Phase IIB TL + YCWP + DC in Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Study type: Interventional
Phase: Phase 2

Summary: 
      The majority of melanoma vaccines tested to date have been antigen-specific vaccines
      targeting melanoma-specific or associated antigens and utilizing a variety of delivery
      systems and immune-adjuvants. As opposed to testing an "off the shelf" vaccine that might be
      able to treat a subset of patients, our approach has been personalized to the patient and
      applicable to all patients. Our vaccine approach consists of harnessing the most potent
      antigen presenting cell in the body - the dendritic cell (DC) - together with the full
      repertoire of tumor antigens from an individual's cancer. We have conducted phase I and II
      studies using an autologous DC-tumor cell fusion technique that has now been simplified into
      a DC-tumor cell lysate vaccine. The autologous tumor lysate (TL) is loaded into yeast cell
      wall particles (YCWP) that are naturally and efficiently taken up into the patient's DC.
      These autologous tumor lysate, particle-loaded, DC (TLPLDC) are injected intradermally (ID)
      monthly x 3 followed by boosters at 6, 12, and 18 months.
    

Detailed description: 
      Stage III and Stage IV (resected) melanoma patients will be identified prior to definitive
      surgery and screened for inclusion/exclusion criteria. Eligible patients will be counseled
      and consented for tissue procurement. Enrolled patients will have their disease surgically
      resected and a portion 1mg minimum of their melanoma sterilely frozen in provided freezing
      vials and storage tubes. This tissue will be shipped in liquid nitrogen shippers through
      FedEx to our central facility in Greenville SC and stored frozen until vaccine preparation.
      If patients cannot be rendered disease-free, they will be considered screen failures for this
      study. If melanoma is being resected from multiple locations primary and nodes two different
      metastatic sites then samples of each would be preferred but not mandatory.

      As indicated by SoC per the National Comprehensive Cancer Network (NCCN) guidelines and
      determined by the treating team, if a patient is to receive systemic therapy (chemotherapy or
      IFN-aguidelines) and determined by the treating team, if a patient is to receive systemic
      therapy (chemotherapy or IFN-central facility in Greenville, SC) and stored frozen until
      vaccine preparation. If patients cannot be rendered disease-free, they will receive a single
      injection of Neupogen (G-CSF) 300 mod (or its equivalent) SQ 24-48 hrs. prior to having 70 mL
      of blood collected and sent to our central facility for DC isolation and preparation.
      Patients who cannot tolerate Neupogen, or its equivalent or refuse it, will have 120 mL of
      blood drawn and sent. Additional blood may be drawn if additional vaccine doses need to be
      made or re-made for any reason. Vaccines will be prepared by producing TL through freeze/thaw
      cycling and then loaded into pre-prepared YCWP. The TL-loaded YCWP will be introduced to the
      DC for phagocytosis thus creating the TLPLDC vaccine which will be frozen in single dose
      vials. Each vial will contain 1-1.5 x 106 TLPLDC and will be labeled with the patient's
      unique study number.

      Based on their randomization, autologous TLPLDC (active vaccine) or unloaded YCWP +
      autologous DC (control) will be sent back to the site in a blinded fashion. Regardless of
      assigned group, the site will receive 6 single dose vials to be injected intradermal monthly
      x 3 followed by boosters at 6, 12, and 18 months in the same lymph node draining area
      (preferably the anterior thigh). Patients must begin vaccinations between 3 weeks and 3
      months from completion of (SoC). Frozen tumor will be maintained for active vaccines for all
      patients to include the control patients. The latter will be offered their active vaccine at
      time of recurrence in a crossover fashion. Additionally, control patients who do not recur
      will be offered active vaccine at the completion of the trial.

      Safety data will be collected on local and systemic toxicities and graded and reported per
      the Common Terminology Criteria for Adverse Events (CTCAE) v4.03.

      Disease-free status will be monitored per SoC as outlined by NCCN. Suspected recurrences will
      be documented with biopsy and pathologic confirmation. Time to recurrence will be based on
      date of randomization to time of confirmed recurrence.

      Recurrent patients will be offered participation in the open label portion of the study. New
      active vaccine will be made for all patients, and they will be inoculated at 0, 1, 2, 3, 6,
      and 9 mos. Patients will be treated per SoC for their recurrence. Safety and tumor response
      will be assessed per RECIST and irRC on their SoC follow-up scans.

      Blood (50 mL) will be collected from all patients prior to each inoculation and at 24 months
      from enrollment for a total of 7 time points or a total of 350 mL of blood over 2 years. The
      collected blood will be sent to our central facility for immunologic testing of the T-cell
      response.
    

Intervention name(s): TLPLDC; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Autologous tumor lysate, particle-loaded dendritic cell vaccine
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment