Ignite Creation Date:
2024-05-06 @ 4:01 AM
Last Modification Date:
2024-10-26 @ 11:42 AM
Study NCT ID:
NCT02439476
Status:
COMPLETED
Last Update Posted:
2021-01-20
First Post:
2015-04-27
Brief Title:
Non-interventional Study on Salvage Auto in Relapsed Myeloma
Sponsor:
Association for Training Education and Research in Hematology Immunology and Transplantation
Organization:
Association for Training Education and Research in Hematology Immunology and Transplantation
Study Overview
Official Title:
Non-interventional Study Evaluating Plerixafor-based Mobilization for Salvage Autologous Hematopoietic Stem Cell Transplantation in Relapsed Myeloma
Status:
COMPLETED
Status Verified Date:
2020-05
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:
IFM-2015-03
Brief Summary:
Multiple myeloma MM is an incurable disease that is characterized by the accumulation of clonal plasma cells in the bone marrow While MM patients with relapsed disease may achieve responses to subsequent antimyeloma therapies the duration of response decreases with successive relapses until resistant disease develops Until recently the median survival following relapse after induction therapy was approximately one year The relatively recent US Food and Drug Administration FDA approvals of bortezomib 2003 and combination lenalidomide plus dexamethasone 2006 therapies for the treatment of previously treated MM has provided effective therapeutic options that give patients with relapsed or refractory MM the prospect for a prolongation of overall and progression-free survival times However MM remains an incurable disease A clear unmet medical need still exists for additional novel therapeutic options for the treatment of previously treated MM
Plerixafor reversibly inhibits CXCR4 binding to stromal cell derived factor SDF-1alpha and was recently discovered to be an effective agent to mobilize CD34 cells into the peripheral blood In normal volunteers administering Plerixafor after 4-5 days of G-CSF resulted in a 3-35 fold increase in circulating CD34 cells Two phases 3 studies demonstrated that the combination of G-CSF and Plerixafor is superior to G-CSF alone for mobilizing hematopoietic progenitor cells in front-line or as salvage therapy in patients with multiple myeloma
Nevertheless almost all patients ultimately relapse and no plateau is observed in the survival curves At the time of disease recurrence there is not one standard salvage approach but instead various therapeutic options are available including novel agents-based therapy administered for a fixed duration of time or until progression In the pivotal trial for the approval of bortezomib as monotherapy in relapsed and refractory MM the median PFS was 7 months whereas in the pivotal trials for the approval of lenalidomide in combination with dexamethasone in the same group of patients the median time to progression was approximately 11 months A more recent prospective randomized phase 3 study has shown that a triplet combination of bortezomib thalidomide and dexamethasone VTD achieved superior results compared to thalidomide dexamethasone TD alone in patients relapsing following ASCT with a median time to progression of 195 versus 138 months respectively This study suggests that combinations consisting of both an IMiD and a proteasome inhibitor are a valuable option at the time of relapse
However when a frozen graft is available it is also possible to repeat high-dose therapy in patients who previously responded to the frontline application of high-dose melphalan and ASCT Over time several reports have demonstrated the feasibility of this salvage strategy The majority of data are available from retrospective studies and are based on single-centre experiences with small numbers of selected patients In this setting PFS has been shown to range from 7 to 22 months and the treatment-related mortality TRM was acceptable ranging from 0 to 8 Various prognostic factors for prolonged PFS have been described such as the duration of response to the first high-dose therapy or the number of lines of therapy prior to salvage ASCT
With this background this prospective non-interventional multicentre study will aim to collect data on the feasibility of salvage ASCT using a Plerixafor-based stem cell mobilization in relapsed MM according to Plerixafor label in France
This is a non-interventional study visit will be performed as usual according to each center practices No additional visits will be requested for the study purpose The date for each visit and any data generated must be recorded on the appropriate eCRF
The study will consist of 3 periods
An early screening period
Autologous stem cell mobilization period
High dose melphalan therapy and autologous graft infusion and follow-up for12 months after salvage ASCT Inclusion visit
This visit may occur up to 28 days before Mozobil administration This visit will be performed during the visit of pre-transplant assessment For the pre-transplant assessment the procedures are performed routinely before ASCT even if the patient is not included in the study
Stem cell mobilization phase The stem cell mobilization phase is performed according to standard practice of each participating centre
Follow-up visits High dose melphalan administration and autologous graft infusion will be performed according to each centre standard practice Patients will be followed according to each center practices The follow-up of this non-interventional study will end 12 months after ASCT
Subjects will be enrolled over a 2 years period The total duration of the study will be 36 months
Plerixafor reversibly inhibits CXCR4 binding to stromal cell derived factor SDF-1alpha and was recently discovered to be an effective agent to mobilize CD34 cells into the peripheral blood In normal volunteers administering Plerixafor after 4-5 days of G-CSF resulted in a 3-35 fold increase in circulating CD34 cells Two phases 3 studies demonstrated that the combination of G-CSF and Plerixafor is superior to G-CSF alone for mobilizing hematopoietic progenitor cells in front-line or as salvage therapy in patients with multiple myeloma
Nevertheless almost all patients ultimately relapse and no plateau is observed in the survival curves At the time of disease recurrence there is not one standard salvage approach but instead various therapeutic options are available including novel agents-based therapy administered for a fixed duration of time or until progression In the pivotal trial for the approval of bortezomib as monotherapy in relapsed and refractory MM the median PFS was 7 months whereas in the pivotal trials for the approval of lenalidomide in combination with dexamethasone in the same group of patients the median time to progression was approximately 11 months A more recent prospective randomized phase 3 study has shown that a triplet combination of bortezomib thalidomide and dexamethasone VTD achieved superior results compared to thalidomide dexamethasone TD alone in patients relapsing following ASCT with a median time to progression of 195 versus 138 months respectively This study suggests that combinations consisting of both an IMiD and a proteasome inhibitor are a valuable option at the time of relapse
However when a frozen graft is available it is also possible to repeat high-dose therapy in patients who previously responded to the frontline application of high-dose melphalan and ASCT Over time several reports have demonstrated the feasibility of this salvage strategy The majority of data are available from retrospective studies and are based on single-centre experiences with small numbers of selected patients In this setting PFS has been shown to range from 7 to 22 months and the treatment-related mortality TRM was acceptable ranging from 0 to 8 Various prognostic factors for prolonged PFS have been described such as the duration of response to the first high-dose therapy or the number of lines of therapy prior to salvage ASCT
With this background this prospective non-interventional multicentre study will aim to collect data on the feasibility of salvage ASCT using a Plerixafor-based stem cell mobilization in relapsed MM according to Plerixafor label in France
This is a non-interventional study visit will be performed as usual according to each center practices No additional visits will be requested for the study purpose The date for each visit and any data generated must be recorded on the appropriate eCRF
The study will consist of 3 periods
An early screening period
Autologous stem cell mobilization period
High dose melphalan therapy and autologous graft infusion and follow-up for12 months after salvage ASCT Inclusion visit
This visit may occur up to 28 days before Mozobil administration This visit will be performed during the visit of pre-transplant assessment For the pre-transplant assessment the procedures are performed routinely before ASCT even if the patient is not included in the study
Stem cell mobilization phase The stem cell mobilization phase is performed according to standard practice of each participating centre
Follow-up visits High dose melphalan administration and autologous graft infusion will be performed according to each centre standard practice Patients will be followed according to each center practices The follow-up of this non-interventional study will end 12 months after ASCT
Subjects will be enrolled over a 2 years period The total duration of the study will be 36 months
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None