Trial Outcomes & Findings for Vaccine Therapy With or Without Cyclophosphamide in Treating Patients Who Have Undergone Surgery for Stage II, Stage III, or Stage IV Melanoma (NCT NCT00118274)
NCT ID: NCT00118274
Last Updated: 2021-04-20
Results Overview
Number of participants with dose-limiting toxicities
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
170 participants
Primary outcome timeframe
30 days after receiving the last dose of study drug, up to week 52
Results posted on
2021-04-20
Participant Flow
Participant milestones
| Measure |
Arm I
Patients receive vaccine comprising multi-epitope melanoma peptides, tetanus toxoid helper peptide emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
incomplete Freund's adjuvant: Given intradermally and subcutaneously
multi-epitope melanoma peptide vaccine: Given intradermally and subcutaneously
tetanus toxoid helper peptide: Given intradermally and subcutaneously
|
Arm II
Patients receive cyclophosphamide IV over 30-60 minutes on day -4. Patients then receive vaccine comprising multi-epitope melanoma peptides, tetanus toxoid helper peptide emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
incomplete Freund's adjuvant: Given intradermally and subcutaneously
multi-epitope melanoma peptide vaccine: Given intradermally and subcutaneously
tetanus toxoid helper peptide: Given intradermally and subcutaneously
cyclophosphamide: Given IV
|
Arm III
Patients receive vaccine comprising melanoma peptides and multi-epitope melanoma helper peptides emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
incomplete Freund's adjuvant: Given intradermally and subcutaneously
melanoma helper peptide vaccine: Given intradermally and subcutaneously
multi-epitope melanoma peptide vaccine: Given intradermally and subcutaneously
|
Arm IV
Patients receive cyclophosphamide IV over 30-60 minutes on day -4. Patients then receive vaccine comprising melanoma peptides and multi-epitope melanoma helper peptides emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
incomplete Freund's adjuvant: Given intradermally and subcutaneously
melanoma helper peptide vaccine: Given intradermally and subcutaneously
multi-epitope melanoma peptide vaccine: Given intradermally and subcutaneously
cyclophosphamide: Given IV
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
41
|
43
|
42
|
44
|
|
Overall Study
COMPLETED
|
21
|
21
|
25
|
29
|
|
Overall Study
NOT COMPLETED
|
20
|
22
|
17
|
15
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Vaccine Therapy With or Without Cyclophosphamide in Treating Patients Who Have Undergone Surgery for Stage II, Stage III, or Stage IV Melanoma
Baseline characteristics by cohort
| Measure |
Arm I
n=41 Participants
Patients receive vaccine comprising multi-epitope melanoma peptides, tetanus toxoid helper peptide emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
incomplete Freund's adjuvant: Given intradermally and subcutaneously
multi-epitope melanoma peptide vaccine: Given intradermally and subcutaneously
tetanus toxoid helper peptide: Given intradermally and subcutaneously
|
Arm II
n=43 Participants
Patients receive cyclophosphamide IV over 30-60 minutes on day -4. Patients then receive vaccine comprising multi-epitope melanoma peptides, tetanus toxoid helper peptide emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
incomplete Freund's adjuvant: Given intradermally and subcutaneously
multi-epitope melanoma peptide vaccine: Given intradermally and subcutaneously
tetanus toxoid helper peptide: Given intradermally and subcutaneously
cyclophosphamide: Given IV
|
Arm III
n=42 Participants
Patients receive vaccine comprising melanoma peptides and multi-epitope melanoma helper peptides emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
incomplete Freund's adjuvant: Given intradermally and subcutaneously
melanoma helper peptide vaccine: Given intradermally and subcutaneously
multi-epitope melanoma peptide vaccine: Given intradermally and subcutaneously
|
Arm IV
n=44 Participants
Patients receive cyclophosphamide IV over 30-60 minutes on day -4. Patients then receive vaccine comprising melanoma peptides and multi-epitope melanoma helper peptides emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
incomplete Freund's adjuvant: Given intradermally and subcutaneously
melanoma helper peptide vaccine: Given intradermally and subcutaneously
multi-epitope melanoma peptide vaccine: Given intradermally and subcutaneously
cyclophosphamide: Given IV
|
Total
n=170 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
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
|
|
Age, Categorical
Between 18 and 65 years
|
30 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
32 Participants
n=4 Participants
|
125 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
11 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
45 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
56 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
31 Participants
n=4 Participants
|
114 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 30 days after receiving the last dose of study drug, up to week 52Population: Intent to treat population including 167 eligible and 3 ineligible.
