Clinical Trial - Active Immunization of Sibling Stem Cell Transplant Donors Against Purified Myeloma Protein of the Stem Cell Recipient with Multiple Myeloma in the Setting of Non-myeloablative, HLA-matched Allogeneic Peripheral Blood Stem Cell Transplantation (CC# 00-C-0201)

Title:	Active Immunization of Sibling Stem Cell Transplant Donors Against Purified Myeloma Protein of the Stem Cell Recipient with Multiple Myeloma in the Setting of Non-myeloablative, HLA-matched Allogeneic Peripheral Blood Stem Cell Transplantation (CC# 00-C-0201)

Phase:	I/II

Purpose:	Primary Objectives: To induce cellular and humoral immunity in allogeneic stem cell donors and recipients against the unique idiotype expressed by the recipient's myeloma. To determine whether antigen-specific immunity, induced in the stem cell donor, can be passively transferred to the allogeneic SCT recipient in the setting of a non-myeloablative conditioning regimen.

Eligibility:	Inclusion Criteria: Patients with IgG or IgA multiple myeloma. Patients who have failed to achieve at least a partial remission following initial conventional chemotherapy regimen or who fail to achieve a complete remission after autologous stem cell transplantation. Patients who have achieved at least a partial remission to conventional chemotherapy will be encouraged to proceed to autologous transplantation, but will also be eligible for this protocol. Patients who are in complete remission are ineligible for this protocol. Patients 18 - 70 years of age. Karnofsky performance status > 80%. LVEF >50%, DLCO >60%, creatinine < 1.5 mg/dl and a creatinine clearance > 50 ml/min, direct bilirubin < 2 mg/dl, SGOT < 4x top normal. Life expectancy > 6 months. Consenting first degree relative matched at 6/6 or 5/6 HLA antigens, this may include a mismatch at the D locus. Ability to give informed consent.

Treatment:	Allogeneic stem cell transplantation (SCT) results in a high percentage of complete remissions, but it can be associated with significant treatment-related mortality, which has been primarily attributed to conventional myeloablative transplant regimens. Recent clinical studies have shown that highly immunosuppressive yet non-myeloablative doses of fludarabine-based chemotherapy can result in alloengraftment. Even with a reduction in treatment-related mortality, success with allogeneic SCT is limited by a significant risk of relapse. The goal of this protocol is to transfer tumor antigen-specific immunity induced in the stem cell donor to the allogeneic SCT recipient to reduce relapse. This would be performed using a non-myeloablative conditioning regimen to reduce treatment-related toxicity. Donors would be immunized with an Id vaccine prepared from the patient. Prior to transplantation patients would receive a conventional chemotherapy regimen which contains agents active in myeloma and is T cell depleting. The allogeneic SCT would be performed with a conditioning regimen consisting of cyclophosphamide and fludarabine. The stem cell source would be blood mobilized with filgrastim, which could potentially enhance the transfer tumor antigen specificity with the larger number of T cells in the allograft as compared to bone marrow. Donor immunization with myeloma Id in the setting of a non-myeloablative may represent a novel strategy for the treatment of multiple myeloma.

Contact:	Bethesda, Maryland National Cancer Institute Experimental Transplantation and Immunology Branch Michael R Bishop, MD Ph: 301-435-2764 Fax: 301-480-4354

Please note: the trials indicated do not include the full inclusion or exclusion criteria. For full protocols, please contact the Principal Investigator (PI) listed.