Combination Immunotherapy and Autologous Stem Cell Transplantation for Myeloma
Condition: Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Prevnar- Pneumococcal Conjugate Vaccine (PCV); Activated/costimulated autologous T-cell; Revlamid® (Lenalidomide); MAGE-A3/GM-GSF, Hiltonol® (Poly-ICLC)
Intervention description: 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
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Advanced Disease; MAGE-A3 Immunizations with Hiltonol; Vaccine-Primed Autologous T-Cells; Lenalidomide Maintenance

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent

          -  Patients must be registered with the Sponsor's Monitor

          -  Patients must have a diagnosis of myeloma

          -  Patients must meet one of the following criteria:

               1. Myeloma has relapsed, progressed, or failed to respond after at least one prior
                  course of therapy (consisting of at least 2 treatment cycles or months of
                  therapy).

               2. Myeloma has responded partially to initial therapy but a complete response
                  (immunofixation negative and normal serum free light chain studies)has NOT
                  developed after a minimum of 3 cycles or months of initial therapy.

               3. Myeloma has high-risk features as defined by the presence of one or more
                  cytogenetic abnormalities known to confer a poor outcome even after standard
                  autotransplants:complex karyotype (> or = to 3
                  abnormalities),t(4;14),t(14;16),del (17)(p13.1),and/or chromosome 13
                  abnormalities.

          -  Patients must have measurable disease on study entry

          -  Patients must be between ages 18-80 (inclusive).

          -  Patients should have adequate vital organ function as defined by the protocol.

          -  ECOG performance status 0-2 (unless due solely to bone pain)

          -  Prior to Lenalidomide maintenance phase, all study participants must be registered
             into the mandatory RevAssist® program, and be willing and able to comply with the
             requirements of RevAssist®.

          -  Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
             test as per the protocol

          -  Lenalidomide treatment phase: able to take aspirin (81 or 325 mg) daily as
             prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low
             molecular weight heparin).

        Exclusion Criteria:

          -  Pregnant or nursing females

          -  HIV or HTLV-1/2 seropositivity

          -  Known history of myelodysplasia

          -  Known history of chronic active hepatitis or liver cirrhosis (if suspected by
             laboratory studies, should be confirmed by liver biopsy).

          -  Active Hepatitis B (as defined by + Hepatitis B surface antigen); + Hepatitis C virus
             (HCV) antibody is NOT an exclusion

          -  Prior autotransplant or allogeneic transplant

          -  More than 4 distinct, prior courses of therapy for myeloma

          -  History of severe autoimmune disease requiring steroids or other immunosuppressive
             treatments.

          -  Active immune-mediated diseases including:connective tissue diseases,
             uveitis,sarcoidosis,inflammatory bowel disease, multiple sclerosis.

          -  Evidence or history of other significant cardiac,hepatic,renal,
             ophthalmologic,psychiatric,or gastrointestinal disease which would likely increase the
             risks of participating in the study

          -  Active bacterial, viral or fungal infections.