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
The mainstay of therapy for newly diagnosed multiple myeloma patients remains systemic
chemotherapy. Although partial remissions of up to 60% are obtained with conventional
regimens, multiple myeloma is essentially an incurable disease with a median survival of
approximately 30 months.
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 allo-engraftment. Even with a reduction in
treatment related mortality, success with allogeneic SCT is limited by a significant risk of
Donor immunization with myeloma Id in the setting of a non-myeloablative allogeneic SCT may
represent a novel strategy for the treatment of multiple myeloma.
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
To evaluate the effect of the Fludarabine-EPOCH regimen on host T cell depletion and myeloid
depletion prior to allogeneic SCT.
To determine the efficacy of a novel conventional chemotherapy regimen (Fludarabine-EPOCH)
in the setting multiple myeloma.
To determine the treatment-related morbidity and mortality of allogeneic stem cell
transplantation using a non-myeloablative conditioning regimen in multiple myeloma.
To determine if the re-vaccination of allogeneic stem cell donors with the unique idiotype
expressed by the recipient's myeloma will enhance cellular and humoral immunity to patient
specific-idiotype prior to lymphocyte donation for the treatment of patients with recurrent
or progressive disease after transplantation.
Patients 18-75 years of age with IgG or IgA multiple myeloma.
Patients must have achieved at least a partial remission following initial conventional
chemotherapy regimen or after autologous stem cell transplantation.
Consenting first degree relative matched at 6/6 or 5/6 HLA antigens.
Phase 2 trial using a non-myeloablative conditioning regimen to reduce treatment-related
Recipient will undergo a plasmapheresis to obtain starting material for the isolation of
idiotype protein. 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. Recipients will be immunized with
the Id vaccine following transplantation.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Immune cell depletion is defined as immunosuppression of participants T cells prior to transplant measured by cluster of differentiation 4 (CD4) counts (i.e. cells) > 50 cells per ul.Immune T-cell depletion helps to reduce the ability to reject allogeneic cells in participants and is required for engraftment. Engraftment is the body's ability to accept donor cells.
Claude Sportes, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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