Study of MAGE-A3 and NY-ESO-1 Immunotherapy in Combo With DTPACE Chemo and Auto Transplantation in Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The hope is that the peptide vaccines will stimulate the immune system to attack and kill the
      myeloma cells. The purpose is to generate anti-myeloma T-cells which will kill myeloma cells
      and nothing else.
    

Detailed description: 
      This is an experimental treatment that will consist of receiving peptide vaccinations as a
      shot just under the skin (subcutaneous). We have chosen to vaccinate with peptides derived
      from cancer proteins found in myeloma and other cancers. The purpose is to generate
      anti-myeloma T-cells which will kill myeloma cells and nothing else.

      The peptides are fragments from two tumor proteins called MAGE-A3 and NY-ESO-1. In order to
      be eligible for the study your myeloma cells must express either MAGE-A3 or NY-ESO-1, and
      your myeloma must be severe enough to require chemotherapy and stem cell transplantation. You
      must also have the appropriate HLA tissue type.

      Patients who have MAGE-A3 positive myeloma and are HLA-A*0101 or -B*35 positive will receive
      the MAGE-A3 peptide vaccine.

      Patients who have NY-ESO-1 positive myeloma and are HLA-A*0201 will receive the NY-ESO-1
      peptide vaccine.

      Three injections with 300µg per injection (in 1.5mls) of peptide will be given subcutaneously
      together with the adjuvant GM-CSF at 500µg (same site in 0.5 mls) at two-week intervals.

      Your myeloma cells, obtained from a routine bone marrow aspirate, will be tested in the
      laboratory for the presence of MAGE-A3 and/or NY-ESO-1 proteins. HLA tissue type will be
      determined by standard methods in our Clinical Laboratory. This allows allocation of the
      correct vaccine to each individual patient.

      Prior to starting a 6-day course of chemotherapy called DTPACE, white blood cells will be
      collected by a procedure called leukapheresis (leukapheresis no.1). Your white blood cells
      will be frozen for the duration of the chemotherapy in order to protect these white blood
      cells from the harmful effects of chemotherapy. After the chemotherapy is given, stem cells
      will be collected by leukapheresis (PBSC collection) and stored until the time of
      transplantation. After a short period of rest, the white blood cells from leukapheresis no.1
      will be thawed and re-infused. This will ensure that you will have white blood cells that are
      in the best possible condition to respond to the peptide vaccines. A set of three
      vaccinations with the peptides at two-week intervals will follow. The hope is that the
      vaccinations will have generated precious anti-myeloma white blood cells.

      You will again undergo leukapheresis (leukapheresis no.2) to collect the anti-myeloma white
      blood cells, which will be frozen in order to protect these precious cells from the
      chemotherapy drugs that will be infused just before the single or double auto-transplant.

      A single dose of Melphalan will precede each transplant. The stem cells that were collected
      after DTPACE will be given for the transplants. For those receiving two transplants, a
      regimen of thalidomide with dexamethasone will be given for approximately 10 weeks between
      the two transplants. You will stop your thalidomide 28 days before the second transplant.

      After completion of the transplants, the anti-myeloma white blood cells collected with
      leukapheresis no. 2 will be thawed and re-infused. These anti-myeloma cells will be boosted
      by three further peptide vaccinations at two-week intervals.

      Finally, after you have completed these three vaccinations you will undergo another
      leukapheresis (no. 3). The anti-myeloma white blood cells collected with leukapheresis no. 3
      will be frozen and stored for possible future use.

      Six final vaccines will be given at monthly intervals to further amplify the anti-myeloma
      white blood cells.
    

Intervention name(s): MAGE-A3; MAGE-A3 AND NY-ESO-1 IMMUNOTHERAPY
Intervention type(s): Biological; Biological
Intervention description(s): vaccinations at 2- week intervals (days 22,36,50) with the MAGE-A3 or NY-ESO-1 peptide and GM-CSF adjuvant. The peptides will be given s.c. in a dose of 300μg; GM-CSF (250μg) will be administered to promote attraction, maturation and longevity of DCs. #2 will be thawed and re-infused after transplant on day 81 and any anti-myeloma T-cells in this leukapheresis product will be boosted immediately by re-vaccinating the patient 3 times at 14 day intervals (vaccination #4-6: days 82, 96, and 110). Vaccines #4-6 will be identical to vaccines 1-3. Thereafter, 6 monthly vaccines will be given to further boost the anti-MM-T-cells.; Three injections with 300µg per injection (in 1.5mls) of peptide will be given subcutaneously together with the adjuvant GM-CSF at 500µg (same site in 0.5 mls) at two-week intervals
Intervention MeSH terms: Immunomodulating Agents
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Myeloma; Mage-A3; Transplant; Peptide; DTPACE; vaccines; Immunotherapy; NY-ESO-1