Melanoma
Conditions
Keywords
Melanoma, hu14.18-IL2
Brief summary
Evaluate the antitumor activity of hu14.18-IL2 in the minimal residual disease setting. Evaluate the time to recurrence and overall survival of patients treated with hu14.18-IL2.
Interventions
DRUGhu14.18-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
Sponsors
National Cancer Institute (NCI)
EMD Serono
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects must have recurrent stage III (i.e., recurrent regional metastasis), or stage IV (i.e., any distant metastasis) melanoma for which surgical resection would be clinically recommended, with biopsy proven (current or previous) Stage III or Stage IV disease. Any biopsies obtained to demonstrate recurrent regional metastasis or distant metastasis must be considered clinically appropriate for clinical management and must not be performed solely for meeting eligibility criteria. In addition, subjects must have disease that has not yet been completely excised. 2. Patients must have disease which involves 3 or fewer sites. A nodal basin recurrence will be scored as one site, even if multiple nodes are positive. Clustered subcutaneous and/or cutaneous lesions that can be removed in a single surgical excision will be scored as one site, even if multiple subcutaneous and/or cutaneous lesions are present. 3. The subjects' disease is determined to be completely resectable with uninvolved margins using standard surgical guidelines based on physical exam and radiographic imaging (MRI or CT of the head, and CT or MRI of the chest, abdomen and pelvis). 4. Subjects must have one of the following: a) Stage III melanoma with recurrence after prior surgery, with or without subsequent adjuvant systemic (standard or experimental) and/or radiotherapy management Or b) Stage IV melanoma (cutaneous, ocular, mucosal, or unknown primary) 5. Subjects must be 18 years old or older OR if they are 15 years old or greater, considered to be mature minors, able to give adult informed consent (with parental co-signature), meet all other eligibility criteria, and also weigh at least 45 kg.. Subjects must weigh at least 45 kg in order to safely provide sufficient blood for monitoring studies (see section 7.7 for details). 6. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Subjects must have adequate bone marrow, liver, and renal function. 8. Subjects with one or more of the following cardiac risk factors must complete a stress radionuclide scan with no evidence of myocardial ischemia or heart failure: (a) a history of cardiac disease, (b) age greater than 65 years old, (c) any clinically significant abnormality found on ECG (required at baseline), or (d) significant risk factors for coronary artery disease (history of significant dyslipidemia; any treatment for dyslipidemia; or two first degree relatives with a documented myocardial infarction prior to age 55). 9. Subjects with significant history of pulmonary disease, shortness of breath at rest, or known Chronic Obstructive Pulmonary Disease (COPD) must have pulmonary function tests within 35% of normal age-predicted values. 10. Subjects must be willing and able to provide informed written consent prior to any study-related procedures. 11. Subjects must have no immediate requirements for palliative chemotherapy, palliative radiotherapy, or palliative hormonal therapy. 12. Subjects must be willing and able to discontinue antihypertensive medications if advised to do so for days of hu14.18-IL2 infusion. 13. Subjects must have slides available from stage III or stage IV melanoma. Paraffin blocks are preferable, but at a minimum, slides documenting melanoma by biopsy (including fine needle cytology) must be available for pathology review, and potential restaining/staining (see Section 7.4, Surgical Pathology Guidelines). Prior histologic demonstration of metastatic melanoma (either stage III or Stage IV) may be utilized if a repeat biopsy is not clinically needed to to establish eligibility.
