Trial of Activated Marrow Infiltrating Lymphocytes Alone or in Conjunction With an Allogeneic Granulocyte Macrophage Colony-stimulating Factor (GM-CSF)-Based Myeloma Cellular Vaccine in the Autologous Transplant Setting in Multiple Myeloma (aMILs)

• Evaluate Progression-free Survival and Overall Survival [ Time Frame: Days 60, 180, and 360 ] [ Designated as safety issue: Yes ]
  Patients will be monitored for progression/relapse on Days 60, 180, and 360, and as clinically indicated. Following one year follow-up, patients will be followed annually for the next four years.
• Anti-tumor immune response [ Time Frame: Days 60, 180, and 360 ] [ Designated as safety issue: No ]
  • Evaluate tumor specific responses in blood and bone marrow
  • Examine T cell responses to DC-pulsed myeloma cell lines
  • Examine induction of novel antibody responses
• The effect of aMILs on osteoclastogenesis [ Time Frame: Days 60, 180, and 360 ] [ Designated as safety issue: No ]

  Parameters of bone turnover that will include:

  • RANKL/OPG ratio
  • Serum C Telopeptide levels
  • bAlkaline phosphatase and osteocalcin
• Effect of aMILs on clonogenic myeloma precursors [ Time Frame: Days 60, 180, and 360 ] [ Designated as safety issue: No ]
  • Examine side population of CD19 enriched PBLs throughout study.

• Progression-free and overall survival [ Designated as safety issue: Yes ]
• Anti-tumor immune response [ Designated as safety issue: No ]
• The effect of aMILs on osteoclastogenesis [ Designated as safety issue: No ]
• Effect of aMILs on clonogenic myeloma precursors [ Designated as safety issue: No ]

Patient Population: Patients with active myeloma (Stage II/III) that have completed induction therapy and are eligible for an autologous stem cell transplant.

Number of Patients: Will treat a total of 32 evaluable patients in a 1:1 randomization of aMILs vs aMILs plus vaccine. An evaluable patient is defined as one which has received the activated MILs and is at least 6 months post-transplant.

Study Objectives:

Disease response as determined by the Blade' criteria will be the primary endpoint of the trial at one year.

Additional study endpoints include progression free survival, parameters of T cell reconstitution, anti-tumor immune responses as well as the effect on osteoclastogenesis and clonogenic myeloma precursor cells.

• Biological: aMILs
  Activated marrow infiltrating lymphocytes
• Biological: Allogeneic Myeloma Vaccine
  Allogeneic granulocyte macrophage colony-stimulating factor (GM-CSF)-based myeloma cellular vaccine

• Experimental: 1
  aMILs
  Intervention: Biological: aMILs
• Experimental: 2
  aMILs + allogeneic myeloma vaccine
  Interventions:

  • Biological: aMILs
  • Biological: Allogeneic Myeloma Vaccine

Inclusion Criteria:

• Durie-Salmon Stage II or III multiple myeloma
• Newly diagnosed either prior to receiving treatment or having completed induction therapy
• Relapsed myeloma not previously transplanted within the past 5 years
• Measurable serum and/or urine M-protein from prior to induction therapy documented and available. A positive serum free lite assay is acceptable
• Age greater than 18 years old
• ECOG performance status of 0 - 2
• Meet all institutional requirements for autologous stem cell transplantation
• The patient must be able to comprehend and have signed the informed consent

Exclusion Criteria:

• Diagnosis of any of the following plasma cell disorders: POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein] and skin changes) Non-secretory myeloma (no measurable protein on Serum Free Lite Assay)
• Plasma cell leukemia
• Amyloidosis
• Use of corticosteroids (glucocorticoids) within 21 days of pre-transplant vaccine or bone marrow collection
• Use of any myeloma-specific therapy other than lenalidomide within 21 days of pre-transplant vaccine
• In a complete remission at the time of bone marrow collection
• Infection requiring treatment with antibiotics, antifungal, or antiviral agents within seven days of vaccination or bone marrow collection
• Participation in any clinical trial, within four weeks prior to vaccination or bone marrow collection on this trial, which involved an investigational drug or device
• History of malignancy other than multiple myeloma within five years of vaccination or bone marrow collection, except adequately treated basal or squamous cell skin cancer
• Active autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosis) requiring systemic treatment. Hypothyroidism without evidence of Grave's Disease or Hashimoto's thyroiditis is permitted
• Evidence of spinal cord compression at time of transplant