Trial Outcomes & Findings for Pilot hu14.18-IL2 in Resectable Recurrent Stage III or Stage IV Melanoma (NCT NCT00590824)
NCT ID: NCT00590824
Last Updated: 2019-11-21
Results Overview
Histological analysis of anti-tumor activity is a primary endpoint. This is measured after surgical resection via staining to indicate GD2 expression. The GD2 results were summarized in terms of positive (GD2 expression high or low/moderate) and negative (GD2 expression undetectable).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
23 participants
Primary outcome timeframe
up to 1 week
Results posted on
2019-11-21
Participant Flow
Protocol amended to drop cilengitide groups (C and D), proceed with enrollment and randomization into hu14.18- IL2 groups.
Participant milestones
| Measure |
Group A
Hu14.18-IL2 --\>Resection--\>Hu14.18-IL2
hu14.18-IL2: 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course followed by surgery and up to 2 additional courses of hu14.18-IL2
|
Group B
Resection --\>Hu14.18-IL2--\>Hu14.18-IL2
hu14.18-IL2: Surgery followed by 3 courses of 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course
|
Group C
Cilengitide +Hu14.18-IL2--\>Resection--\>Cilengitide+Hu14.18-IL2
\[This Arm was suspended and subsequently removed from the study design via protocol amendment due to toxicity\]
|
Group D
Cilengitide--\>Resection--\>Cilengitide + Hu14.18-IL2
\[This Arm was suspended and subsequently removed from the study design via protocol amendment due to toxicity\]
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
11
|
9
|
2
|
1
|
|
Overall Study
COMPLETED
|
11
|
7
|
1
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
1
|
1
|
Reasons for withdrawal
| Measure |
Group A
Hu14.18-IL2 --\>Resection--\>Hu14.18-IL2
hu14.18-IL2: 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course followed by surgery and up to 2 additional courses of hu14.18-IL2
|
Group B
Resection --\>Hu14.18-IL2--\>Hu14.18-IL2
hu14.18-IL2: Surgery followed by 3 courses of 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course
|
Group C
Cilengitide +Hu14.18-IL2--\>Resection--\>Cilengitide+Hu14.18-IL2
\[This Arm was suspended and subsequently removed from the study design via protocol amendment due to toxicity\]
|
Group D
Cilengitide--\>Resection--\>Cilengitide + Hu14.18-IL2
\[This Arm was suspended and subsequently removed from the study design via protocol amendment due to toxicity\]
|
|---|---|---|---|---|
|
Overall Study
Disease could not be resected
|
0
|
2
|
1
|
0
|
|
Overall Study
Adverse Event
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Pilot hu14.18-IL2 in Resectable Recurrent Stage III or Stage IV Melanoma
Baseline characteristics by cohort
| Measure |
Group A
n=11 Participants
Hu14.18-IL2 --\>Resection--\>Hu14.18-IL2
hu14.18-IL2: 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course followed by surgery and up to 2 additional courses of hu14.18-IL2
|
Group B
n=9 Participants
Resection --\>Hu14.18-IL2--\>Hu14.18-IL2
hu14.18-IL2: Surgery followed by 3 courses of 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course
|
Group C
n=2 Participants
Cilengitide +Hu14.18-IL2--\>Resection--\>Cilengitide+Hu14.18-IL2
\[This Arm was suspended and subsequently removed from the study design via protocol amendment due to toxicity\]
|
Group D
n=1 Participants
Cilengitide--\>Resection--\>Cilengitide + Hu14.18-IL2
\[This Arm was suspended and subsequently removed from the study design via protocol amendment due to toxicity\]
|
Total
n=23 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
46 years
n=5 Participants
|
52 years
n=7 Participants
|
56 years
n=5 Participants
|
67 years
n=4 Participants
|
47 years
n=21 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
15 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
22 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
22 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
11 participants
n=5 Participants
|
9 participants
n=7 Participants
|
2 participants
n=5 Participants
|
1 participants
n=4 Participants
|
23 participants
n=21 Participants
|
|
ECOG PS
0
|
9 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
19 Participants
n=21 Participants
|
|
ECOG PS
1
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Disease Extent
Extensive
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
|
Disease Extent
Non-extensive
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
16 Participants
n=21 Participants
|
|
Disease Stage
III
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
14 Participants
n=21 Participants
|
|
Disease Stage
IV
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
|
Histology
Cutaneous melanoma
|
10 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
21 Participants
n=21 Participants
|
|
Histology
Unknown melanoma primary
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Histology
Subungual melanoma
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Prior Therapy
Granulocyte-macrophage colony stimulating factor
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
1 participants
n=21 Participants
|
|
Prior Therapy
Chemotherapy multiple agent
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
1 participants
n=21 Participants
|
|
Prior Therapy
Interferon alpha-2b
|
7 participants
n=5 Participants
|
5 participants
n=7 Participants
|
1 participants
n=5 Participants
|
1 participants
n=4 Participants
|
14 participants
n=21 Participants
|
|
Prior Therapy
No prior therapy
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
1 participants
n=21 Participants
|
|
Prior Therapy
Radiation therapy
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
3 participants
n=21 Participants
|
|
Prior Therapy
Surgery
|
10 participants
n=5 Participants
|
9 participants
n=7 Participants
|
2 participants
n=5 Participants
|
1 participants
n=4 Participants
|
22 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: up to 1 weekPopulation: There were 12 participants with evaluable tumor samples for GD2 analysis.
Histological analysis of anti-tumor activity is a primary endpoint. This is measured after surgical resection via staining to indicate GD2 expression. The GD2 results were summarized in terms of positive (GD2 expression high or low/moderate) and negative (GD2 expression undetectable).
Outcome measures
| Measure |
Group A
n=6 Participants
Hu14.18-IL2 --\>Resection--\>Hu14.18-IL2
hu14.18-IL2: 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course followed by surgery and up to 2 additional courses of hu14.18-IL2
|
Group B
n=6 Participants
Resection --\>Hu14.18-IL2--\>Hu14.18-IL2
hu14.18-IL2: Surgery followed by 3 courses of 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course
|
|---|---|---|
|
Ganglioside Expressed by Tumor Cells (GD2)
Positive GD2
|
3 Participants
|
3 Participants
|
|
Ganglioside Expressed by Tumor Cells (GD2)
Negative GD2
|
3 Participants
|
3 Participants
|
PRIMARY outcome
Timeframe: up to 24 monthsPopulation: Two patients in Group B were not treated with adjuvant hu14.18-IL2. Subsequently these two patients were excluded from the RFS analysis. There was no intent in the protocol to compare RFS between Groups A and B.
RFS was defined as the number of days from the day of evaluation following course 2 of immunocytokine treatment to the day the subject experienced an event of recurrence or death, whichever occurred first. Participants who did not experience an event of recurrence or death at the time of analysis were censored at the date of the last evaluation for recurrence.
Outcome measures
| Measure |
Group A
n=18 Participants
Hu14.18-IL2 --\>Resection--\>Hu14.18-IL2
hu14.18-IL2: 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course followed by surgery and up to 2 additional courses of hu14.18-IL2
|
Group B
Resection --\>Hu14.18-IL2--\>Hu14.18-IL2
hu14.18-IL2: Surgery followed by 3 courses of 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course
|
|---|---|---|
|
Recurrence Free Survival (RFS)
|
5.73 months
Interval 1.8 to
the value is infinity (reported as INF)
|
—
|
PRIMARY outcome
Timeframe: up to 24 monthsPopulation: There was no intent in the protocol to compare OS between Groups A and B.
OS was defined as the number of days from randomization to the date of the participant's death. Participants who did not experience an event of death at the time of analysis were censored at the date of the last follow-up.
