M-Vax + Low Dose Interleukin-2 Versus Placebo Vaccine in Metastatic Melanoma in Patients With Stage IV Melanoma
Primary Purpose
Melanoma
Status
Unknown status
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
M-Vax- autologous, hapten-modified melanoma vaccine
Sponsored by
About this trial
This is an interventional treatment trial for Melanoma focused on measuring melanoma, vaccine, metastatic, autologous
Eligibility Criteria
Inclusion Criteria:
Stage IV metastatic melanoma of cutaneous or mucosal origin or without known primary site
- At least one metastatic mass that is surgically resectable, excluding metastases in brain, bowel, or bone
- Successful preparation of a vaccine that meets quality control release criteria
- Following surgery for vaccine preparation, subjects must have at least one measurable metastasis defined by modified RECIST criteria. Non-measurable metastases may also be present. Residual metastases (measurable or non-measurable) must be limited to skin (dermal or subcutaneous), lymph node, or lung, or a combination of these.
- No prior systemic treatment or one prior systemic treatment for metastatic melanoma, not counting post-surgical adjuvant treatment with alpha interferon
- Minimum of one month and maximum of 4 months since the surgery
- Expected survival of at least 6 months
- Karnofsky performance status at least 80
- Signed informed consent
Exclusion Criteria:
Failure to prepare a vaccine that meets all quality control release criteria
- Uveal melanoma
- Post-surgical residual metastases in sites other than specified in 6.1
- Brain metastases, current or past (unless successfully treated at least one year prior to enrollment)
- Hepatic transaminase > 2.5 x ULN
- Total bilirubin > 2.0 mg/Dl
- Creatinine > 2.0 mg/Dl
- Hemoglobin < 10.0 g/Dl
- WBC < 3,000 /mm3
- Platelet count < 100,000/mm3
- Limited field radiotherapy, i.e., limited to recent surgical site, less than 4 weeks prior to first dose of vaccine
- Major field radiotherapy less than 6 months prior to first dose of vaccine
- Any systemic treatment for metastatic melanoma, including chemotherapy, cytokines, or investigational drugs less than 2 months prior to first dose of vaccine
- Previous administration of M-Vax
- Prior splenectomy
- Administration of systemic steroids less than 4 weeks prior to first dose of vaccine. Topical steroids are allowed during the study, provided these are not applied to vaccine injection sites. Inhaled aerosol steroids also are allowed during the study.
- Administration of immunosuppressive drugs less than 4 weeks prior to first dose of vaccine
- Administration of antitubercular drugs (e.g., isoniazid, rifampin, streptomycin) less than 4 weeks prior to first dose of vaccine
- HIV 1/2 positive by ELISA, confirmed by Western blot
- Hepatitis B surface antigen or hepatitis C antibody positive
- Other malignancy within 5 years except: curatively treated non-invasive melanoma, non-melanomatous skin cancer, carcinoma in situ of the uterine cervix, or early stage (stage A or B1) prostate cancer
- Autoimmune diseases that would interfere with an immunologic response (e.g., systemic lupus erythematosus, multiple sclerosis or ankylosing spondylitis)
- Concurrent medical condition that would preclude compliance or immunologic response to study treatment
- Concurrent serious infection, including active tuberculosis, or other serious medical condition
- Pregnancy or lactation (serum human chorionic gonadotropin [HCG] test must be negative in fertile women at screening visit)
- Known gentamicin allergy
- Anergic, defined by the inability to make a DTH to at least one of the following: candida, mumps, tetanus or trichophyton (based upon availability)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
1
2
Arm Description
MVax + BCG + cyclophosphamide + IL2 2:1 randomization - MVax:Control
Placebo Vaccine + BCG + cyclophosphamide + IL2
Outcomes
Primary Outcome Measures
Best overall anti-tumor response.
