Know Cancer

forgot password

Comparison of M-Vax Plus Low Dose Interleukin-2 Versus Placebo Vaccine Plus Low Dose Interleukin-2 in Patients With Stage IV Melanoma

Phase 3
Open (Enrolling)

Thank you

Trial Information

Comparison of M-Vax Plus Low Dose Interleukin-2 Versus Placebo Vaccine Plus Low Dose Interleukin-2 in Patients With Stage IV Melanoma

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.

Inclusion Criteria:

- Stage IV metastatic melanoma of cutaneous or mucosal origin or without known primary

- 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

- 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)

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Best overall anti-tumor response.

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Henry E Schea

Investigator Role:

Study Director

Investigator Affiliation:

AVAX Technologies


United States: Food and Drug Administration

Study ID:




Start Date:

July 2007

Completion Date:

Related Keywords:

  • Melanoma
  • melanoma
  • vaccine
  • metastatic
  • autologous
  • Melanoma