Outcome measures
| Measure |
Group A
n=20 Participants
Hu14.18-IL2 --\>Resection--\>Hu14.18-IL2
hu14.18-IL2: 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course followed by surgery and up to 2 additional courses of hu14.18-IL2
|
Group B
Resection --\>Hu14.18-IL2--\>Hu14.18-IL2
hu14.18-IL2: Surgery followed by 3 courses of 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course
|
|---|---|---|
|
Overall Survival (OS)
|
61.57 months
Interval 13.67 to
the value is infinity (reported as INF)
|
—
|
SECONDARY outcome
Timeframe: up to 29 daysCRP measured at baseline, cycle 1 day 3, and cycle 2 day 1.
Outcome measures
| Measure |
Group A
n=11 Participants
Hu14.18-IL2 --\>Resection--\>Hu14.18-IL2
hu14.18-IL2: 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course followed by surgery and up to 2 additional courses of hu14.18-IL2
|
Group B
n=7 Participants
Resection --\>Hu14.18-IL2--\>Hu14.18-IL2
hu14.18-IL2: Surgery followed by 3 courses of 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course
|
|---|---|---|
|
C-Reactive Protein (CRP)
baseline
|
0 mg/dL
Interval 0.0 to 9.0
|
0 mg/dL
Interval 0.0 to 1.0
|
|
C-Reactive Protein (CRP)
cycle 1 day 3
|
9 mg/dL
Interval 7.0 to 14.0
|
11 mg/dL
Interval 6.0 to 13.0
|
|
C-Reactive Protein (CRP)
cycle 2 day 1
|
0 mg/dL
Interval 0.0 to 7.0
|
0 mg/dL
Interval 0.0 to 4.0
|
SECONDARY outcome
Timeframe: up to 29 daysLymphocyte count measured at baseline, cycle 1 day 3, cycle 1 day 8, and cycle 2 day 1
Outcome measures
| Measure |
Group A
n=11 Participants
Hu14.18-IL2 --\>Resection--\>Hu14.18-IL2
hu14.18-IL2: 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course followed by surgery and up to 2 additional courses of hu14.18-IL2
|
Group B
n=7 Participants
Resection --\>Hu14.18-IL2--\>Hu14.18-IL2
hu14.18-IL2: Surgery followed by 3 courses of 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course
|
|---|---|---|
|
Lymphocyte Count
cycle 1 day 8
|
4910 number of lymphocytes
Interval 2610.0 to 6954.0
|
3900 number of lymphocytes
Interval 2420.0 to 4470.0
|
|
Lymphocyte Count
baseline
|
1750 number of lymphocytes
Interval 1090.0 to 2430.0
|
1440 number of lymphocytes
Interval 960.0 to 2300.0
|
|
Lymphocyte Count
cycle 1 day 3
|
200 number of lymphocytes
Interval 62.0 to 460.0
|
250 number of lymphocytes
Interval 170.0 to 270.0
|
|
Lymphocyte Count
cycle 2 day 1
|
3160 number of lymphocytes
Interval 1790.0 to 4110.0
|
2100 number of lymphocytes
Interval 1730.0 to 3080.0
|
SECONDARY outcome
Timeframe: up to 12 weeksPopulation: Based on data collected from prior trials and analyzed during the time of this trial, the day 3 sample (obtained during hu14.18-IL2 administration) was potentially "masked" by the infusion of the immunocytokine. Anti-immunocytokine antibodies were not typically generated during the initial 5 days when infusions were given on days 1-3.
Detection of anti-idiotypic will be performed on participants' serum obtained approximately 10 minutes prior to initiation of treatment, and serum samples on Days 3, 4, 8, and 29/1 of 3 cycles.