Survival - % patients surviving at two years
Secondary Outcome Measures
Safety
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00477906
Brief Title
M-Vax + Low Dose Interleukin-2 Versus Placebo Vaccine in Metastatic Melanoma in Patients With Stage IV Melanoma
Official Title
Comparison of M-Vax Plus Low Dose Interleukin-2 Versus Placebo Vaccine Plus Low Dose Interleukin-2 in Patients With Stage IV Melanoma
Study Type
Interventional
2. Study Status
Record Verification Date
December 2015
Overall Recruitment Status
Unknown status
Study Start Date
July 2016 (undefined)
Primary Completion Date
January 2019 (Anticipated)
Study Completion Date
January 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AVAX Technologies
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Previous studies suggests that M-Vax, a melanoma vaccine prepared from patients own cancer cells, can stimulated patients' immune system to react against their cancer. AVAX has identified a dose and schedule of administration of M-Vax that work optimally. In this study, AVAX will determine whether M-Vax is effective in shrinkage of melanomas that have spread (stage IV). To increase it effectiveness, M-Vax administration will be followed by administration of low doses of interleukin-2 (IL2), a marketed drug that is known to stimulate immunity and cause some shrinkage of melanomas. Two-thirds of patients will receive M-Vax + IL2, and one-third will receive a placebo vaccine + IL2. The study is blinded so that neither the patients nor their physicians know which material they are receiving.
To be eligible for this study, patients must have at least one melanoma tumor that can be surgically removed and made into a vaccine. In addition, they must have melanoma that has spread to to the lungs or to soft tissue sites (under the skin, on the surface of the skin, lymph nodes). Eligible patients may have previously received one treatment (for example, chemotherapy) for their melanoma.
Side effects of M-Vax are expected to be mild; the most common is the development of sore pimples at the site of vaccine injections. The low dose IL2 may cause some fatigue and other mild symptoms.
It is expected that 387 patients will be treated in this study.
Detailed Description
M-Vax is a therapeutic melanoma vaccine consisting of autologous melanoma cells that have been irradiated and then modified with the hapten, dinitrophenyl (DNP). There is a large amount of published evidence that hapten modification makes visible to the immune system antigens, including tumor antigens, that otherwise do not elicit an immune response.
This is a Phase III, randomized, placebo-controlled, double-blind, multi-centered trial of M-Vax in patients with stage IV melanoma with measurable metastases in lung and/or soft tissues. To be eligible for screening, patients will have undergone surgery for therapeutic intervention, which yields an adequate amount of melanoma tumor cells for preparation of vaccines, which pass vaccine release testing. Eligible patients who meet all inclusion/exclusion criteria will be enrolled in the study.
Patients will be assigned in a double-blind fashion to M-Vax or Placebo Vaccine at a 2:1 ratio (M-Vax:Placebo Vaccine). The dose of M-Vax will be 4.0-20.0x10(6) DNP-modified autologous melanoma tumor cells. The Placebo Vaccine will consist of diluent only. An initial dose of M Vax or Placebo Vaccine will be administered without BCG followed by low dose cyclophosphamide (300 mg/m2 iv). Then M Vax or Placebo Vaccine mixed with Bacillus of Calmette and Guérin (BCG) will be administered weekly for 6 weeks. Four courses of interleukin-2 (IL2) will be administered to all patients starting about 2 weeks after the last vaccine; each course will consist of 3 million units/m2 subcutaneously daily for 5 days followed by a 16-day rest period.
The primary endpoints of the study are: 1)Best overall anti-tumor response, and 2)Survival, measured by % surviving at two years. Patients will be evaluated for anti-tumor response by modified RECIST criteria between weeks 24 and 25 (i.e., 5-6 weeks after completion of IL2). At the 6-month point patients who remain on study will receive an additional single booster dose of M-Vax or Placebo Vaccine mixed with BCG. This will be followed by four more courses of IL2. Two additional evaluations for anti-tumor response will take place at the 38-39 week (month 9) and one-year points. Then patients will be regularly evaluated for tumor status and adverse events until evidence of tumor progression that requires new therapy. Patients who remain on-study will be followed until death but for a maximum of 5 years.
The intended sample size is 387, and there will be about 25 sites participating in the United States, Europe, and Israel. An interim analysis will be performed after half the patients have been accrued.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
melanoma, vaccine, metastatic, autologous
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
387 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
MVax + BCG + cyclophosphamide + IL2
2:1 randomization - MVax:Control
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Placebo Vaccine + BCG + cyclophosphamide + IL2
Intervention Type
Biological
Intervention Name(s)
M-Vax- autologous, hapten-modified melanoma vaccine
Intervention Description
Autologous, DNP-modified melanoma cells in suspension Dose: 12+-8 million cells Route: intradermal Frequency: weekly X7 + 6 month booster
Primary Outcome Measure Information:
Title
Best overall anti-tumor response.
