
|
33.3%
1/3 • Number of events 1
|
100.0%
3/3 • Number of events 3
|
75.0%
3/4 • Number of events 3
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
|
Gastrointestinal disorders
Anorexia
|
0.00%
0/1
|
100.0%
1/1 • Number of events 1
|
100.0%
6/6 • Number of events 6
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
4/4 • Number of events 4
|
100.0%
3/3 • Number of events 3
|
66.7%
2/3 • Number of events 2
|
50.0%
2/4 • Number of events 2
|
50.0%
2/4 • Number of events 2
|
16.7%
1/6 • Number of events 1
|
|
Infections and infestations
Febrile neutropenia
|
0.00%
0/1
|
100.0%
1/1 • Number of events 1
|
33.3%
2/6 • Number of events 2
|
0.00%
0/1
|
0.00%
0/1
|
100.0%
4/4 • Number of events 4
|
66.7%
2/3 • Number of events 2
|
100.0%
3/3 • Number of events 3
|
100.0%
4/4 • Number of events 4
|
100.0%
4/4 • Number of events 4
|
83.3%
5/6 • Number of events 5
|
|
Infections and infestations
Infection
|
0.00%
0/1
|
100.0%
1/1 • Number of events 1
|
33.3%
2/6 • Number of events 2
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
75.0%
3/4 • Number of events 3
|
66.7%
2/3 • Number of events 2
|
33.3%
1/3 • Number of events 1
|
25.0%
1/4 • Number of events 1
|
25.0%
1/4 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
Metabolism and nutrition disorders
AST, SGOT (serum glutamic oxaloacetic transaminase)
|
0.00%
0/1
|
100.0%
1/1 • Number of events 1
|
50.0%
3/6 • Number of events 3
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
4/4 • Number of events 4
|
33.3%
1/3 • Number of events 1
|
66.7%
2/3 • Number of events 2
|
100.0%
4/4 • Number of events 4
|
100.0%
4/4 • Number of events 4
|
33.3%
2/6 • Number of events 2
|
|
Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase)
|
0.00%
0/1
|
100.0%
1/1 • Number of events 1
|
66.7%
4/6 • Number of events 4
|
100.0%
1/1 • Number of events 1
|
100.0%
1/1 • Number of events 1
|
100.0%
4/4 • Number of events 4
|
66.7%
2/3 • Number of events 2
|
66.7%
2/3 • Number of events 2
|
100.0%
4/4 • Number of events 4
|
100.0%
4/4 • Number of events 4
|
50.0%
3/6 • Number of events 3
|
|
Metabolism and nutrition disorders
Magnesium, serum-high (hypermagnesemia)
|
0.00%
0/1
|
100.0%
1/1 • Number of events 1
|
33.3%
2/6 • Number of events 2
|
100.0%
1/1 • Number of events 1
|
0.00%
0/1
|
25.0%
1/4 • Number of events 1
|
0.00%
0/3
|
0.00%
0/3
|
25.0%
1/4 • Number of events 1
|
0.00%
0/4
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Uric acid, serum-high (hyperuricemia)
|
0.00%
0/1
|
0.00%
0/1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
25.0%
1/4 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
0.00%
0/4
|
0.00%
0/4
|
0.00%
0/6
|
|
General disorders
Pain-Other (generalized pain)
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/6
|
0.00%
0/1
|
0.00%
0/1
|
0.00%
0/4
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
0.00%
0/4
|
25.0%
1/4 • Number of events 1
|
0.00%
0/6
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place