Outcome measures
| Measure |
Group A
n=11 Participants
Hu14.18-IL2 --\>Resection--\>Hu14.18-IL2
hu14.18-IL2: 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course followed by surgery and up to 2 additional courses of hu14.18-IL2
|
Group B
n=7 Participants
Resection --\>Hu14.18-IL2--\>Hu14.18-IL2
hu14.18-IL2: Surgery followed by 3 courses of 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course
|
|---|---|---|
|
Anti-Idiotypic Antibodies
Cycle 1 Day 1 pre-treatment
|
0.2 Optical Density (OD)
Standard Error 0.09
|
0.2 Optical Density (OD)
Standard Error 0.12
|
|
Anti-Idiotypic Antibodies
Cycle 1 Day 4
|
0.4 Optical Density (OD)
Standard Error 0.11
|
0.8 Optical Density (OD)
Standard Error 0.33
|
|
Anti-Idiotypic Antibodies
Cycle 1 Day 8
|
1.5 Optical Density (OD)
Standard Error 0.23
|
1.7 Optical Density (OD)
Standard Error 0.42
|
|
Anti-Idiotypic Antibodies
End Cycle 1
|
0.6 Optical Density (OD)
Standard Error 0.24
|
0.6 Optical Density (OD)
Standard Error 0.18
|
|
Anti-Idiotypic Antibodies
Cycle 2 Day 1 pre-treatment
|
0.4 Optical Density (OD)
Standard Error 0.11
|
0.5 Optical Density (OD)
Standard Error 0.13
|
|
Anti-Idiotypic Antibodies
Cycle 2 Day 4
|
0.4 Optical Density (OD)
Standard Error 0.16
|
0.5 Optical Density (OD)
Standard Error 0.17
|
|
Anti-Idiotypic Antibodies
Cycle 2 Day 8
|
1.5 Optical Density (OD)
Standard Error 0.31
|
1.4 Optical Density (OD)
Standard Error 0.23
|
|
Anti-Idiotypic Antibodies
End Cycle 2
|
0.9 Optical Density (OD)
Standard Error 0.24
|
0.6 Optical Density (OD)
Standard Error 0.16
|
|
Anti-Idiotypic Antibodies
Cycle 3 Day 1 pre-treatment
|
0.9 Optical Density (OD)
Standard Error 0.28
|
0.5 Optical Density (OD)
Standard Error 0.14
|
|
Anti-Idiotypic Antibodies
Cycle 3 Day 4
|
0.4 Optical Density (OD)
Standard Error 0.09
|
0.6 Optical Density (OD)
Standard Error 0.16
|
|
Anti-Idiotypic Antibodies
Cycle 3 Day 8
|
1.0 Optical Density (OD)
Standard Error 0.30
|
1.2 Optical Density (OD)
Standard Error 0.28
|
|
Anti-Idiotypic Antibodies
End Cycle 3
|
0.7 Optical Density (OD)
Standard Error 0.27
|
0.5 Optical Density (OD)
Standard Error 0.12
|
SECONDARY outcome
Timeframe: up to 12 weeksPopulation: The investigators determined in real time that the evaluation of anti-Fc-Il2 antibodies was not an appropriate biomarker for this study. The patient generated "anti-drug antibody," specific for the Fc-IL2 component of the immunocytokine is detected in the standard "anti-idiotypic" bridge assay (reported in Outcome Measure 6).
Detection of anti-FcIL2 will be performed on participants' serum obtained approximately 10 minutes prior to initiation of treatment, and serum samples on Days 3, 4, 8, and 29/1, for 3 cycles
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: up to 12 weeksSoluble IL2 receptor α levels will be performed on participants approximately 10 minutes prior to initiation of treatment, and serum samples on Days 3, 4, 8, and 29/1.
Outcome measures
| Measure |
Group A
n=11 Participants
Hu14.18-IL2 --\>Resection--\>Hu14.18-IL2
hu14.18-IL2: 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course followed by surgery and up to 2 additional courses of hu14.18-IL2
|
Group B
n=7 Participants
Resection --\>Hu14.18-IL2--\>Hu14.18-IL2
hu14.18-IL2: Surgery followed by 3 courses of 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course
|
|---|---|---|
|
In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels
Cycle 2 Day 4
|
12439.5 ng/ml
Standard Error 1670.7
|
11101.1 ng/ml
Standard Error 1168.9
|
|
In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels
Cycle 2 Day 8
|
6481.0 ng/ml
Standard Error 769.5
|
6124.0 ng/ml
Standard Error 772.1
|
|
In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels
10 min prior to initiation of Cycle 1 treatment
|
1293.0 ng/ml
Standard Error 150.1
|
1229.7 ng/ml
Standard Error 260.8
|
|
In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels
Cycle 1 Day 3
|
6669.0 ng/ml
Standard Error 913.8
|
6285.8 ng/ml
Standard Error 598.2
|
|
In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels
Cycle 1 Day 4
|
10837.5 ng/ml
Standard Error 1299.4
|
7378.5 ng/ml
Standard Error 770.8
|
|
In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels
Cycle 1 Day 8
|
5913.8 ng/ml
Standard Error 614.8
|
4405.0 ng/ml
Standard Error 639.8
|
|
In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels
Cycle 1 End
|
2010.8 ng/ml
Standard Error 187.7
|
1723.0 ng/ml
Standard Error 127.9
|
|
In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels
10 min prior to initiation of Cycle 2 treatment
|
1606.0 ng/ml
Standard Error 169.8
|
1547.1 ng/ml
Standard Error 196.82
|
|
In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels
Cycle 2 Day 3
|
7643.6 ng/ml
Standard Error 1037.8
|
7017.7 ng/ml
Standard Error 694.9
|
|
In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels
Cycle 2 End
|
2065.9 ng/ml
Standard Error 200.3
|
1931.7 ng/ml
Standard Error 187.4
|
|
In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels
10 min prior to initiation of Cycle 3
|
2077.4 ng/ml
Standard Error 188.6
|
1901.0 ng/ml
Standard Error 214.3
|
|
In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels
Cycle 3 Day 3
|
9515.1 ng/ml
Standard Error 1760.6
|
7636.7 ng/ml
Standard Error 887.3
|
|
In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels
Cycle 3 Day 4
|
13907.1 ng/ml
Standard Error 2319.7
|
13029.0 ng/ml
Standard Error 1204.9
|
|
In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels
Cycle 3 Day 8
|
6705.8 ng/ml
Standard Error 802.0
|
6879.2 ng/ml
Standard Error 506.9
|
|
In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels
Cycle 3 End
|
2334.8 ng/ml
Standard Error 289.8
|
2198.8 ng/ml
Standard Error 321.5
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 1 weekOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: up to 1 weekOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 1 weekOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 1 weekOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 1 weekOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 1 weekOutcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: up to 12 weeksNK and ADCC testing will be done on selected patients with freshly collected peripheral blood mononuclear cell (PBMC) at baseline (as a control), on day 8 of Courses 2 and 3, and on day 29/1 of Courses 2 and 3.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: up to 12 weeksNK and ADCC testing will be done on selected patients with freshly collected peripheral blood mononuclear cell (PBMC) at baseline (as a control), on day 8 of Courses 2 and 3, and on day 29/1 of Courses 2 and 3.
Outcome measures
Outcome data not reported
Adverse Events
Group A
Serious events: 2 serious events
Other events: 10 other events
Deaths: 4 deaths
Group B
Serious events: 2 serious events
Other events: 7 other events
Deaths: 5 deaths
Group C
Serious events: 0 serious events
Other events: 2 other events
Deaths: 1 deaths
Group D
Serious events: 1 serious events
Other events: 1 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Group A
n=11 participants at risk
Hu14.18-IL2 --\>Resection--\>Hu14.18-IL2
hu14.18-IL2: 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course followed by surgery and up to 2 additional courses of hu14.18-IL2
|
Group B
n=9 participants at risk
Resection --\>Hu14.18-IL2--\>Hu14.18-IL2
hu14.18-IL2: Surgery followed by 3 courses of 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course
|
Group C
n=2 participants at risk
Cilengitide +Hu14.18-IL2--\>Resection--\>Cilengitide+Hu14.18-IL2
\[This Arm was suspended and subsequently removed from the study design via protocol amendment due to toxicity\]
|
Group D
n=1 participants at risk
Cilengitide--\>Resection--\>Cilengitide + Hu14.18-IL2
\[This Arm was suspended and subsequently removed from the study design via protocol amendment due to toxicity\]
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Lymphopenia
|
9.1%
1/11 • Number of events 2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
11.1%
1/9 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
General disorders
Pain - Head / Headache
|
9.1%
1/11 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/9 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Gastrointestinal disorders
Vomiting
|
9.1%
1/11 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/9 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Infections and infestations
Infection
|
0.00%
0/11 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
11.1%
1/9 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Nervous system disorders
Neuropathy
|
0.00%
0/11 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/9 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
100.0%
1/1 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
Other adverse events
| Measure |
Group A
n=11 participants at risk
Hu14.18-IL2 --\>Resection--\>Hu14.18-IL2
hu14.18-IL2: 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course followed by surgery and up to 2 additional courses of hu14.18-IL2
|
Group B
n=9 participants at risk
Resection --\>Hu14.18-IL2--\>Hu14.18-IL2
hu14.18-IL2: Surgery followed by 3 courses of 6 mg/m2 hu14.18-IL2 administered via IV on days 1, 2, and 3 of a 28-day course
|
Group C
n=2 participants at risk
Cilengitide +Hu14.18-IL2--\>Resection--\>Cilengitide+Hu14.18-IL2
\[This Arm was suspended and subsequently removed from the study design via protocol amendment due to toxicity\]
|
Group D
n=1 participants at risk
Cilengitide--\>Resection--\>Cilengitide + Hu14.18-IL2
\[This Arm was suspended and subsequently removed from the study design via protocol amendment due to toxicity\]
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Lymphopenia
|
90.9%
10/11 • Number of events 21 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
77.8%
7/9 • Number of events 18 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
100.0%
2/2 • Number of events 3 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
100.0%
1/1 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
General disorders
Pain
|
9.1%
1/11 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/9 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
9.1%
1/11 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
11.1%
1/9 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Musculoskeletal and connective tissue disorders
Seroma
|
9.1%
1/11 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/9 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
9.1%
1/11 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/9 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Metabolism and nutrition disorders
Metabolic / Lab
|
9.1%
1/11 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/9 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Nervous system disorders
Syncope
|
0.00%
0/11 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
11.1%
1/9 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Metabolism and nutrition disorders
Hyperbilirubinemia
|
0.00%
0/11 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
11.1%
1/9 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
0.00%
0/11 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
11.1%
1/9 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Blood and lymphatic system disorders
Leukocytes (total WBC)
|
0.00%
0/11 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
11.1%
1/9 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Skin and subcutaneous tissue disorders
Pruritus/itching
|
0.00%
0/11 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
22.2%
2/9 • Number of events 2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
0.00%
0/11 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
11.1%
1/9 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Metabolism and nutrition disorders
AST, SGOT(serum glutamic oxaloacetic transaminase)
|
0.00%
0/11 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
11.1%
1/9 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Nervous system disorders
Memory Impairment
|
0.00%
0/11 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/9 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
100.0%
1/1 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Vascular disorders
Hypotension
|
0.00%
0/11 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/9 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
100.0%
1/1 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Vascular disorders
Hypertension
|
0.00%
0/11 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/9 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
100.0%
1/1 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Nervous system disorders
Confusion
|
0.00%
0/11 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/9 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
100.0%
1/1 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Nervous system disorders
Speech Impairment
|
0.00%
0/11 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/9 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
100.0%
1/1 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Nervous system disorders
Cognitive Disturbance
|
0.00%
0/11 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/9 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
100.0%
1/1 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Cardiac disorders
Vasovagal Episode
|
0.00%
0/11 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/9 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
100.0%
1/1 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Nervous system disorders
Somnolence
|
0.00%
0/11 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/9 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
100.0%
1/1 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
|
Blood and lymphatic system disorders
Hematoma
|
0.00%
0/11 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/9 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
0.00%
0/2 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
100.0%
1/1 • Number of events 1 • up to 24 months
Only Grade 3 and 4 Adverse Events (AEs) and AEs requiring dose modification are reported for this study.
|
Additional Information
Paul Sondel, MD, PhD
University of Madison Carbone Cancer Center
Phone: (608) 263-9069
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place