Lenalidomide + Azacitidine for Adaptive Immunotherapy -> Auto SCT in Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional

Summary: 
      RATIONALE: Lenalidomide may stimulate the immune system in different ways and stop cancer
      cells from growing. Drugs used in chemotherapy, such as azacitidine, work in different ways
      to stop the growth of cancer cells, either by killing the cells or by stopping them from
      dividing. An autologous stem cell transplant may be able to replace blood-forming cells that
      were destroyed by lenalidomide and azacitidine. Giving autologous lymphocytes after the
      transplant may help destroy any remaining cancer cells.

      PURPOSE: This pilot trial is studying how well giving lenalidomide together with azacitidine
      works when followed by autologous stem cell transplant and autologous lymphocyte infusion in
      treating patients with multiple myeloma.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the feasibility of mobilizing and infusing autologous lymphocytes (ALI)
           following immunomodulatory therapy comprising azacitidine and lenalidomide in patients
           with multiple myeloma.

      Secondary

        -  Determine the ability to proceed with autologous stem cell transplantation in these
           patients.

        -  Determine the complete response rate at 6 months following transplant in patients
           treated with this regimen.

        -  Determine the progression-free survival and overall survival of patients treated with
           this regimen.

        -  Determine the time to progression in patients treated with this regimen.

        -  Monitor the toxicity of post-autologous stem cell infusion of autologous lymphocytes.

        -  Measure the pre- and post-ALI immune response to cancer testis antigens (CTA)
           (CTA-specific Ig and T-cell repertoire).

        -  Study the expression of CTA in multiple myeloma before and after azacitidine therapy.

      OUTLINE:

        -  Immunomodulatory therapy: Patients receive azacitidine subcutaneously on days 1-5 and
           oral lenalidomide on days 6-21. Treatment repeats every 28 days for up to 3 courses in
           the absence of disease progression or unacceptable toxicity.

        -  Lymphapheresis: Patients undergo autologous lymphocyte harvest on day 22 of courses 2
           and 3.

        -  Autologous stem cell transplantation (ASCT): Patients undergo single or tandem ASCT
           using standard protocols.

        -  Autologous lymphocyte infusion (ALI): Patients undergo ALI approximately 28-60 days
           after ASCT.

      Blood samples are collected at baseline and periodically during study for correlative
      laboratory studies, including CTA-specific immune monitoring by RT-PCR, ELISPOT assays, and
      flow cytometry. Tissue samples from bone marrow aspirates are also collected at baseline,
      during course one, and after course three for CTA expression and methylation studies.

      After completion of study therapy, patients are followed periodically.
    

Intervention name(s): Azacitidine
Intervention type(s): Drug
Intervention description(s): Subject will receive Vidaza (azacitidine) and Revlimid (lenalidomide) as treatment for their multiple myeloma. The Vidaza will be given for 5 days as an injection. On day 6 they will receive Revlimid taken by mouth every day for 16 days followed by 7 days of rest. The drug cycle will be repeated 0, 1 or 2 more times depending on how their blood counts recover.
Other intervention name(s): Vidaza®; lenalidomide; CC-5013; Revlimid
Intervention MeSH terms: Lenalidomide; Azacitidine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma