MelanomaPhase 3NCT00477906
M-Vax + Low Dose Interleukin-2 Versus Placebo Vaccine in Metastatic Melanoma in Patients With Stage IV Melanoma
A Phase 3 study testing M-Vax- autologous, hapten-modified melanoma vaccine in people with Melanoma, run by AVAX Technologies.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Melanoma
- What is being tested?
- M-Vax- autologous, hapten-modified melanoma vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 387 participants
- Where
- No sites listed yet
- Study dates
- Jul 2016to Jan 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- Expected survival of at least 6 months
- Karnofsky performance status at least 80
- Signed informed consent
Who cannot join
- 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
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- 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)
Trial locations and contacts
No sites are listed yet.
About this study
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
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.
Read more
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.
Read the 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.
- Conditions
- Melanoma
- Being tested
- M-Vax- autologous, hapten-modified melanoma vaccine
- Keywords
- melanoma, vaccine, metastatic, autologous
- Medical subject headings
- Melanoma, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
M-Vax- autologous, hapten-modified melanoma vaccineBiological
Autologous, DNP-modified melanoma cells in suspension Dose: 12+-8 million cells Route: intradermal Frequency: weekly X7 + 6 month booster
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | MVax + BCG + cyclophosphamide + IL2
2:1 randomization - MVax:Control Receives: Biological: M-Vax- autologous, hapten-modified melanoma vaccine |
| 2 | Placebo comparator | Placebo Vaccine + BCG + cyclophosphamide + IL2 Receives: Biological: M-Vax- autologous, hapten-modified melanoma vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best overall anti-tumor response.
Measured: 1 year
Survival - % patients surviving at two years
Measured: 2 years
Secondary outcomes (1)
Safety
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2007 (estimated)
- Study startJul 2016
- Primary completionJan 2019 (estimated)
- Study completionJan 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 387 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AVAX Technologies
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Henry E Schea, Study director, AVAX Technologies
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00477906
- Sponsor's protocol ID
- A/100/0402
- Status last verified
- Dec 2015
- First submitted
- 22 May 2007
- Last updated
- 3 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 14691123Berd 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.
PubMed 11745440
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00477906
- Acronym / sponsor ID
- A/100/0402
- Conditions
- Melanoma
- Keywords
- melanoma, vaccine, metastatic, autologous
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 387 participants (estimated)
- Lead sponsor
- AVAX TechnologiesIndustry (pharma, biotech, devices)
- Study start
- Jul 2016
- Primary completion
- Jan 2019 (estimated)
- Study completion
- Jan 2021 (estimated)
- First posted
- 24 May 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: M-Vax- autologous, hapten-modified melanoma vaccineMVax + BCG + cyclophosphamide + IL2 2:1 randomization - MVax:Control |
| 2 | Placebo comparator | Biological: M-Vax- autologous, hapten-modified melanoma vaccinePlacebo Vaccine + BCG + cyclophosphamide + IL2 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Stage IV metastatic melanoma of cutaneous or mucosal origin or without known primary site
Key exclusion criteria (27 listed)
- Failure to prepare a vaccine that meets all quality control release criteria
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| M-Vax- autologous, hapten-modified melanoma vaccineAutologous, DNP-modified melanoma cells in suspension Dose: 12+-8 million cells Route: intradermal Frequency: weekly X7 + 6 month booster | Biological | 1, 2 |
Primary outcome
Best overall anti-tumor response.
Time frame: 1 year
Survival - % patients surviving at two years
Time frame: 2 years
1 secondary outcome
Safety
Time frame: 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2015.
- Background: PubMed 14691123Berd 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 publication: PubMed 11745440Berd 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Henry E Schea study director
AVAX Technologies
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing M-Vax- autologous, hapten-modified melanoma vaccine in people with Melanoma, run by AVAX Technologies.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Henry E Schea (215 241-9760 ext. 1302, henry@avax-tech.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Best overall anti-tumor response. (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00477906, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2015.