Trial Outcomes & Findings for Vaccine Therapy With or Without Recombinant Interleukin-12 Followed by Daclizumab in Treating Patients With Metastatic Melanoma (NCT NCT01307618)
NCT ID: NCT01307618
Last Updated: 2016-10-24
Results Overview
Data before treatment and after 3 vaccines will be assessed using paired t-tests within each cohort as well as a two-sample t-test of the mean post-treatment levels between cohorts. Repeated measures analysis of variance or mixed effects models will be utilized to further characterize changes in the levels of circulating T cells over time.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
10 participants
Primary outcome timeframe
Up to 4 years
Results posted on
2016-10-24
Participant Flow
Participant milestones
| Measure |
Arm I (Vaccine Therapy)
Patients receive vaccination comprising recombinant MAGE-3.1 antigen, MART-1 antigen, gp100 antigen, and NA17-A2 peptide emulsified with Montanide ISA-51 ID or SC on days 1, 22, and 50.
NA17.A2 Peptide Vaccine: Given SC or ID
Recombinant MAGE-3.1 Antigen: Given SC or ID
MART-1 Antigen: Given SC or ID
Laboratory Biomarker Analysis: Correlative studies
|
Arm II (Vaccine Therapy, IL-12)
Patients receive vaccination as in arm I with an admixture of IL-12 ID or SC on days 1, 22, and 50.
NA17.A2 Peptide Vaccine: Given SC or ID
Recombinant MAGE-3.1 Antigen: Given SC or ID
Recombinant Interleukin-12: Given SC or ID
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|
|
Overall Study
STARTED
|
5
|
5
|
|
Overall Study
COMPLETED
|
5
|
5
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Vaccine Therapy With or Without Recombinant Interleukin-12 Followed by Daclizumab in Treating Patients With Metastatic Melanoma
Baseline characteristics by cohort
| Measure |
Arm I (Vaccine Therapy)
n=5 Participants
Patients receive vaccination comprising recombinant MAGE-3.1 antigen, MART-1 antigen, gp100 antigen, and NA17-A2 peptide emulsified with Montanide ISA-51 ID or SC on days 1, 22, and 50.
NA17.A2 Peptide Vaccine: Given SC or ID
Recombinant MAGE-3.1 Antigen: Given SC or ID
MART-1 Antigen: Given SC or ID
Laboratory Biomarker Analysis: Correlative studies
|
Arm II (Vaccine Therapy, IL-12)
n=5 Participants
Patients receive vaccination as in arm I with an admixture of IL-12 ID or SC on days 1, 22, and 50.
NA17.A2 Peptide Vaccine: Given SC or ID
Recombinant MAGE-3.1 Antigen: Given SC or ID
Recombinant Interleukin-12: Given SC or ID
Laboratory Biomarker Analysis: Correlative studies
|
Total
n=10 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
57.86 years
STANDARD_DEVIATION 12.55 • n=5 Participants
|
66.16 years
STANDARD_DEVIATION 15.11 • n=7 Participants
|
62.01 years
STANDARD_DEVIATION 13.81 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 4 yearsPopulation: Due to lack of clinical efficacy and lack of drug supply, trial was closed early and frequency of vaccine-induced CD8+T cells was not measured.
Data before treatment and after 3 vaccines will be assessed using paired t-tests within each cohort as well as a two-sample t-test of the mean post-treatment levels between cohorts. Repeated measures analysis of variance or mixed effects models will be utilized to further characterize changes in the levels of circulating T cells over time.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Up to 4 yearsPopulation: Due to lack of clinical efficacy and lack of drug supply, trial was closed early and absolute number of CD4+CD25+FoxP3+Regulatory T Cells from peripheral blood was not measured.
Descriptive statistics and paired t-tests will be generated to describe the frequency and absolute number of CD4+CD25+FoxP3+ cells before and after daclizumab, and also at subsequent time points. Repeated measures of analysis of variance and mixed effects models will be used to further evaluate change in numbers over time, and to compare these changes between cohorts.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Up to 4 yearsPopulation: Patients who experienced any adverse event were counted.
Outcome measures
| Measure |
Arm I (Vaccine Therapy)
n=5 Participants
Patients receive vaccination comprising recombinant MAGE-3.1 antigen, MART-1 antigen, gp100 antigen, and NA17-A2 peptide emulsified with Montanide ISA-51 ID or SC on days 1, 22, and 50.
NA17.A2 Peptide Vaccine: Given SC or ID
Recombinant MAGE-3.1 Antigen: Given SC or ID
MART-1 Antigen: Given SC or ID
Laboratory Biomarker Analysis: Correlative studies
|
Arm II (Vaccine Therapy, IL-12)
n=5 Participants
Patients receive vaccination as in arm I with an admixture of IL-12 ID or SC on days 1, 22, and 50.
