Ignite Creation Date:
2024-05-05 @ 10:22 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00006184
Status:
COMPLETED
Last Update Posted:
2017-10-20
First Post:
2000-08-23
Brief Title:
Chemotherapy Stem Cell Transplantation and Donor and Patient Vaccination for Treatment of Multiple Myeloma
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official 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
Status:
COMPLETED
Status Verified Date:
2017-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 recipients 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 recipients 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 66 or 56 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
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 recipients 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 recipients 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 66 or 56 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
Detailed Description:
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 allo-engraftment 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 recipients 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-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 recipients 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 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 66 or 56 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
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 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 recipients 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-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 recipients 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 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 66 or 56 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 00-C-0201 | None | None | None |