Exclusion criteria
1. Subjects are ineligible if they have received monoclonal antibodies (mAb) during biologic therapy, tumor imaging, purging of autologous marrow/stem cells for re-infusion or for any other reason unless serological testing is performed. If the absence of detectable antibody (over background) to hu14.18 is documented, the subject is eligible for the study. 2. Subjects treated with IL2 in the past that developed intolerable (Grade 4) IL2-related side effects are not eligible. 3. Subjects who have received any (standard or experimental) systemic therapy for stage IV disease are not eligible. 4. Women of childbearing potential will be excluded if they are pregnant, nursing, or not using effective contraception during the treatment period. 5. Subjects with symptoms of ischemic cardiac disease, congestive heart failure, myocardial infarct within the immediate preceding 6 months and/or uncontrolled cardiac rhythm disturbance are ineligible. 6. Subjects with significant psychiatric disabilities or seizure disorders are ineligible. 7. Subjects who have had major surgery within the past 3 weeks are ineligible. 8. Subjects with clinically detectable pleural effusions or ascites are ineligible. 9. Subjects with organ allografts are ineligible. 10. Subjects who require or are likely to require corticosteroid or other immunosuppressive drugs or have used them within 2 weeks of registration are ineligible. 11. Subjects with significant intercurrent illnesses are ineligible. 12. Subjects with active infections or active peptic ulcer unless these conditions are corrected or controlled are ineligible. 13. Subjects with brain metastases, whether active or inactive, are ineligible. A head MRI or head CT scan will be required at baseline to rule out silent metastases. 14. Subjects with active second malignancy other than non-melanoma skin cancer are ineligible. Patients will be considered eligible if they have been continuously disease free for \> 5 years prior to the time of enrollment. 15. Subjects who are infected with human immunodeficiency virus (HIV), hepatitis B surface antigen (HBs Ag) carrier state or with clinical evidence of hepatitis are ineligible. Treatment may be initiated before laboratory confirmation of HIV and HBs Ag negativity, but will be stopped if results are positive. 16. Subjects with a clinically significant neurologic deficit or objective peripheral neuropathy (Grade \> 2) are ineligible. 17. Subjects with a known hypersensitivity to the study drug, Tween-80® or to human immunoglobulin are ineligible. 18. Patients with a known history of diabetes mellitus that has required systemic therapy within the past 3 months (either oral hypoglycemic agents or insulin) will be excluded, as treatment with hu14.18-IL2 may alter blood glucose levels. 19. Subjects with a legal incapacity or limited legal capacity are ineligible. 20. Subjects with bone metastases are ineligible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ganglioside Expressed by Tumor Cells (GD2) | up to 1 week | 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). |
| Overall Survival (OS) | up to 24 months | 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. |
| Recurrence Free Survival (RFS) | up to 24 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| C-Reactive Protein (CRP) | up to 29 days | CRP measured at baseline, cycle 1 day 3, and cycle 2 day 1. |
| Lymphocyte Count | up to 29 days | Lymphocyte count measured at baseline, cycle 1 day 3, cycle 1 day 8, and cycle 2 day 1 |
| Anti-Idiotypic Antibodies | up to 12 weeks | 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. |
| Anti-Fc-IL2 Antibodies | up to 12 weeks | 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 |
| In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | up to 12 weeks | Soluble 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Interferon Gamma (INF-y) Expression | Up to 1 week | — |
| T Cell Reactivity | Up to 1 week | — |
| Expression of GD2 Target Antigen | Up to 1 week | — |
| Density of Cellular Infiltrate | Up to 1 week | — |
| Tumor Vascularity | Up to 1 week | — |
| Immunocytokine (IC) Binding | up to 1 week | — |
| Natural Killer Cells (NK) | up to 12 weeks | NK 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. |
| Antibody Dependent Cellular Cytotoxicity (ADCC) | up to 12 weeks | NK 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. |
Countries
United States
Participant flow
Pre-assignment details
Protocol amended to drop cilengitide groups (C and D), proceed with enrollment and randomization into hu14.18- IL2 groups.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 11 |