Time Frame
1 year
Title
Survival - % patients surviving at two years
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Safety
Time Frame
5 years
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Stage IV metastatic melanoma of cutaneous or mucosal origin or without known primary site
At least one metastatic mass that is surgically resectable, excluding metastases in brain, bowel, or bone
Successful preparation of a vaccine that meets quality control release criteria
Following surgery for vaccine preparation, subjects must have at least one measurable metastasis defined by modified RECIST criteria. Non-measurable metastases may also be present. Residual metastases (measurable or non-measurable) must be limited to skin (dermal or subcutaneous), lymph node, or lung, or a combination of these.
No prior systemic treatment or one prior systemic treatment for metastatic melanoma, not counting post-surgical adjuvant treatment with alpha interferon
Minimum of one month and maximum of 4 months since the surgery
Expected survival of at least 6 months
Karnofsky performance status at least 80
Signed informed consent
Exclusion Criteria:
Failure to prepare a vaccine that meets all quality control release criteria
Uveal melanoma
Post-surgical residual metastases in sites other than specified in 6.1
Brain metastases, current or past (unless successfully treated at least one year prior to enrollment)
Hepatic transaminase > 2.5 x ULN
Total bilirubin > 2.0 mg/Dl
Creatinine > 2.0 mg/Dl
Hemoglobin < 10.0 g/Dl
WBC < 3,000 /mm3
Platelet count < 100,000/mm3
Limited field radiotherapy, i.e., limited to recent surgical site, less than 4 weeks prior to first dose of vaccine
Major field radiotherapy less than 6 months prior to first dose of vaccine
Any systemic treatment for metastatic melanoma, including chemotherapy, cytokines, or investigational drugs less than 2 months prior to first dose of vaccine
Previous administration of M-Vax
Prior splenectomy
Administration of systemic steroids less than 4 weeks prior to first dose of vaccine. Topical steroids are allowed during the study, provided these are not applied to vaccine injection sites. Inhaled aerosol steroids also are allowed during the study.
Administration of immunosuppressive drugs less than 4 weeks prior to first dose of vaccine
Administration of antitubercular drugs (e.g., isoniazid, rifampin, streptomycin) less than 4 weeks prior to first dose of vaccine
HIV 1/2 positive by ELISA, confirmed by Western blot
Hepatitis B surface antigen or hepatitis C antibody positive
Other malignancy within 5 years except: curatively treated non-invasive melanoma, non-melanomatous skin cancer, carcinoma in situ of the uterine cervix, or early stage (stage A or B1) prostate cancer
Autoimmune diseases that would interfere with an immunologic response (e.g., systemic lupus erythematosus, multiple sclerosis or ankylosing spondylitis)
Concurrent medical condition that would preclude compliance or immunologic response to study treatment
Concurrent serious infection, including active tuberculosis, or other serious medical condition
Pregnancy or lactation (serum human chorionic gonadotropin [HCG] test must be negative in fertile women at screening visit)
Known gentamicin allergy
Anergic, defined by the inability to make a DTH to at least one of the following: candida, mumps, tetanus or trichophyton (based upon availability)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Henry E Schea
Phone
215 241-9760
Ext
1302
Email
henry@avax-tech.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Henry E Schea
Organizational Affiliation
AVAX Technologies
Official's Role
Study Director
12. IPD Sharing Statement
Citations:
PubMed Identifier
14691123
Citation
Berd D, Sato T, Maguire HC Jr, Kairys J, Mastrangelo MJ. Immunopharmacologic analysis of an autologous, hapten-modified human melanoma vaccine. J Clin Oncol. 2004 Feb 1;22(3):403-15. doi: 10.1200/JCO.2004.06.043. Epub 2003 Dec 22.
Results Reference
background
PubMed Identifier
11745440
Citation
Berd D, Sato T, Cohn H, Maguire HC Jr, Mastrangelo MJ. Treatment of metastatic melanoma with autologous, hapten-modified melanoma vaccine: regression of pulmonary metastases. Int J Cancer. 2001 Nov;94(4):531-9. doi: 10.1002/ijc.1506.abs.
Results Reference
result
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M-Vax + Low Dose Interleukin-2 Versus Placebo Vaccine in Metastatic Melanoma in Patients With Stage IV Melanoma
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