NA17.A2 Peptide Vaccine: Given SC or ID
Recombinant MAGE-3.1 Antigen: Given SC or ID
Recombinant Interleukin-12: Given SC or ID
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Erythema multiforme (Grade 1)
|
1 participants
|
0 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Fatigue (Grade 1)
|
3 participants
|
2 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Hypophosphatemia (Grade 1)
|
0 participants
|
1 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Pain (Grade 1)
|
0 participants
|
1 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Abdominal pain (Grade 1)
|
1 participants
|
0 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Anxiety (Grade 1)
|
1 participants
|
1 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Chills (Grade 1)
|
1 participants
|
0 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Cough (Grade 1)
|
1 participants
|
1 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Diarrhea (Grade 1)
|
1 participants
|
0 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Dyspnea (Grade 1)
|
1 participants
|
0 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Infections (Grade 1)
|
1 participants
|
0 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Injection site reaction (Grade 1)
|
4 participants
|
2 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Pruritus (Grade 1)
|
1 participants
|
0 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Rectal hemorrhage (Grade1 )
|
1 participants
|
0 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Rectal pain (Grade 1)
|
1 participants
|
0 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Arthralgia (Grade 1)
|
0 participants
|
1 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Bone pain (Grade 1)
|
0 participants
|
1 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Death NOS (Grade 5)
|
0 participants
|
1 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Dehydration (Grade 1)
|
0 participants
|
1 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Dyspnea (Grade 2)
|
0 participants
|
1 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Headache (Grade 1)
|
0 participants
|
1 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Hypoalbuminemia (Grade 1)
|
0 participants
|
1 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Pleuritic pain (Grade 1)
|
0 participants
|
1 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Proteinuria (Grade 1)
|
0 participants
|
1 participants
|
|
Type and Grade of Toxicity Incidents Assessed by Common Toxicity Criteria Version 4.0 (CTCAE v4.0)
Psychiatric disorders (Grade 2)
|
0 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Up to 4 yearsMedian progression-free survival and the associated 95% confidence limits will be derived using the procedure described in Brookmeyer and Crowley. The criteria for progressive disease are 1) appearance of new lesions, 2) 25% increase in the sum of the product of the largest perpendicular diameters of the indicator lesions, or 3) reappearance of any tumor.
Outcome measures
| Measure |
Arm I (Vaccine Therapy)
n=5 Participants
Patients receive vaccination comprising recombinant MAGE-3.1 antigen, MART-1 antigen, gp100 antigen, and NA17-A2 peptide emulsified with Montanide ISA-51 ID or SC on days 1, 22, and 50.
NA17.A2 Peptide Vaccine: Given SC or ID
Recombinant MAGE-3.1 Antigen: Given SC or ID
MART-1 Antigen: Given SC or ID
Laboratory Biomarker Analysis: Correlative studies
|
Arm II (Vaccine Therapy, IL-12)
n=5 Participants
Patients receive vaccination as in arm I with an admixture of IL-12 ID or SC on days 1, 22, and 50.
NA17.A2 Peptide Vaccine: Given SC or ID
Recombinant MAGE-3.1 Antigen: Given SC or ID
Recombinant Interleukin-12: Given SC or ID
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|
|
Progression-free Survival Assessed by Modified World Health Organization (WHO) Criteria
|
130 days
Interval 77.0 to
The upper limit of the 95% confidence interval was not reached.
|
64 days
Interval 63.0 to
The upper limit of the 95% confidence interval was not reached.
|
SECONDARY outcome
Timeframe: Up to 4 yearsMedian overall survival and the associated 95% confidence limits will be derived using the procedure described in Brookmeyer and Crowley.
Outcome measures
| Measure |
Arm I (Vaccine Therapy)
n=5 Participants
Patients receive vaccination comprising recombinant MAGE-3.1 antigen, MART-1 antigen, gp100 antigen, and NA17-A2 peptide emulsified with Montanide ISA-51 ID or SC on days 1, 22, and 50.
NA17.A2 Peptide Vaccine: Given SC or ID
Recombinant MAGE-3.1 Antigen: Given SC or ID
MART-1 Antigen: Given SC or ID
Laboratory Biomarker Analysis: Correlative studies
|
Arm II (Vaccine Therapy, IL-12)
n=5 Participants
Patients receive vaccination as in arm I with an admixture of IL-12 ID or SC on days 1, 22, and 50.
