Combination Immunotherapy and Autologous Stem Cell Transplantation for Myeloma
Condition: Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      One purpose of this study is to find out if a new combination of immune system treatments
      (MAGE-A3 vaccine plus activated T-cells) will allow the body to build up protection
      ("immunity") against the myeloma cells. A second purpose is to find out how well this
      combination of immune system treatments is able to control the myeloma.
    

Detailed description: 
      Autologous stem cell transplant (ASCT) can lead to a complete or partial disappearance of the
      myeloma in about 2 out of 3 patients. However, an ASCT only sometimes leads to a cure of the
      myeloma. In about half the patients the myeloma comes back after about 1-2 years. In about
      90% of patients it comes back by about 10 years after transplant.

      One possible way to improve upon the results of ASCT for myeloma is to help the body's
      defense or immune system recover faster after transplant. Another way is to teach the body's
      immune system to fight against the myeloma cells.

      In two earlier research studies which included more than 100 patients, certain types of
      immune cells called "T cells" or "T lymphocytes" were taken out of a patient's body using a
      procedure called "apheresis". These cells were then grown up in the lab. After the
      transplant, these T cells were put back into the patients. The replaced T cells helped the
      patients'immune systems to recover faster after the transplant. In addition, when the T cells
      were given back to patients they also received a vaccination. The vaccination or injection
      was for a certain type of pneumonia germ called "pneumococcus". We found that most patients
      built up protection against this pneumonia-causing germ. In another study, we used a possible
      myeloma cancer vaccine. However, we found that less than half the patients responded to this
      vaccine.

      In this new study, we want to test a different type of myeloma cancer vaccine. This different
      cancer vaccine is based on a protein called MAGE-A3. The MAGE-A3 protein is found in about
      50% of cases of myeloma. This vaccine consists of small pieces of protein (called "peptides")
      which come from the MAGE-A3 protein. In order to help the immune system respond better we
      will add two new steps. First we will add an immune system stimulant called "Hiltonol®" to
      each vaccination. Hiltonol® is a chemical substance that turns on several parts of the immune
      system. It may make the immune system better able to respond to the vaccine. It has been
      tested in several hundred patients and has been used with about a dozen different types of
      cancer and germ vaccines. Second, starting about 100 days after the transplant procedure,
      patients will get a medicine called Lenalidomide. Lenalidomide is already approved by the
      Food and Drug Administration (FDA) for treatment of myeloma. In this study, we want to know
      whether Lenalidomide could help to improve the body's ability to respond to the vaccinations
      and help to treat the myeloma itself.
    

Intervention name(s): Prevnar- Pneumococcal Conjugate Vaccine (PCV); Activated/costimulated autologous T-cell; Revlamid® (Lenalidomide); MAGE-A3/GM-GSF, Hiltonol® (Poly-ICLC)
Intervention type(s): Biological; Other; Drug; Biological
Intervention description(s): After study enrollment, patients will receive Prevnar- Pneumococcal Conjugate Vaccine (PCV). At Day #14, Day #42, and Day #90, Day #120 and Day #150, patients will receive a booster immunization with Prevnar- Pneumococcal Conjugate Vaccine (PCV).; For all patients, the cells will be expanded ex vivo for up to 12 days and then prepared for infusion ~day 2 post-transplant. The target number of costimulated T-cells for infusion will be ~ 5 x 10e10 T-cells total in 100-500 mL total volume.; At about day 100 post-transplant, after completion of post-transplant immunological assessments and myeloma restaging studies, patients will be eligible to receive low-dose Revlamid® (Lenalidomide) 10 mg/day for maintenance therapy (10 mg/day) until progression of myeloma or development of intolerance.; After study enrollment, patients will receive both MAGE-A3/GM-CSF [+ coinjection of 2mg of Hiltonol®(Poly-ICLC)]. At Day #14, Day #42, Day #90, Day #120 and Day #150 patients will receive an additional immunization with MAGE-A3/GM-GSF, Hiltonol® (Poly-ICLC).
Intervention MeSH terms: Lenalidomide; Heptavalent Pneumococcal Conjugate Vaccine; Poly ICLC
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Advanced Disease; MAGE-A3 Immunizations with Hiltonol; Vaccine-Primed Autologous T-Cells; Lenalidomide Maintenance