Chemotherapy, Stem Cell Transplantation and Donor and Patient Vaccination for Treatment of Multiple Myeloma
Status:
Completed
Trial end date:
2008-01-12
Target enrollment:
Participant gender:
Summary
Background:
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 alloengraftment. Even with a reduction in
treatment related mortality, success with allogeneic SCT is limited by a significant risk of
relapse.
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.
Objectives:
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.
Secondary Objectives:
To evaluate the effect of the Fludarabine-(etoposide, doxorubicin, vincristine, prednisone,
cyclophosphamide) 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.
Eligibility:
Patients 18-75 years of age with Immunoglobulin G (IgG) or Immunoglobulin A (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 human leukocyte antigen (HLA)
antigens.
Design:
Phase 2 trial using a non-myeloablative conditioning regimen to reduce treatment-related
toxicity.
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.