Study of a Multi-Antigen Therapeutic Vaccine in Patients With Metastatic Melanoma
Study Details
Study Description
Brief Summary
Primary objective:
To evaluate the clinical activity of the vaccine regimen, as indicated by progression-free survival versus the clinical activity of the reference treatment.
Secondary objectives:
Safety: To describe the safety profile in both treatment groups.
Efficacy: To determine the objective clinical responses of patients in both treatment groups:
complete response and partial response.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Eligible participants will be randomized to receive either a vaccine treatment consisting of a series of multi-antigen melanoma vaccine and GM-CSF injections, followed by high-dose IFN-α2b or only the high-dose IFN-α2b.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Study Group 1: ALVAC melanoma vaccine Participants will receive a multi-antigen of modified canarypox virus (ALVAC[2]) melanoma vaccine and granulocyte macrophage colony stimulating factor (GM-CSF) every 3 weeks, followed by 4 weeks of high-dose interferon alpha-2b 5 times per week. |
Biological: ALVAC(2) Melanoma multi-antigen therapeutic vaccine
0.5 mL, 2 cycles
|
| Active Comparator: Study Group 2: Interferon alpha-2b Participants on 4 weeks of high-dose interferon alpha-2b 5 times per week. Participants who showed disease progression after Cycle 1 will be permitted to cross over to Group 1 treatment. |
Biological: Intron A, Interferon alpha -2b
0.5 mL, 5 times per week for 4 weeks
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Summary of Disease Progression in Study Participants, Intent-to-treat Population [Day 0 up to 35 weeks post 1st vaccination or treatment]
Number of evaluable study participants who had died or experienced objective disease progression (no clinical objective response to treatment as evaluated by computed tomography [CT] scans or physical examination).
- Progression-Free Survival Time by Response Evaluation Criteria in Solid Tumor (RECIST) Criteria in the Intent-to-treat Population [Day 0 - up to 35 weeks post 1st vaccination or treatment]
Progression-Free Survival was assessed by the Response Evaluation Criteria in Solid Tumor criteria from the computed tomography (CT) scans, as per-protocol
Secondary Outcome Measures
- Best Overall Objective Response as Number of Participants Responding in the Intent-to-treat Population [Day 0 to 32 weeks post 1st vaccination or treatment]
Objective response rate (ORR) is the sum of complete response (CR) and partial response (PR) Complete response = Disappearance of all target lesions. Partial response = At least a 30% decrease in the sum of longest diameter of target lesions, taking as reference the baseline sum longest diameter.
- Best Overall Objective Response in the Intent-to-treat Population [Day 0 to 32 weeks post 1st vaccination or treatment]
Objective response rate (ORR) is the sum of complete response (CR) and partial response (PR) Complete response = Disappearance of all target lesions. Partial response = At least a 30% decrease in the sum of longest diameter of target lesions, taking as reference the baseline sum longest diameter.
- Best Overall Objective Response as Mean Duration of Response (Weeks) in the Intent-to-treat Population [Day 0 to 32 weeks post 1st vaccination or treatment]
Objective response rate (ORR) is the sum of complete response (CR) and partial response (PR) Complete response = Disappearance of all target lesions. Partial response = At least a 30% decrease in the sum of longest diameter of target lesions, taking as reference the baseline sum longest diameter.
- Number of Participants Reporting a Grade 3 or Grade 4 Adverse Events by Preferred Term [Day 0 to 12 months post last vaccination]
Common Terminology Criteria for Adverse Events (CTCAE) definitions: Grade 3 is a severe adverse event; Grade 4 is a life-threatening or disabling adverse event.
Other Outcome Measures
- Number of Participants With a Vaccine-Induced Increase of CD8 T-Cell Positive Response by Antigen [Day 0 to 32 weeks post 1st vaccination]
The vaccine-induced increase of CD8 T-Cell positive response by antigen post-vaccination during the observation period compared to the screening values.
- Number of Participants With a Vaccine-Induced Increase of CD4 T-Cell Positive Response by Antigen [Day 0 to 32 weeks post 1st vaccination]
The Vaccine-induced increase of CD4 T-Cell positive response by antigen post-vaccination during the observation period compared to the screening values.
- Summary of Cellular Immune Response to the Vaccination or Treatment (Percent Regulatory T-Cells Responses) [Day 0 to 32 weeks post 1st vaccination or treatment]
The immunogenicity of the treatment regimens was assessed by regulatory T-cell responses as assessed primarily by the multi-parametric intracellular cytokine staining (ICS) assay.
Eligibility Criteria
Criteria
Inclusion Criteria :
-
A pathologically confirmed diagnosis of malignant melanoma with at least one measurable metastatic lesion with a minimum lesion size of 20 mm, based on radiological assessment (or 10 mm if assessed by spiral computed tomography [CT] scan ) as per Response Evaluation Criteria in Solid Tumors (RECIST) criteria (Stages IIIc, IVa, or IVb only, according to the American Joint Committee on Cancer (AJCC) staging system for melanoma). Cutaneous metastasis (assessed by physical examination) must be at least 10 mm. CT scan or magnetic resonance imaging (MRI) is required to rule out brain metastases.
-
Patients who received prior treatment for their metastatic disease must have objective evidence of disease progression.
-
Aged ≥ 18 years on the day of inclusion
-
IRB-approved informed consent form signed
-
Able to attend all scheduled visits and to comply with all trial procedures
-
For a woman, inability to bear a child or negative serum pregnancy test
-
For a woman of child-bearing potential, using an effective method of contraception or abstinence during the study and at least 4 weeks after the last study treatment
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a life expectancy of at least 6 months.
-
Adequate hematologic, hepatic, and renal function (at pre-defined laboratory values).
-
Fully recovered from surgery, if applicable.
Exclusion Criteria :
-
Receipt of two or more previous therapies for metastatic melanoma.
-
Receipt of chemotherapy or another therapy for metastatic melanoma within the last four weeks
-
Receipt of adjuvant interferon therapy within the last six months
-
Concurrent receipt of radiotherapy for the metastatic disease, unless for palliative purposes
-
Participation in another clinical trial within the four weeks preceding the first trial treatment
-
Planned participation in another clinical trial during the present trial period
-
Known Human Immunodeficiency Virus (HIV) infection or hepatitis B (Ag HBs) or hepatitis C seropositivity
-
Presence of active autoimmune disease (excluding vitiligo)
-
Systemic hypersensitivity to bovine products or to any of the vaccine components, including egg products or Neomycin (used to prepare the vaccine), or history of a life-threatening reaction to granulocyte-macrophage colony stimulating factor (GM-CSF) or interferon (IFN)-α2b
-
Current alcohol or drug addiction that may interfere with the ability to comply with trial procedures
-
Significant co-morbid medical conditions, including pre-existing renal disease, cirrhosis, or major depression, which in the estimation of the investigator would preclude safe participation in the study or the accurate interpretation of data.
-
A calculated glomerular filtration rate (GFR) <60 mL/min (based on the Cockroft-Gault formula).
-
Previous receipt of a modified canarypox virus (ALVAC)-based vaccine.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tucson | Arizona | United States | 85724 | |
| 2 | Los Angeles | California | United States | 90024 | |
| 3 | Aurora | Colorado | United States | 80045 | |
| 4 | Atlanta | Georgia | United States | 30322 | |
| 5 | Chicago | Illinois | United States | 60611 | |
| 6 | St Louis | Missouri | United States | 63110 | |
| 7 | Omaha | Nebraska | United States | 68198 | |
| 8 | Lebanon | New Hampshire | United States | 03756 | |
| 9 | Portland | Oregon | United States | 97213 | |
| 10 | Bethlehem | Pennsylvania | United States | 18015 | |
| 11 | Pittsburgh | Pennsylvania | United States | 15232 | |
| 12 | Greenville | South Carolina | United States | 29605 | |
| 13 | Dallas | Texas | United States | 75246 | |
| 14 | San Antonio | Texas | United States | 78229 | |
| 15 | Madison | Wisconsin | United States | 53792 | |
| 16 | Hamilton | Ontario | Canada | L8V 5C2 | |
| 17 | London | Ontario | Canada | ||
| 18 | Toronto | Ontario | Canada | M4N 3M5 | |
| 19 | Montreal | Quebec | Canada | H3A 1A1 |
Sponsors and Collaborators
- Sanofi Pasteur, a Sanofi Company
Investigators
- Study Director: Medical Director, Sanofi Pasteur Inc.
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- MEL11
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled from 20 May 2008 to 31 March 2009 at 8 medical centers in the US and 3 medical centers in Canada. |
|---|---|
| Pre-assignment Detail | A total of 23 participants who met the inclusion and exclusion criteria were enrolled and treated. |
| Arm/Group Title | Study Group 1: ALVAC Melanoma Vaccine | Study Group 2: Interferon Alpha-2b |
|---|---|---|
| Arm/Group Description | Participants received vaccine treatment consisting of 3 series of multi-antigen ALVAC-based melanoma vaccine and GM-CSF injections, followed by four weeks of high-dose IFN-α2b. (Participants that did not show disease progression were allowed a second cycle of treatment) | Participants on Four weeks of high-dose IFN-α2b. (Participants that showed disease progression after Cycle 1 were permitted to cross over to Group 1 treatment) |
| Period Title: Cycle 1 | ||
| STARTED | 11 | 12 |
| COMPLETED | 6 | 4 |
| NOT COMPLETED | 5 | 8 |
| Period Title: Cycle 1 | ||
| STARTED | 11 | 4 |
| COMPLETED | 11 | 4 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Study Group 1: ALVAC Melanoma Vaccine | Study Group 2: Interferon Alpha-2b | Total |
|---|---|---|---|
| Arm/Group Description | Participants received vaccine treatment consisting of 3 series of multi-antigen ALVAC-based melanoma vaccine and GM-CSF injections, followed by four weeks of high-dose IFN-α2b. (Participants that did not show disease progression were allowed a second cycle of treatment) | Participants on Four weeks of high-dose IFN-α2b. (Participants that showed disease progression after Cycle 1 were permitted to cross over to Group 1 treatment) | Total of all reporting groups |
| Overall Participants | 11 | 12 | 23 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
9
81.8%
|
10
83.3%
|
19
82.6%
|
| >=65 years |
2
18.2%
|
2
16.7%
|
4
17.4%
|
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
52.6
(14.23)
|
52.9
(14.34)
|
52.8
(14.3)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
6
54.5%
|
5
41.7%
|
11
47.8%
|
| Male |
5
45.5%
|
7
58.3%
|
12
52.2%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
9
81.8%
|
10
83.3%
|
19
82.6%
|
| Canada |
2
18.2%
|
2
16.7%
|
4
17.4%
|
Outcome Measures
| Title | Number of Participants With a Vaccine-Induced Increase of CD8 T-Cell Positive Response by Antigen |
|---|---|
| Description | The vaccine-induced increase of CD8 T-Cell positive response by antigen post-vaccination during the observation period compared to the screening values. |
| Time Frame | Day 0 to 32 weeks post 1st vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| Immunologic responses were assessed in the Per-protocol evaluable population. |
| Arm/Group Title | Study Group 1: ALVAC Melanoma Vaccine | Study Group 2: Interferon Alpha-2b |
|---|---|---|
| Arm/Group Description | Participants received vaccine treatment consisting of 3 series of multi-antigen ALVAC-based melanoma vaccine and GM-CSF injections, followed by four weeks of high-dose IFN-α2b. (Participants that did not show disease progression were allowed a second cycle of treatment) | Participants on Four weeks of high-dose IFN-α2b. (Participants that showed disease progression after Cycle 1 were permitted to cross over to Group 1 treatment) |
| Measure Participants | 9 | 12 |
| Screening: gp100 pool1 |
0
0%
|
0
0%
|
| Screening: gp100 pool2 |
0
0%
|
0
0%
|
| Screening: gp100 pool3 |
0
0%
|
0
0%
|
| Screening: gp100 pool4 |
0
0%
|
0
0%
|
| Screening: gp100 pool5 |
0
0%
|
0
0%
|
| Screening: gp100 pool6 |
0
0%
|
0
0%
|
| Screening: NYESO-1 pool 1 |
