Active Immunization of Sibling Bone Marrow Transplant Donors Against Purified Myeloma Protein of the Recipient Undergoing Allogeneic Bone Marrow Transplantation
Condition: Graft vs Host Disease; Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Graft vs Host Disease
Study type: Interventional
Phase: Phase 3

Summary: 
      Both patients and marrow donors are treated on Regimen A; patients then proceed to Regimen B.
      The following acronyms are used:

      ABM Allogeneic Bone Marrow

      BU Busulfan, NSC-750

      CF Leucovorin calcium, NSC-3590

      CTX Cyclophosphamide, NSC-26271

      G-CSF Granulocyte Colony-Stimulating Factor (source not specified)

      GM-CSF Granulocyte-Macrophage Colony-Stimulating Factor (Hoechst/Immunex), NSC-613795

      GVHD Graft-vs.-Host Disease

      Mesna Mercaptoethane sulfonate, NSC-113891

      MTX Methotrexate, NSC-740

      PP Unconjugated Myeloma Immunoglobulin plasma paraprotein, NSC-684150

      PP-KLH Myeloma immunoglobulin plasma paraprotein vaccine, NSC-678327, with keyhole limpet
      hemocyanin

      TBI Total-Body Irradiation

      TSPA Thiotepa, NSC-6396

      Regimen A (Donor and Patient): Vaccine Therapy with Immunoadjuvant. PP-KLH (individual
      myeloma immunoglobulin plasma paraprotein vaccine prepared from recipient's plasma
      paraprotein and conjugated with KLH); and PP; with GM-CSF.

      Regimen B (Patient): Myeloablative Radiotherapy and 2-Drug Combination Chemotherapy or 2-Drug
      Combination Myeloablative Chemotherapy followed by Hematopoietic Rescue with Growth Factor
      Support and GVHD Prophylaxis followed by Vaccine Therapy with Immunoadjuvant. TBI; and
      CTX/TSPA; or BU/CTX; followed by ABM; with G-CSF; and CYSP; MTX/CF; followed by PP-KLH; with
      GM-CSF.
    

Detailed description: 
      Multiple Myeloma remains a largely incurable disease with current therapy. Allogeneic bone
      marrow transplantation provides an opportunity to add the potential antitumor effect of
      marrow grafts to those of high dose chemotherapy. One potential strategy for enhancing a
      graft vs. tumor effect without aggravating graft vs. host disease would be to selectively
      target an immune response against a defined tumor-specific antigen. The idiotype of the
      rearranged immunoglobulin gene product of a myeloma can serve as a unique tumor-specific
      antigen for vaccine development. We are testing the hypothesis that tumor antigen-specific
      immunity can be adoptively transferred to BMT recipients by active immunization of marrow
      transplant donors with purified myeloma idiotype protein, conjugated to a carrier protein
      (KLH) and administered with GM-CSF as an immunological adjuvant.

      Patients under age 60 with an HLA-matched sibling donor, with minimal prior treatment,
      defined by less than six months prior chemotherapy, and who are in a minimal residual disease
      state prior to allogeneic BMT, as defined by the achievement of at least a PR, are eligible.
      HLA matched sibling donors receive a series of three vaccinations during an eight week period
      prior to bone marrow harvest. Recipients concurrently receive vaccinations pre-BMT, as well
      as three booster vaccinations at weeks 12, 16, and 24 post-BMT. Id-KLH (0.5 mg) is
      administered s.c. GM-CSF (250 micrograms/m(2)) is administered s.c. locally with the vaccine
      on the day of vaccination and for the three consecutive days following vaccination. The
      objective of this protocol is to induce cellular and humoral immunity in marrow transplant
      donors and recipients against the unique idiotype expressed by the recipient's myeloma.
    

Intervention name(s): Myeloma Immunoglobulin Idiotype Vaccine-KLH; GM-CSF
Intervention type(s): Drug; Drug
Intervention MeSH terms: Immunoglobulins; Immunoglobulins, Intravenous; Antibodies; Immunoglobulin Idiotypes
Primary purpose: Treatment
Keywords: Multiple Myeloma; Vaccine; Idiotype-Specific Immunity; Immune Transfer; Myeloma Immunoglobulin