Trial Outcomes & Findings for Use of IL-15 After Chemotherapy and Lymphocyte Transfer in Metastatic Melanoma (NCT NCT01369888)
NCT ID: NCT01369888
Last Updated: 2015-01-27
Results Overview
Intravenous recombinant IL-15 as a daily intravenous bolus for 10 consecutive days in patients with metastatic melanoma who have received a lymphodepleting chemotherapy and ACT TIL with dose escalation (i.e., dose level 1: 0.25 mcg, dose level 2: 0.50 mcg, dose level 3: 1 mcg, and dose level 4: 2 mcg) to further characterize the safety of the MTD prior to starting the phase 2 portion.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
3 participants
Primary outcome timeframe
2 years
Results posted on
2015-01-27
Participant Flow
Protocol was closed due to autoimmune toxicity unlikely related to cells and probably related to the IL-15 injection seen in one pt and also due to the opening of additional surgery branch protocols suggesting pt accrual would not increase in this protocol. The maximum tolerated dose (MTD) was not determined and it did not enter the phase 2 stage.
Participant milestones
| Measure |
IL-15 Following Young TIL (0.25 mcg)
0.25 mcg/kg/day x 10
Cyclophosphamide: 60 mg/m\^2, intravenous (IV) (in the vein) x 2 days
Fludarabine: 25 mg/m\^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0
IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.
|
IL-15 Following Young TIL (0.50 mcg)
0.50 mcg/kg/day x 10
Cyclophosphamide: 60 mg/m\^2, intravenous (IV) (in the vein) x 2 days
Fludarabine: 25 mg/m\^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0
IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.
|
IL-15 Following Young TIL (1 mcg)
1 mcg/kg/day x 10
Cyclophosphamide: 60 mg/m\^2, intravenous (IV) (in the vein) x 2 days
Fludarabine: 25 mg/m\^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0
IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.
|
IL-15 Following Young TIL (2 mcg)
2 mcg/kg/day x 10
Cyclophosphamide: 60 mg/m\^2, intravenous (IV) (in the vein) x 2 days
Fludarabine: 25 mg/m\^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0
IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
1
|
2
|
0
|
0
|
|
Overall Study
COMPLETED
|
1
|
2
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Use of IL-15 After Chemotherapy and Lymphocyte Transfer in Metastatic Melanoma
Baseline characteristics by cohort
| Measure |
IL-15 Following Young TIL (0.25 mcg)
n=1 Participants
0.25 mcg/kg/day x 10
Cyclophosphamide: 60 mg/m\^2, intravenous (IV) (in the vein) x 2 days
Fludarabine: 25 mg/m\^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0
IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.
|
IL-15 Following Young TIL (0.50 mcg)
n=2 Participants
0.50 mcg/kg/day x 10
Cyclophosphamide: 60 mg/m\^2, intravenous (IV) (in the vein) x 2 days
Fludarabine: 25 mg/m\^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0
IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.
|
IL-15 Following Young TIL (10.50 mcg)
1 mcg/kg/day x 10
Cyclophosphamide: 60 mg/m\^2, intravenous (IV) (in the vein) x 2 days
Fludarabine: 25 mg/m\^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0
IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.
|
IL-15 Following Young TIL (2 mcg)
2 mcg/kg/day x 10
Cyclophosphamide: 60 mg/m\^2, intravenous (IV) (in the vein) x 2 days
Fludarabine: 25 mg/m\^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0
IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.
|
Total
n=3 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
—
|
—
|
0 participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
—
|
—
|
3 participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
—
|
—
|
0 participants
n=21 Participants
|
|
Age, Continuous
|
61.0 years
n=5 Participants
|
38. years
STANDARD_DEVIATION 5.7 • n=7 Participants
|
—
|
—
|
45.7 years
STANDARD_DEVIATION 13.9 • n=21 Participants
|
|
Gender
Female
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
—
|
—
|
0 participants
n=21 Participants
|
|
Gender
Male
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
—
|
—
|
3 participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
—
|
—
|
0 participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
—
|
—
|
3 participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
—
|
—
|
0 participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
—
|
—
|
0 participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
—
|
—
|
0 participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
—
|
—
|
0 participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
—
|
—
|
0 participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
—
|
—
|
3 participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
—
|
—
|
0 participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
—
|
—
|
0 participants
n=21 Participants
|
|
Region of Enrollment
United States
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
—
|
—
|
3 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 2 yearsIntravenous recombinant IL-15 as a daily intravenous bolus for 10 consecutive days in patients with metastatic melanoma who have received a lymphodepleting chemotherapy and ACT TIL with dose escalation (i.e., dose level 1: 0.25 mcg, dose level 2: 0.50 mcg, dose level 3: 1 mcg, and dose level 4: 2 mcg) to further characterize the safety of the MTD prior to starting the phase 2 portion.
Outcome measures
| Measure |
IL-15 Following Young TIL (0.25 mcg)
n=1 Participants
0.25 mcg/kg/day x 10
Cyclophosphamide: 60 mg/m\^2, intravenous (IV) (in the vein) x 2 days
Fludarabine: 25 mg/m\^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0
IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.
|
IL-15 Following Young TIL (0.50 mcg)
n=2 Participants
0.50 mcg/kg/day x 10
Cyclophosphamide: 60 mg/m\^2, intravenous (IV) (in the vein) x 2 days
Fludarabine: 25 mg/m\^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0
IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.
|
|---|---|---|
|
Phase 1: Maximum Tolerated Dose (MTD) of Intravenous Recombinant IL-15 as a Daily Intravenous Bolus for 10 Consecutive Days in Patients With Metastatic Melanoma Who Have Received a Lymphodepleting Chemotherapy and ACT TIL.
|
NA mcg/kg/day
The MTD was not determined due to the autoimmune toxicity and it did not enter the phase 2 stage.
|
NA mcg/kg/day
The MTD was not determined due to the autoimmune toxicity and it did not enter the phase 2 stage.
|
PRIMARY outcome
Timeframe: 8 months, 9 daysHere is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Outcome measures
| Measure |
IL-15 Following Young TIL (0.25 mcg)
n=1 Participants
0.25 mcg/kg/day x 10
Cyclophosphamide: 60 mg/m\^2, intravenous (IV) (in the vein) x 2 days
Fludarabine: 25 mg/m\^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0
IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.
|
IL-15 Following Young TIL (0.50 mcg)
n=2 Participants
0.50 mcg/kg/day x 10
Cyclophosphamide: 60 mg/m\^2, intravenous (IV) (in the vein) x 2 days
Fludarabine: 25 mg/m\^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0
IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.
|
|---|---|---|
|
Number of Participants With Adverse Events
|
1 participants
|
2 participants
|
Adverse Events
IL-15 Following Young TIL (0.25 mcg)
Serious events: 1 serious events
Other events: 1 other events
Deaths: 0 deaths
IL-15 Following Young TIL (0.50 mcg)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
IL-15 Following Young TIL (0.25 mcg)
n=1 participants at risk
0.25 mcg/kg/day x 10
Cyclophosphamide: 60 mg/m\^2, intravenous (IV) (in the vein) x 2 days
Fludarabine: 25 mg/m\^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0
IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.
|
IL-15 Following Young TIL (0.50 mcg)
n=2 participants at risk
0.50 mcg/kg/day x 10
Cyclophosphamide: 60 mg/m\^2, intravenous (IV) (in the vein) x 2 days
Fludarabine: 25 mg/m\^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0
IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.
|
|---|---|---|
|
Immune system disorders
Autoimmune reaction
|
100.0%
1/1 • Number of events 1
|
0.00%
0/2
|
Other adverse events
| Measure |
IL-15 Following Young TIL (0.25 mcg)
n=1 participants at risk
0.25 mcg/kg/day x 10
Cyclophosphamide: 60 mg/m\^2, intravenous (IV) (in the vein) x 2 days
Fludarabine: 25 mg/m\^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0
IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.
|
IL-15 Following Young TIL (0.50 mcg)
n=2 participants at risk
0.50 mcg/kg/day x 10
Cyclophosphamide: 60 mg/m\^2, intravenous (IV) (in the vein) x 2 days
Fludarabine: 25 mg/m\^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)
Tumor Infiltrating Lymphocytes: IV over 30 minutes on day 0
IL-15: IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.
|
|---|---|---|
|
Blood and lymphatic system disorders
Leukocytes (total WBC)
|
100.0%
1/1 • Number of events 1
|
100.0%
2/2 • Number of events 2
|
|
Blood and lymphatic system disorders
Lymphopenia
|
100.0%
1/1 • Number of events 1
|
100.0%
2/2 • Number of events 2
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
100.0%
1/1 • Number of events 1
|
100.0%
2/2 • Number of events 2
|
|
Blood and lymphatic system disorders
Platelets
|
100.0%
1/1 • Number of events 1
|
100.0%
2/2 • Number of events 2
|
|
Gastrointestinal disorders
Mucositis/stomatitis
|
100.0%
1/1 • Number of events 1
|
0.00%
0/2
|
|
Infections and infestations
Infection
|
100.0%
1/1 • Number of events 1
|
0.00%
0/2
|
|
Blood and lymphatic system disorders
Edema: limb
|
100.0%
1/1 • Number of events 1
|
0.00%
0/2
|
|
Nervous system disorders
Cognitive disturbances
|
100.0%
1/1 • Number of events 1
|
0.00%
0/2
|
|
Nervous system disorders
Psychosis (hallucinations/delusions)
|
100.0%
1/1 • Number of events 1
|
0.00%
0/2
|
|
General disorders
Pain
|
0.00%
0/1
|
100.0%
2/2 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
100.0%
1/1 • Number of events 1
|
0.00%
0/2
|
|
Ear and labyrinth disorders
Otitis, middle ear (non-infectious)
|
0.00%
0/1
|
50.0%
1/2 • Number of events 1
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
0.00%
0/1
|
50.0%
1/2 • Number of events 1
|
|
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)
|
0.00%
0/1
|
50.0%
1/2 • Number of events 1
|
|
General disorders
Rigors/chills
|
0.00%
0/1
|
50.0%
1/2 • Number of events 1
|
|
General disorders
Sweating (diaphoresis)
|
0.00%
0/1
|
50.0%
1/2 • Number of events 1
|
|
General disorders
Weight loss
|
0.00%
0/1
|
50.0%
1/2 • Number of events 1
|
|
Endocrine disorders
Hot flashes/flushes
|
0.00%
0/1
|
50.0%
1/2 • Number of events 1
|
|
Gastrointestinal disorders
Anorexia
|
0.00%
0/1
|
50.0%
1/2 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/1
|
50.0%
1/2 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/1
|
50.0%
1/2 • Number of events 1
|
|
Infections and infestations
Febrile neutropenia
|
0.00%
0/1
|
100.0%
2/2 • Number of events 2
|
|
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)
|
0.00%
0/1
|
50.0%
1/2 • Number of events 1
|
|
Metabolism and nutrition disorders
Calcium, serum-low (hypocalcemia)
|
0.00%
0/1
|
50.0%
1/2 • Number of events 1
|
|
Metabolism and nutrition disorders
Magnesium, serum-low (hypomagnesemia)
|
0.00%
0/1
|
50.0%
1/2 • Number of events 1
|
|
Metabolism and nutrition disorders
Phosphate, serum-low (hypophosphatemia)
|
0.00%
0/1
|
50.0%
1/2 • Number of events 1
|
|
Nervous system disorders
Syncope (fainting)
|
0.00%
0/1
|
50.0%
1/2 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
0.00%
0/1
|
50.0%
1/2 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place