0
0%
|
0
0%
|
| Screening: NYESO-1 pool 2 |
0
0%
|
0
0%
|
| Screening: Mart1 pool |
0
0%
|
0
0%
|
| Screening: Native 15mer pool |
0
0%
|
0
0%
|
| Screening: 9mer pool |
0
0%
|
0
0%
|
| 7 Weeks post 1st Vaccination: gp100 pool1 |
0
0%
|
0
0%
|
| 7 Weeks post 1st Vaccination: gp100 pool2 |
0
0%
|
0
0%
|
| 7 Weeks post 1st Vaccination: gp100 pool3 |
0
0%
|
0
0%
|
| 7 Weeks post 1st Vaccination: gp100 pool4 |
0
0%
|
0
0%
|
| 7 Weeks post 1st Vaccination: gp100 pool5 |
1
9.1%
|
0
0%
|
| 7 Weeks post 1st Vaccination: gp100 pool6 |
0
0%
|
0
0%
|
| 7 Weeks post 1st Vaccination: NYESO-1 pool 1 |
0
0%
|
0
0%
|
| 7 Weeks post 1st Vaccination: NYESO-1 pool 2 |
0
0%
|
0
0%
|
| 7 Weeks post 1st Vaccination: Mart1 pool |
0
0%
|
0
0%
|
| 7 Weeks post 1st Vaccination: Native 15mer pool |
0
0%
|
0
0%
|
| 7 Weeks post 1st Vaccination: 9mer pool |
0
0%
|
0
0%
|
| Title | Number of Participants With a Vaccine-Induced Increase of CD4 T-Cell Positive Response by Antigen |
|---|---|
| Description | The Vaccine-induced increase of CD4 T-Cell positive response by antigen post-vaccination during the observation period compared to the screening values. |
| Time Frame | Day 0 to 32 weeks post 1st vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| Immunologic responses were assessed in the Per-protocol evaluable population. |
| Arm/Group Title | Study Group 1: ALVAC Melanoma Vaccine | Study Group 2: Interferon Alpha-2b |
|---|---|---|
| Arm/Group Description | Participants received vaccine treatment consisting of 3 series of multi-antigen ALVAC-based melanoma vaccine and GM-CSF injections, followed by four weeks of high-dose IFN-α2b. (Participants that did not show disease progression were allowed a second cycle of treatment) | Participants on Four weeks of high-dose IFN-α2b. (Participants that showed disease progression after Cycle 1 were permitted to cross over to Group 1 treatment) |
| Measure Participants | 9 | 12 |
| Screening: gp100 pool1 |
0
0%
|
0
0%
|
| Screening: gp100 pool2 |
0
0%
|
0
0%
|
| Screening: gp100 pool3 |
0
0%
|
0
0%
|
| Screening: gp100 pool4 |
0
0%
|
0
0%
|
| Screening: gp100 pool5 |
0
0%
|
0
0%
|
| Screening: gp100 pool6 |
0
0%
|
0
0%
|
| Screening: NYESO-1 pool 1 |
0
0%
|
0
0%
|
| Screening: NYESO-1 pool 2 |
0
0%
|
0
0%
|
| Screening: Mart1 pool |
0
0%
|
0
0%
|
| Screening: Native 15mer pool |
0
0%
|
0
0%
|
| Screening: 9mer pool |
0
0%
|
0
0%
|
| 7 Weeks post 1st Vaccination: gp100 pool1 |
0
0%
|
1
8.3%
|
| 7 Weeks post 1st Vaccination: gp100 pool2 |
0
0%
|
0
0%
|
| 7 Weeks post 1st Vaccination: gp100 pool3 |
0
0%
|
0
0%
|
| 7 Weeks post 1st Vaccination: gp100 pool4 |
0
0%
|
0
0%
|
| 7 Weeks post 1st Vaccination: gp100 pool5 |
1
9.1%
|
0
0%
|
| 7 Weeks post 1st Vaccination: gp100 pool6 |
0
0%
|
0
0%
|
| 7 Weeks post 1st Vaccination: NYESO-1 pool 1 |
0
0%
|
0
0%
|
| 7 Weeks post 1st Vaccination: NYESO-1 pool 2 |
0
0%
|
0
0%
|
| 7 Weeks post 1st Vaccination: Mart1 pool |
0
0%
|
0
0%
|
| 7 Weeks post 1st Vaccination: Native 15mer pool |
0
0%
|
0
0%
|
| 7 Weeks post 1st Vaccination: 9mer pool |
0
0%
|
0
0%
|
| Title | Best Overall Objective Response as Number of Participants Responding in the Intent-to-treat Population |
|---|---|
| Description | Objective response rate (ORR) is the sum of complete response (CR) and partial response (PR) Complete response = Disappearance of all target lesions. Partial response = At least a 30% decrease in the sum of longest diameter of target lesions, taking as reference the baseline sum longest diameter. |
| Time Frame | Day 0 to 32 weeks post 1st vaccination or treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| The best overall objective response as number of participants responding was assessed in the intent-to-treat (ITT) evaluable population. |
| Arm/Group Title | Study Group 1: ALVAC Melanoma Vaccine | Study Group 2: Interferon Alpha-2b |
|---|---|---|
| Arm/Group Description | Participants received vaccine treatment consisting of 3 series of multi-antigen ALVAC-based melanoma vaccine and GM-CSF injections, followed by four weeks of high-dose IFN-α2b. (Participants that did not show disease progression were allowed a second cycle of treatment) | Participants on Four weeks of high-dose IFN-α2b. (Participants that showed disease progression after Cycle 1 were permitted to cross over to Group 1 treatment) |
| Measure Participants | 11 | 12 |
| Participants with measurable disease at baseline |
11
|
11
|
| Complete Response (CR) |
0
|
0
|
| Partial Response (PR) |
2
|
1
|
| Stable Disease (SD) |
3
|
3
|
| Not Evaluable (NE) |
0
|
1
|
| Progression (PD) |
6
|
6
|
| Title | Best Overall Objective Response in the Intent-to-treat Population |
|---|---|
| Description | Objective response rate (ORR) is the sum of complete response (CR) and partial response (PR) Complete response = Disappearance of all target lesions. Partial response = At least a 30% decrease in the sum of longest diameter of target lesions, taking as reference the baseline sum longest diameter. |
| Time Frame | Day 0 to 32 weeks post 1st vaccination or treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| The best overall objective response were assessed in the intent-to-treat (ITT) evaluable population. |
| Arm/Group Title | Study Group 1: ALVAC Melanoma Vaccine | Study Group 2: Interferon Alpha-2b |
|---|---|---|
| Arm/Group Description | Participants received vaccine treatment consisting of 3 series of multi-antigen ALVAC-based melanoma vaccine and GM-CSF injections, followed by four weeks of high-dose IFN-α2b. (Participants that did not show disease progression were allowed a second cycle of treatment) | Participants on Four weeks of high-dose IFN-α2b. (Participants that showed disease progression after Cycle 1 were permitted to cross over to Group 1 treatment) |
| Measure Participants | 11 | 12 |
| Number [Percentage of participants] |
18.2
165.5%
|
9.1
75.8%
|
| Title | Summary of Disease Progression in Study Participants, Intent-to-treat Population |
|---|---|
| Description | Number of evaluable study participants who had died or experienced objective disease progression (no clinical objective response to treatment as evaluated by computed tomography [CT] scans or physical examination). |
| Time Frame | Day 0 up to 35 weeks post 1st vaccination or treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Progression-Free Survival Time were assessed in the intend-to-treat (ITT) evaluable population. |
| Arm/Group Title | Study Group 1: ALVAC Melanoma Vaccine | Study Group 2: Interferon Alpha-2b |
|---|---|---|
| Arm/Group Description | Participants received vaccine treatment consisting of 3 series of multi-antigen ALVAC-based melanoma vaccine and GM-CSF injections, followed by four weeks of high-dose IFN-α2b. (Participants that did not show disease progression were allowed a second cycle of treatment) | Participants on Four weeks of high-dose IFN-α2b. (Participants that showed disease progression after Cycle 1 were permitted to cross over to Group 1 treatment) |
| Measure Participants | 11 | 12 |
| Progressed or died due to any cause |
7
63.6%
|
6
50%
|
| Did not progress or die due to any cause |
4
36.4%
|
6
50%
|
| Title | Summary of Cellular Immune Response to the Vaccination or Treatment (Percent Regulatory T-Cells Responses) |
|---|---|
| Description | The immunogenicity of the treatment regimens was assessed by regulatory T-cell responses as assessed primarily by the multi-parametric intracellular cytokine staining (ICS) assay. |
| Time Frame | Day 0 to 32 weeks post 1st vaccination or treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Immunologic responses were assessed in the per-protocol evaluable population. |
| Arm/Group Title | Study Group 1: ALVAC Melanoma Vaccine | Study Group 2: Interferon Alpha-2b |
|---|---|---|
| Arm/Group Description | Participants received vaccine treatment consisting of 3 series of multi-antigen ALVAC-based melanoma vaccine and GM-CSF injections, followed by four weeks of high-dose IFN-α2b. (Participants that did not show disease progression were allowed a second cycle of treatment) | Participants on Four weeks of high-dose IFN-α2b. (Participants that showed disease progression after Cycle 1 were permitted to cross over to Group 1 treatment) |
| Measure Participants | 9 | 12 |
| Screening |
2.7
(1.02)
|
3.4
(1.24)
|
| Cycle 1 Week 1 |
3.3
(1.42)
|
2.3
(0.65)
|
| Cycle 1 Week 7 |
2.9
(0.83)
|
3.1
(1.13)
|
| Cycle 2 Week 23 |
3.3
(0.90)
|
3.8
(0.51)
|
| Cycle 2 Week 32 |
4.0
(0.48)
|
2.6
(0.07)
|
| Title | Progression-Free Survival Time by Response Evaluation Criteria in Solid Tumor (RECIST) Criteria in the Intent-to-treat Population |
|---|---|
| Description | Progression-Free Survival was assessed by the Response Evaluation Criteria in Solid Tumor criteria from the computed tomography (CT) scans, as per-protocol |
| Time Frame | Day 0 - up to 35 weeks post 1st vaccination or treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Progression-Free Survival Time were assessed in the intend-to-treat (ITT) evaluable population. |
| Arm/Group Title | Study Group 1: ALVAC Melanoma Vaccine | Study Group 2: Interferon Alpha-2b |
|---|---|---|
| Arm/Group Description | Participants received vaccine treatment consisting of 3 series of multi-antigen ALVAC-based melanoma vaccine and GM-CSF injections, followed by four weeks of high-dose IFN-α2b. (Participants that did not show disease progression were allowed a second cycle of treatment) | Participants on Four weeks of high-dose IFN-α2b. (Participants that showed disease progression after Cycle 1 were permitted to cross over to Group 1 treatment) |
| Measure Participants | 11 | 12 |
| Median (Inter-Quartile Range) [Weeks] |
15.9
|
8.9
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Study Group 1: ALVAC Melanoma Vaccine, Study Group 2: Interferon Alpha-2b |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9406 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Study Group 1: ALVAC Melanoma Vaccine, Study Group 2: Interferon Alpha-2b |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9179 |
| Comments | ||
| Method | Likelihood ratio test | |
| Comments | ||
| Title | Best Overall Objective Response as Mean Duration of Response (Weeks) in the Intent-to-treat Population |
|---|---|
| Description | Objective response rate (ORR) is the sum of complete response (CR) and partial response (PR) Complete response = Disappearance of all target lesions. Partial response = At least a 30% decrease in the sum of longest diameter of target lesions, taking as reference the baseline sum longest diameter. |
| Time Frame | Day 0 to 32 weeks post 1st vaccination or treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| The best overall objective response as mean duration of response were assessed in the intent-to-treat (ITT) evaluable population. |
| Arm/Group Title | Study Group 1: ALVAC Melanoma Vaccine | Study Group 2: Interferon Alpha-2b |
|---|---|---|
| Arm/Group Description | Participants received vaccine treatment consisting of 3 series of multi-antigen ALVAC-based melanoma vaccine and GM-CSF injections, followed by four weeks of high-dose IFN-α2b. (Participants that did not show disease progression were allowed a second cycle of treatment) | Participants on Four weeks of high-dose IFN-α2b. (Participants that showed disease progression after Cycle 1 were permitted to cross over to Group 1 treatment) |
| Measure Participants | 11 | 12 |
| Mean (Full Range) [Weeks] |
16.3
|
18.3
|
| Title | Number of Participants Reporting a Grade 3 or Grade 4 Adverse Events by Preferred Term |
|---|---|
| Description | Common Terminology Criteria for Adverse Events (CTCAE) definitions: Grade 3 is a severe adverse event; Grade 4 is a life-threatening or disabling adverse event. |
| Time Frame | Day 0 to 12 months post last vaccination |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety assessments were conducted in the As-treated safety population. |
| Arm/Group Title | Study Group 1: ALVAC Melanoma Vaccine | Study Group 2: Interferon Alpha-2b |
|---|---|---|
| Arm/Group Description | Participants received vaccine treatment consisting of 3 series of multi-antigen ALVAC-based melanoma vaccine and GM-CSF injections, followed by four weeks of high-dose IFN-α2b. (Participants that did not show disease progression were allowed a second cycle of treatment) | Participants on Four weeks of high-dose IFN-α2b. (Participants that showed disease progression after Cycle 1 were permitted to cross over to Group 1 treatment) |
| Measure Participants | 11 | 12 |
| Anemia |
0
0%
|
1
8.3%
|
| Leukocytosis |
1
9.1%
|
0
0%
|
| Abdominal Pain Upper |
1
9.1%
|
0
0%
|
| Axillary Pain |
1
9.1%
|
0
0%
|
| Chest Discomfort |
1
9.1%
|
0
0%
|
| Chest Pain |
1
9.1%
|
0
0%
|
| Inflammation |
1
9.1%
|
0
0%
|
| Pyrexia |
0
0%
|
1
8.3%
|
| Sepsis |
1
9.1%
|
0
0%
|
| Septic Shock |
0
0%
|
1
8.3%
|
| Staphylococcal Bacteremia |
0
0%
|
1
8.3%
|
| Alanine Aminotransferase (ALT) Increased |
0
0%
|
3
25%
|
| Aspartate Aminotransferase (AST) Increased |
0
0%
|
1
8.3%
|
| Gamma-Glutamyl Transferase (GGT) Increased |
1
9.1%
|
1
8.3%
|
| Neutrophil Count Decreased |
1
9.1%
|
0
0%
|
| White Blood Cell Count Decreased |
1
9.1%
|
0
0%
|
| Hypernatremia |
1
9.1%
|
0
0%
|
| Hypoalbuminemia |
0
0%
|
1
8.3%
|
| Hypocalcemia |
0
0%
|
1
8.3%
|
| Hyponatremia |
0
0%
|
1
8.3%
|
| Joint Range of Motion Decreased |
1
9.1%
|
0
0%
|
| Metastatic Malignant Melanoma |
0
0%
|
1
8.3%
|
| Brain Edema |
1
9.1%
|
0
0%
|
| Cerebral Hemorrhage |
1
9.1%
|
0
0%
|
| Encephalopathy |
1
9.1%
|
0
0%
|
| Headache |
1
9.1%
|
0
0%
|
| Hemiplegia |
1
9.1%
|
0
0%
|
| Paraesthesia |
0
0%
|
1
8.3%
|
| Peripheral Sensory Neuropathy |
0
0%
|
1
8.3%
|
| Syncope Vasovagal |
0
0%
|
1
8.3%
|
| Polyuria |
1
9.1%
|
0
0%
|
| Hypotension |
1
9.1%
|
0
0%
|
Adverse Events
| Time Frame | Adverse events data were collected from the day of vaccination for 12 months post-vaccination | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Due to the very limited data on the cross over participants in Group 2, Cycle 2 (n=4), cross over data were only reflected in the serious adverse event (SAE) data. Three of the 4 participants reported Gastrointestinal perforation, chest pain, disease progression, and pneumonia SAEs during the 12 months follow-up period. | |||
| Arm/Group Title | Study Group 1: ALVAC Melanoma Vaccine | Study Group 2: Interferon Alpha-2b | ||
| Arm/Group Description | Participants received vaccine treatment consisting of 3 series of multi-antigen ALVAC-based melanoma vaccine and GM-CSF injections, followed by four weeks of high-dose IFN-α2b. (Participants that did not show disease progression were allowed a second cycle of treatment) | Participants on Four weeks of high-dose IFN-α2b. (Participants that showed disease progression after Cycle 1 were permitted to cross over to Group 1 treatment) | ||
All Cause Mortality |
||||
| Study Group 1: ALVAC Melanoma Vaccine | Study Group 2: Interferon Alpha-2b | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Study Group 1: ALVAC Melanoma Vaccine | Study Group 2: Interferon Alpha-2b | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/11 (45.5%) | 5/12 (41.7%) | ||
| Gastrointestinal disorders | ||||
| Gastrointestinal Perforation | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| General disorders | ||||
| Disease Progression | 2/11 (18.2%) | 2 | 2/12 (16.7%) | 2 |
| Chest Pain | 1/11 (9.1%) | 1 | 1/12 (8.3%) | 1 |
| Infections and infestations | ||||
| Sepsis | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Septic Shock | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Pneumonia | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Metastatic Malignant Melanoma | 2/11 (18.2%) | 2 | 0/12 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Study Group 1: ALVAC Melanoma Vaccine | Study Group 2: Interferon Alpha-2b | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/11 (45.5%) | 7/12 (58.3%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Leukocytosis | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal Pain Upper | 1/11 (9.1%) | 2 | 0/12 (0%) | 0 |
| General disorders | ||||
| Axillary Pain | 1/11 (9.1%) | 2 | 0/12 (0%) | 0 |
| Chest Discomfort | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Inflammation | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Pyrexia | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Infections and infestations | ||||
| Staphylococcal Bacteremia | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Investigations | ||||
| ALT Increased | 0/11 (0%) | 0 | 3/12 (25%) | 3 |
| AST Increased | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| GGT Increased | 1/11 (9.1%) | 1 | 1/12 (8.3%) | 1 |
| Neutrophil Count Decreased | 1/11 (9.1%) | 3 | 0/12 (0%) | 0 |
| White Blood Cell Count Decreased | 1/11 (9.1%) | 3 | 0/12 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Hypernatremia | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Hypoalbuminemia | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hypocalcemia | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hyponatremia | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Joint Range of Motion Decreased | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Nervous system disorders | ||||
| Brain Edema | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Cerebral Hemorrhage | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Encephalopathy | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Headache | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Hemiplegia | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Paraesthesia | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Peripheral Sensory Neuropathy | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Syncope Vasovagal | 0/11 (0%) | 0 | 1/12 (8.3%) | 1 |
| Renal and urinary disorders | ||||
| Polyuria | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
| Vascular disorders | ||||
| Hypotension | 1/11 (9.1%) | 1 | 0/12 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Sanofi Pasteur Inc. |
| Phone | |
| RegistryContactUs@sanofipasteur.com |
- MEL11