Number of participants with dose-limiting toxicities
Outcome measures
| Measure |
Arm I
n=41 Participants
Patients receive vaccine comprising multi-epitope melanoma peptides, tetanus toxoid helper peptide emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
incomplete Freund's adjuvant: Given intradermally and subcutaneously
multi-epitope melanoma peptide vaccine: Given intradermally and subcutaneously
tetanus toxoid helper peptide: Given intradermally and subcutaneously
|
Arm II
n=43 Participants
Patients receive cyclophosphamide IV over 30-60 minutes on day -4. Patients then receive vaccine comprising multi-epitope melanoma peptides, tetanus toxoid helper peptide emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
incomplete Freund's adjuvant: Given intradermally and subcutaneously
multi-epitope melanoma peptide vaccine: Given intradermally and subcutaneously
tetanus toxoid helper peptide: Given intradermally and subcutaneously
cyclophosphamide: Given IV
|
Arm III
n=42 Participants
Patients receive vaccine comprising melanoma peptides and multi-epitope melanoma helper peptides emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
incomplete Freund's adjuvant: Given intradermally and subcutaneously
melanoma helper peptide vaccine: Given intradermally and subcutaneously
multi-epitope melanoma peptide vaccine: Given intradermally and subcutaneously
|
Arm IV
n=44 Participants
Patients receive cyclophosphamide IV over 30-60 minutes on day -4. Patients then receive vaccine comprising melanoma peptides and multi-epitope melanoma helper peptides emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
incomplete Freund's adjuvant: Given intradermally and subcutaneously
melanoma helper peptide vaccine: Given intradermally and subcutaneously
multi-epitope melanoma peptide vaccine: Given intradermally and subcutaneously
cyclophosphamide: Given IV
|
|---|---|---|---|---|
|
Safety of the Peptide Vaccines
|
4 Participants
|
7 Participants
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: 50 daysPopulation: All eligible participants, total = 167.
The primary end point was the maximum cumulative circulating CD8+ T cell response to 12 melanoma peptides (12MP) measured by ELISpot assay over the first six vaccines (to day 50).
Outcome measures
| Measure |
Arm I
n=41 Participants
Patients receive vaccine comprising multi-epitope melanoma peptides, tetanus toxoid helper peptide emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
incomplete Freund's adjuvant: Given intradermally and subcutaneously
multi-epitope melanoma peptide vaccine: Given intradermally and subcutaneously
tetanus toxoid helper peptide: Given intradermally and subcutaneously
|
Arm II
n=41 Participants
Patients receive cyclophosphamide IV over 30-60 minutes on day -4. Patients then receive vaccine comprising multi-epitope melanoma peptides, tetanus toxoid helper peptide emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
incomplete Freund's adjuvant: Given intradermally and subcutaneously
multi-epitope melanoma peptide vaccine: Given intradermally and subcutaneously
tetanus toxoid helper peptide: Given intradermally and subcutaneously
cyclophosphamide: Given IV
|
Arm III
n=42 Participants
Patients receive vaccine comprising melanoma peptides and multi-epitope melanoma helper peptides emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
incomplete Freund's adjuvant: Given intradermally and subcutaneously
melanoma helper peptide vaccine: Given intradermally and subcutaneously
multi-epitope melanoma peptide vaccine: Given intradermally and subcutaneously
|
Arm IV
n=43 Participants
Patients receive cyclophosphamide IV over 30-60 minutes on day -4. Patients then receive vaccine comprising melanoma peptides and multi-epitope melanoma helper peptides emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
incomplete Freund's adjuvant: Given intradermally and subcutaneously
melanoma helper peptide vaccine: Given intradermally and subcutaneously
multi-epitope melanoma peptide vaccine: Given intradermally and subcutaneously
cyclophosphamide: Given IV
|
|---|---|---|---|---|
|
Immunogenicity (CD8+ T Cell Response to 12 Melanoma Peptides, 12MP) as Measured by Elispot Assay, up to Day 50
|
32 Participants
|
29 Participants
|
8 Participants
|
12 Participants
|
Adverse Events
Arm I
Serious events: 0 serious events
Other events: 41 other events
Deaths: 0 deaths
Arm II
Serious events: 0 serious events
Other events: 43 other events
Deaths: 0 deaths
Arm III
Serious events: 0 serious events
Other events: 41 other events
Deaths: 0 deaths
Arm IV
Serious events: 0 serious events
Other events: 44 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Arm I
n=41 participants at risk
Patients receive vaccine comprising multi-epitope melanoma peptides, tetanus toxoid helper peptide emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
incomplete Freund's adjuvant: Given intradermally and subcutaneously
multi-epitope melanoma peptide vaccine: Given intradermally and subcutaneously
tetanus toxoid helper peptide: Given intradermally and subcutaneously
|
Arm II
n=43 participants at risk
Patients receive cyclophosphamide IV over 30-60 minutes on day -4. Patients then receive vaccine comprising multi-epitope melanoma peptides, tetanus toxoid helper peptide emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
incomplete Freund's adjuvant: Given intradermally and subcutaneously
multi-epitope melanoma peptide vaccine: Given intradermally and subcutaneously
tetanus toxoid helper peptide: Given intradermally and subcutaneously
cyclophosphamide: Given IV
|
Arm III
n=42 participants at risk
Patients receive vaccine comprising melanoma peptides and multi-epitope melanoma helper peptides emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
incomplete Freund's adjuvant: Given intradermally and subcutaneously
melanoma helper peptide vaccine: Given intradermally and subcutaneously
multi-epitope melanoma peptide vaccine: Given intradermally and subcutaneously
|
Arm IV
n=44 participants at risk
Patients receive cyclophosphamide IV over 30-60 minutes on day -4. Patients then receive vaccine comprising melanoma peptides and multi-epitope melanoma helper peptides emulsified in Montanide ISA-51 intradermally and subcutaneously on days 1, 8, 15, 29, 36, 43, 85, 183, 274, and 365.
incomplete Freund's adjuvant: Given intradermally and subcutaneously
melanoma helper peptide vaccine: Given intradermally and subcutaneously
multi-epitope melanoma peptide vaccine: Given intradermally and subcutaneously
cyclophosphamide: Given IV
|
|---|---|---|---|---|
|
Immune system disorders
Autoimmune reaction
|
0.00%
0/41
|
11.6%
5/43
|
7.1%
3/42
|
4.5%
2/44
|
|
Immune system disorders
Rhinitis
|
19.5%
8/41
|
32.6%
14/43
|
33.3%
14/42
|
13.6%
6/44
|
|
Blood and lymphatic system disorders
Hemoglobin
|
43.9%
18/41
|
34.9%
15/43
|
19.0%
8/42
|
36.4%
16/44
|
|
Blood and lymphatic system disorders
Leukocytes
|
19.5%
8/41
|
14.0%
6/43
|
11.9%
5/42
|
25.0%
11/44
|
|
Blood and lymphatic system disorders
Lymphopenia
|
22.0%
9/41
|
18.6%
8/43
|
9.5%
4/42
|
15.9%
7/44
|
|
Blood and lymphatic system disorders
neutrophils
|
4.9%
2/41
|
9.3%
4/43
|
9.5%
4/42
|
4.5%
2/44
|
|
Blood and lymphatic system disorders
platelets
|
2.4%
1/41
|
0.00%
0/43
|
7.1%
3/42
|
2.3%
1/44
|
|
General disorders
Fatigue
|
53.7%
22/41
|
88.4%
38/43
|
66.7%
28/42
|
68.2%
30/44
|
|
General disorders
Fever
|
36.6%
15/41
|
65.1%
28/43
|
33.3%
14/42
|
31.8%
14/44
|
|
General disorders
Rigors/chills
|
63.4%
26/41
|
76.7%
33/43
|
40.5%
17/42
|
40.9%
18/44
|
|
General disorders
Sweating
|
39.0%
16/41
|
58.1%
25/43
|
38.1%
16/42
|
36.4%
16/44
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/41
|
4.7%
2/43
|
9.5%
4/42
|
4.5%
2/44
|
|
Skin and subcutaneous tissue disorders
Flushing
|
19.5%
8/41
|
20.9%
9/43
|
23.8%
10/42
|
13.6%
6/44
|
|
Skin and subcutaneous tissue disorders
hypopigmentation
|
7.3%
3/41
|
2.3%
1/43
|
4.8%
2/42
|
4.5%
2/44
|
|
Skin and subcutaneous tissue disorders
injection site reaction
|
97.6%
40/41
|
100.0%
43/43
|
90.5%
38/42
|
97.7%
43/44
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
12.2%
5/41
|
18.6%
8/43
|
14.3%
6/42
|
18.2%
8/44
|
|
Skin and subcutaneous tissue disorders
Rash
|
22.0%
9/41
|
30.2%
13/43
|
14.3%
6/42
|
15.9%
7/44
|
|
Skin and subcutaneous tissue disorders
Ulceration
|
29.3%
12/41
|
44.2%
19/43
|
7.1%
3/42
|
22.7%
10/44
|
|
Gastrointestinal disorders
Anorexia
|
34.1%
14/41
|
51.2%
22/43
|
33.3%
14/42
|
27.3%
12/44
|
|
Gastrointestinal disorders
Constipation
|
2.4%
1/41
|
9.3%
4/43
|
4.8%
2/42
|
11.4%
5/44
|
|
Gastrointestinal disorders
Diarrhea
|
31.7%
13/41
|
30.2%
13/43
|
26.2%
11/42
|
25.0%
11/44
|
|
Gastrointestinal disorders
Mucositis (clinical exam) - Oral cavity
|
17.1%
7/41
|
14.0%
6/43
|
11.9%
5/42
|
6.8%
3/44
|
|
Gastrointestinal disorders
Nausea
|
41.5%
17/41
|
55.8%
24/43
|
35.7%
15/42
|
56.8%
25/44
|
|
Gastrointestinal disorders
Vomiting
|
12.2%
5/41
|
23.3%
10/43
|
4.8%
2/42
|
15.9%
7/44
|
|
Blood and lymphatic system disorders
Edema: limb
|
4.9%
2/41
|
7.0%
3/43
|
9.5%
4/42
|
0.00%
0/44
|
|
Hepatobiliary disorders
ALT
|
2.4%
1/41
|
0.00%
0/43
|
2.4%
1/42
|
6.8%
3/44
|
|
Hepatobiliary disorders
AST
|
9.8%
4/41
|
4.7%
2/43
|
9.5%
4/42
|
9.1%
4/44
|
|
Hepatobiliary disorders
Bilirubin
|
4.9%
2/41
|
7.0%
3/43
|
9.5%
4/42
|
4.5%
2/44
|
|
Investigations
Hypercalcemia
|
0.00%
0/41
|
0.00%
0/43
|
7.1%
3/42
|
2.3%
1/44
|
|
Investigations
Hyperglycemia
|
24.4%
10/41
|
48.8%
21/43
|
28.6%
12/42
|
36.4%
16/44
|
|
Investigations
Hyperkalemia
|
22.0%
9/41
|
20.9%
9/43
|
16.7%
7/42
|
13.6%
6/44
|
|
Investigations
Hypocalcemia
|
0.00%
0/41
|
7.0%
3/43
|
0.00%
0/42
|
0.00%
0/44
|
|
Investigations
Hypoglycemia
|
4.9%
2/41
|
7.0%
3/43
|
9.5%
4/42
|
11.4%
5/44
|
|
Investigations
Hypokalemia
|
2.4%
1/41
|
7.0%
3/43
|
0.00%
0/42
|
6.8%
3/44
|
|
Investigations
Hyponatremia
|
2.4%
1/41
|
9.3%
4/43
|
2.4%
1/42
|
9.1%
4/44
|
|
Nervous system disorders
Dizziness
|
29.3%
12/41
|
25.6%
11/43
|
19.0%
8/42
|
20.5%
9/44
|
|
Psychiatric disorders
Mood alteration - agitation
|
4.9%
2/41
|
0.00%
0/43
|
7.1%
3/42
|
9.1%
4/44
|
|
Psychiatric disorders
Mood alteration - anxiety
|
4.9%
2/41
|
4.7%
2/43
|
7.1%
3/42
|
0.00%
0/44
|
|
Psychiatric disorders
Mood alteration - depression
|
7.3%
3/41
|
4.7%
2/43
|
2.4%
1/42
|
2.3%
1/44
|
|
Musculoskeletal and connective tissue disorders
Pain - extremity - limb
|
0.00%
0/41
|
7.0%
3/43
|
4.8%
2/42
|
0.00%
0/44
|
|
General disorders
Pain - headache
|
58.5%
24/41
|
58.1%
25/43
|
50.0%
21/42
|
36.4%
16/44
|
|
Musculoskeletal and connective tissue disorders
Pain - joint
|
39.0%
16/41
|
32.6%
14/43
|
28.6%
12/42
|
31.8%
14/44
|
|
Musculoskeletal and connective tissue disorders
Pain - muscle
|
51.2%
21/41
|
51.2%
22/43
|
28.6%
12/42
|
27.3%
12/44
|
|
Musculoskeletal and connective tissue disorders
Pain - other
|
0.00%
0/41
|
7.0%
3/43
|
0.00%
0/42
|
9.1%
4/44
|
|
Respiratory, thoracic and mediastinal disorders
Pain - throat/pharynx/larynx
|
19.5%
8/41
|
11.6%
5/43
|
21.4%
9/42
|
22.7%
10/44
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
36.6%
15/41
|
32.6%
14/43
|
35.7%
15/42
|
22.7%
10/44
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
29.3%
12/41
|
25.6%
11/43
|
11.9%
5/42
|
9.1%
4/44
|
|
Respiratory, thoracic and mediastinal disorders
Nasal/paranasal reaction
|
24.4%
10/41
|
32.6%
14/43
|
26.2%
11/42
|
25.0%
11/44
|
|
General disorders
Flu-like syndrome
|
24.4%
10/41
|
30.2%
13/43
|
14.3%
6/42
|
11.4%
5/44
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place