NA17.A2 Peptide Vaccine: Given SC or ID
Recombinant MAGE-3.1 Antigen: Given SC or ID
Recombinant Interleukin-12: Given SC or ID
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|
|
Overall Survival Assessed by Modified WHO Criteria
|
804 days
The 95% confidence interval was not reached. Only one patient died and others were censored.
|
199 days
Interval 92.0 to
The upper limit of 95% confidence interval was not reached.
|
SECONDARY outcome
Timeframe: Up to 4 yearsPopulation: Due to lack of clinical efficacy and lack of drug supply, trial was closed early and gene expression profiles was not measured.
Gene cluster analysis will be performed using deoxyribonucleic acid (DNA)-Chip Analyzer (dCHIP) software and comparisons will be made before and after treatment in each individual patient, and between responders and non-responders. Attempts will be made to identify gene expression profiles that correlate with clinical outcome.
Outcome measures
Outcome data not reported
Adverse Events
Arm I (Vaccine Therapy)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Arm II (Vaccine Therapy, IL-12)
Serious events: 2 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Arm I (Vaccine Therapy)
n=5 participants at risk
Patients receive vaccination comprising recombinant MAGE-3.1 antigen, MART-1 antigen, gp100 antigen, and NA17-A2 peptide emulsified with Montanide ISA-51 ID or SC on days 1, 22, and 50.
NA17.A2 Peptide Vaccine: Given SC or ID
Recombinant MAGE-3.1 Antigen: Given SC or ID
MART-1 Antigen: Given SC or ID
Laboratory Biomarker Analysis: Correlative studies
|
Arm II (Vaccine Therapy, IL-12)
n=5 participants at risk
Patients receive vaccination as in arm I with an admixture of IL-12 ID or SC on days 1, 22, and 50.
NA17.A2 Peptide Vaccine: Given SC or ID
Recombinant MAGE-3.1 Antigen: Given SC or ID
Recombinant Interleukin-12: Given SC or ID
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/5
|
20.0%
1/5
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/5
|
20.0%
1/5
|
|
Psychiatric disorders
Psychiatric disorders - Other, specify
|
0.00%
0/5
|
20.0%
1/5
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/5
|
20.0%
1/5
|
|
General disorders
Death NOS
|
0.00%
0/5
|
20.0%
1/5
|
Other adverse events
| Measure |
Arm I (Vaccine Therapy)
n=5 participants at risk
Patients receive vaccination comprising recombinant MAGE-3.1 antigen, MART-1 antigen, gp100 antigen, and NA17-A2 peptide emulsified with Montanide ISA-51 ID or SC on days 1, 22, and 50.
NA17.A2 Peptide Vaccine: Given SC or ID
Recombinant MAGE-3.1 Antigen: Given SC or ID
MART-1 Antigen: Given SC or ID
Laboratory Biomarker Analysis: Correlative studies
|
Arm II (Vaccine Therapy, IL-12)
n=5 participants at risk
Patients receive vaccination as in arm I with an admixture of IL-12 ID or SC on days 1, 22, and 50.
NA17.A2 Peptide Vaccine: Given SC or ID
Recombinant MAGE-3.1 Antigen: Given SC or ID
Recombinant Interleukin-12: Given SC or ID
Laboratory Biomarker Analysis: Correlative studies
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
20.0%
1/5
|
0.00%
0/5
|
|
Psychiatric disorders
Anxiety
|
20.0%
1/5
|
20.0%
1/5
|
|
General disorders
Chills
|
20.0%
1/5
|
0.00%
0/5
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.0%
1/5
|
20.0%
1/5
|
|
Gastrointestinal disorders
Diarrhea
|
20.0%
1/5
|
0.00%
0/5
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
20.0%
1/5
|
0.00%
0/5
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
20.0%
1/5
|
0.00%
0/5
|
|
General disorders
Fatigue
|
60.0%
3/5
|
60.0%
3/5
|
|
Infections and infestations
Infections and infestations - Other, specify
|
20.0%
1/5
|
0.00%
0/5
|
|
General disorders
Injection site reaction
|
80.0%
4/5
|
20.0%
1/5
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
20.0%
1/5
|
0.00%
0/5
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
20.0%
1/5
|
0.00%
0/5
|
|
Gastrointestinal disorders
Rectal pain
|
20.0%
1/5
|
0.00%
0/5
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/5
|
20.0%
1/5
|
|
Nervous system disorders
Headache
|
0.00%
0/5
|
20.0%
1/5
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
0.00%
0/5
|
20.0%
1/5
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.00%
0/5
|
20.0%
1/5
|
|
General disorders
Pain
|
0.00%
0/5
|
20.0%
1/5
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
0.00%
0/5
|
20.0%
1/5
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/5
|
20.0%
1/5
|
Additional Information
Tomas Gajewski
University of Chicago Comprehensive Cancer Center
Phone: 773-702-4601
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60