Active Immunization of Sibling Bone Marrow Transplant Donors Against Purified Myeloma Protein of the Recipient Undergoing Allogeneic Bone Marrow Transplantation
Active Immunization of Sibling Bone Marrow Transplant Donors Against Purified Myeloma Protein of the Recipient Undergoing Allogeneic Bone Marrow Transplantation
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.
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.
-  INCLUSION CRITERIA:

 Patient Selection:

 Patients with IgG or IgA multiple myeloma who attain at least a PR before transplantation
 are eligible for thsi protocol.

 Patients may only have received 3-4 courses of VAD, high dose cyclophosphamide and one
 autologous transplant before entering the study.

 All previous therapy must be completed at least 2 weeks prior to study entry.

 Patients should have recovered from all hematologic and non-hematologic toxicity of
 previous therapy.

 Steroid must be discontinued at least two weeks prior to vaccination.

 Only patients less than 60 years are eligible for this protocol.

 Patients must meet the following criteria:

 A. Karnofsky performance status greater than or equal to 70 percent.

 B. Life expectancy greater than 8 weeks and absence of co-existing medical problems which
 would significantly increase the risk of the transplant procedure in the judgment of the
 bone marrow transplant attending physicians (e.g., the MUGA left ventricular ejection
 fraction has to be greater than 50% and DLCO greater thant 50% of the expected value when
 corrected for Hb).

 Creatinine less than 2x normal and not rising for at least 2-4 weeks before
 transplantation. If creatinine is elevated, then creatinine clearance must be greater than
 40 ml/min.

 Direct bilirubin less than 2 mg/dl, SGOT less than 4x top normal, and none of these
 parameters increasing, for at least 2-4 weeks before transplantation.

 Patients must be HIV-negative, HBsAg-, and Hepatitis C antibody Negative.

 Not pregnant or lactating. Patients of childbearing potential must use an effective method
 of contraception.

 M-protein concentration in the harvested plasma must be greater than 90 percent of the
 total Ig of the corresponding isotype.

 Patients must be greater than or equal to 18 years old.

 Donor criteria:

 Any consenting healthy individual who fulfills the donor criteria will be considered for
 the marrow donation.

 HLA-identical sibling donors.

 HLA, A and B and DR phenotypically identical family donors.

 HIV, hepatitis B or C seropositive.

 Complete blood count, platelets, and PT, PTT within normal limits.