| 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 | 9 |
| Group C Cilengitide +Hu14.18-IL2--\>Resection--\>Cilengitide+Hu14.18-IL2
\[This Arm was suspended and subsequently removed from the study design via protocol amendment due to toxicity\] | 2 |
| Group D Cilengitide--\>Resection--\>Cilengitide + Hu14.18-IL2
\[This Arm was suspended and subsequently removed from the study design via protocol amendment due to toxicity\] | 1 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 |
| Overall Study | Disease could not be resected | 0 | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Group A | Total | Group D | Group C | Group B |
|---|---|---|---|---|---|
| Age, Continuous | 46 years | 47 years | 67 years | 56 years | 52 years |
| Disease Extent Extensive | 4 Participants | 7 Participants | 0 Participants | 1 Participants | 2 Participants |
| Disease Extent Non-extensive | 7 Participants | 16 Participants | 1 Participants | 1 Participants | 7 Participants |
| Disease Stage III | 7 Participants | 14 Participants | 1 Participants | 0 Participants | 6 Participants |
| Disease Stage IV | 4 Participants | 9 Participants | 0 Participants | 2 Participants | 3 Participants |
| ECOG PS 0 | 9 Participants | 19 Participants | 1 Participants | 2 Participants | 7 Participants |
| ECOG PS 1 | 2 Participants | 4 Participants | 0 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 22 Participants | 1 Participants | 2 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Histology Cutaneous melanoma | 10 Participants | 21 Participants | 1 Participants | 2 Participants | 8 Participants |
| Histology Subungual melanoma | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Histology Unknown melanoma primary | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Prior Therapy Chemotherapy multiple agent | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Prior Therapy Granulocyte-macrophage colony stimulating factor | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants |
| Prior Therapy Interferon alpha-2b | 7 participants | 14 participants | 1 participants | 1 participants | 5 participants |
| Prior Therapy No prior therapy | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants |
| Prior Therapy Radiation therapy | 1 participants | 3 participants | 0 participants | 0 participants | 2 participants |
| Prior Therapy Surgery | 10 participants | 22 participants | 1 participants | 2 participants | 9 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 22 Participants | 1 Participants | 2 Participants | 9 Participants |
| Region of Enrollment United States | 11 participants | 23 participants | 1 participants | 2 participants | 9 participants |
| Sex: Female, Male Female | 5 Participants | 8 Participants | 0 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 6 Participants | 15 Participants | 1 Participants | 1 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 11 | 5 / 9 | 1 / 2 | 1 / 1 |
| other Total, other adverse events | 10 / 11 | 7 / 9 | 2 / 2 | 1 / 1 |
| serious Total, serious adverse events | 2 / 11 | 2 / 9 | 0 / 2 | 1 / 1 |
Outcome results
Primary
Ganglioside Expressed by Tumor Cells (GD2)
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).
Time frame: up to 1 week
Population: There were 12 participants with evaluable tumor samples for GD2 analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A | Ganglioside Expressed by Tumor Cells (GD2) | Positive GD2 | 3 Participants |
| Group A | Ganglioside Expressed by Tumor Cells (GD2) | Negative GD2 | 3 Participants |
| Group B | Ganglioside Expressed by Tumor Cells (GD2) | Positive GD2 | 3 Participants |
| Group B | Ganglioside Expressed by Tumor Cells (GD2) | Negative GD2 | 3 Participants |
Primary
Overall Survival (OS)
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.
Time frame: up to 24 months
Population: There was no intent in the protocol to compare OS between Groups A and B.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A | Overall Survival (OS) | 61.57 months |
Primary
Recurrence Free Survival (RFS)
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.
Time frame: up to 24 months
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A | Recurrence Free Survival (RFS) | 5.73 months |
Secondary
Anti-Fc-IL2 Antibodies
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
Time frame: up to 12 weeks
Population: 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).
Secondary
Anti-Idiotypic Antibodies
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.
Time frame: up to 12 weeks
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Anti-Idiotypic Antibodies | Cycle 1 Day 1 pre-treatment | 0.2 Optical Density (OD) | Standard Error 0.09 |
| Group A | Anti-Idiotypic Antibodies | Cycle 1 Day 4 | 0.4 Optical Density (OD) | Standard Error 0.11 |
| Group A | Anti-Idiotypic Antibodies | Cycle 1 Day 8 | 1.5 Optical Density (OD) | Standard Error 0.23 |
| Group A | Anti-Idiotypic Antibodies | End Cycle 1 | 0.6 Optical Density (OD) | Standard Error 0.24 |
| Group A | Anti-Idiotypic Antibodies | Cycle 2 Day 1 pre-treatment | 0.4 Optical Density (OD) | Standard Error 0.11 |
| Group A | Anti-Idiotypic Antibodies | Cycle 2 Day 4 | 0.4 Optical Density (OD) | Standard Error 0.16 |
| Group A | Anti-Idiotypic Antibodies | Cycle 2 Day 8 | 1.5 Optical Density (OD) | Standard Error 0.31 |
| Group A | Anti-Idiotypic Antibodies | End Cycle 2 | 0.9 Optical Density (OD) | Standard Error 0.24 |
| Group A | Anti-Idiotypic Antibodies | Cycle 3 Day 1 pre-treatment | 0.9 Optical Density (OD) | Standard Error 0.28 |
| Group A | Anti-Idiotypic Antibodies | Cycle 3 Day 4 | 0.4 Optical Density (OD) | Standard Error 0.09 |
| Group A | Anti-Idiotypic Antibodies | Cycle 3 Day 8 | 1.0 Optical Density (OD) | Standard Error 0.3 |
| Group A | Anti-Idiotypic Antibodies | End Cycle 3 | 0.7 Optical Density (OD) | Standard Error 0.27 |
| Group B | Anti-Idiotypic Antibodies | Cycle 3 Day 8 | 1.2 Optical Density (OD) | Standard Error 0.28 |
| Group B | Anti-Idiotypic Antibodies | Cycle 1 Day 1 pre-treatment | 0.2 Optical Density (OD) | Standard Error 0.12 |
| Group B | Anti-Idiotypic Antibodies | Cycle 2 Day 8 | 1.4 Optical Density (OD) | Standard Error 0.23 |
| Group B | Anti-Idiotypic Antibodies | Cycle 1 Day 4 | 0.8 Optical Density (OD) | Standard Error 0.33 |
| Group B | Anti-Idiotypic Antibodies | Cycle 3 Day 4 | 0.6 Optical Density (OD) | Standard Error 0.16 |
| Group B | Anti-Idiotypic Antibodies | Cycle 1 Day 8 | 1.7 Optical Density (OD) | Standard Error 0.42 |
| Group B | Anti-Idiotypic Antibodies | End Cycle 2 | 0.6 Optical Density (OD) | Standard Error 0.16 |
| Group B | Anti-Idiotypic Antibodies | End Cycle 1 | 0.6 Optical Density (OD) | Standard Error 0.18 |
| Group B | Anti-Idiotypic Antibodies | End Cycle 3 | 0.5 Optical Density (OD) | Standard Error 0.12 |
| Group B | Anti-Idiotypic Antibodies | Cycle 2 Day 1 pre-treatment | 0.5 Optical Density (OD) | Standard Error 0.13 |
| Group B | Anti-Idiotypic Antibodies | Cycle 3 Day 1 pre-treatment | 0.5 Optical Density (OD) | Standard Error 0.14 |
| Group B | Anti-Idiotypic Antibodies | Cycle 2 Day 4 | 0.5 Optical Density (OD) | Standard Error 0.17 |
Secondary
C-Reactive Protein (CRP)
CRP measured at baseline, cycle 1 day 3, and cycle 2 day 1.
Time frame: up to 29 days
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group A | C-Reactive Protein (CRP) | baseline | 0 mg/dL |
| Group A | C-Reactive Protein (CRP) | cycle 1 day 3 | 9 mg/dL |
| Group A | C-Reactive Protein (CRP) | cycle 2 day 1 | 0 mg/dL |
| Group B | C-Reactive Protein (CRP) | baseline | 0 mg/dL |
| Group B | C-Reactive Protein (CRP) | cycle 1 day 3 | 11 mg/dL |
| Group B | C-Reactive Protein (CRP) | cycle 2 day 1 | 0 mg/dL |
Secondary
In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels
Soluble 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.
Time frame: up to 12 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 1 End | 2010.8 ng/ml | Standard Error 187.7 |
| Group A | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 2 Day 8 | 6481.0 ng/ml | Standard Error 769.5 |
| Group A | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 1 Day 3 | 6669.0 ng/ml | Standard Error 913.8 |
| Group A | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 2 End | 2065.9 ng/ml | Standard Error 200.3 |
| Group A | 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 |
| Group A | 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 |
| Group A | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 1 Day 8 | 5913.8 ng/ml | Standard Error 614.8 |
| Group A | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 3 Day 3 | 9515.1 ng/ml | Standard Error 1760.6 |
| Group A | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 2 Day 3 | 7643.6 ng/ml | Standard Error 1037.8 |
| Group A | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 3 Day 4 | 13907.1 ng/ml | Standard Error 2319.7 |
| Group A | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 1 Day 4 | 10837.5 ng/ml | Standard Error 1299.4 |
| Group A | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 3 Day 8 | 6705.8 ng/ml | Standard Error 802 |
| Group A | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 2 Day 4 | 12439.5 ng/ml | Standard Error 1670.7 |
| Group A | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 3 End | 2334.8 ng/ml | Standard Error 289.8 |
| Group A | 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 |
| Group B | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 3 End | 2198.8 ng/ml | Standard Error 321.5 |
| Group B | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | 10 min prior to initiation of Cycle 1 treatment | 1229.7 ng/ml | Standard Error 260.8 |
| Group B | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 1 Day 3 | 6285.8 ng/ml | Standard Error 598.2 |
| Group B | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 1 Day 4 | 7378.5 ng/ml | Standard Error 770.8 |
| Group B | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 1 Day 8 | 4405.0 ng/ml | Standard Error 639.8 |
| Group B | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 1 End | 1723.0 ng/ml | Standard Error 127.9 |
| Group B | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | 10 min prior to initiation of Cycle 2 treatment | 1547.1 ng/ml | Standard Error 196.82 |
| Group B | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 2 Day 3 | 7017.7 ng/ml | Standard Error 694.9 |
| Group B | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 2 Day 4 | 11101.1 ng/ml | Standard Error 1168.9 |
| Group B | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 2 Day 8 | 6124.0 ng/ml | Standard Error 772.1 |
| Group B | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 2 End | 1931.7 ng/ml | Standard Error 187.4 |
| Group B | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | 10 min prior to initiation of Cycle 3 | 1901.0 ng/ml | Standard Error 214.3 |
| Group B | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 3 Day 3 | 7636.7 ng/ml | Standard Error 887.3 |
| Group B | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 3 Day 4 | 13029.0 ng/ml | Standard Error 1204.9 |
| Group B | In Vitro Soluble Interleukin-2 (IL2) Receptor Alpha Levels | Cycle 3 Day 8 | 6879.2 ng/ml | Standard Error 506.9 |
Secondary
Lymphocyte Count
Lymphocyte count measured at baseline, cycle 1 day 3, cycle 1 day 8, and cycle 2 day 1
Time frame: up to 29 days
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group A | Lymphocyte Count | baseline | 1750 number of lymphocytes |
| Group A | Lymphocyte Count | cycle 1 day 3 | 200 number of lymphocytes |
| Group A | Lymphocyte Count | cycle 1 day 8 | 4910 number of lymphocytes |
| Group A | Lymphocyte Count | cycle 2 day 1 | 3160 number of lymphocytes |
| Group B | Lymphocyte Count | cycle 2 day 1 | 2100 number of lymphocytes |
| Group B | Lymphocyte Count | baseline | 1440 number of lymphocytes |
| Group B | Lymphocyte Count | cycle 1 day 8 | 3900 number of lymphocytes |
| Group B | Lymphocyte Count | cycle 1 day 3 | 250 number of lymphocytes |
Other Pre-specified
Antibody Dependent Cellular Cytotoxicity (ADCC)
NK 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.
Time frame: up to 12 weeks
Other Pre-specified
Density of Cellular Infiltrate
Time frame: Up to 1 week
Other Pre-specified
Expression of GD2 Target Antigen
Time frame: Up to 1 week
Other Pre-specified
Immunocytokine (IC) Binding
Time frame: up to 1 week
Other Pre-specified
Interferon Gamma (INF-y) Expression
Time frame: Up to 1 week
Other Pre-specified
Natural Killer Cells (NK)
NK 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.
Time frame: up to 12 weeks
Other Pre-specified
T Cell Reactivity
Time frame: Up to 1 week
Other Pre-specified
Tumor Vascularity
Time frame: Up to 1 week