Ignite Creation Date:
2024-05-06 @ 7:59 AM
Last Modification Date:
2024-10-26 @ 11:55 AM
Study NCT ID:
NCT02646098
Status:
COMPLETED
Last Update Posted:
2024-07-08
First Post:
2015-11-04
Brief Title:
CD34 Selected ASCT for Aggressive Lymphomas
Sponsor:
Insel Gruppe AG University Hospital Bern
Organization:
Insel Gruppe AG University Hospital Bern
Study Overview
Official Title:
CD34 Selected Versus Unselected Autologous Stem Cell Transplantation in Advanced Stage Mantle Cell and Diffuse Large B-cell Lymphoma Patients a Randomized Phase II Study
Status:
COMPLETED
Status Verified Date:
2024-07
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:
SAAL
Brief Summary:
Primary objective
To assess the differences in the overall survival at 3 years of a CD34 cell selection versus no selection of hematopoietic progenitor cells harvested during peripheral blood stem cell collection before high-dose chemotherapy with autologous stem cell transplantation ASCT in advanced stage mantle cell lymphoma MCL or diffuse large B-cell lymphoma DLBCL patients
Secondary objectives
To assess differences in disease-free survival between CD34 cell selection versus no selection of hematopoietic progenitor cells harvested during peripheral blood stem cell collection before high-dose chemotherapy with autologous stem cell transplantation ASCT in advanced stage mantle cell MCL or in diffuse large B-cell lymphoma DLBCL patients
To compare hematologic engraftment and the time needed until hematologic recovery after ASCT using CD34 selected or unselected autologous stem cell grafts
To compare infectious complications particularly CMV infections observed until 100 days after ASCT comparing CD34 selected or unselected autologous stem cell grafts
To assess the response rate at day 100 after ASCT in advanced stage mantle cell lymphoma MCL or diffuse large B-cell lymphoma DLBCL patients after ASCT comparing patients with CD34 cell selection versus no selection
To assess the total time needed for the apheresis procedure and the number of apheresis days needed to ensure the collection of a sufficient number of autologous stem cells comparing patients with CD34 cell selection versus no selection
To assess the need for the additional use of G-CSF Neupogen and of the stem cell releasing compound Plerixafor Mozobil to ensure the collection of a sufficient number of autologous stem cells comparing patients with CD34 cell selection versus no selection
Outcomes
The aim of the study is to show 15 better 3-year overall survival of lymphoma patients having received CD34 cell selection during autologous stem cell collection before autologous stem cell transplantation compared to no CD34 cell selection
To assess the differences in the overall survival at 3 years of a CD34 cell selection versus no selection of hematopoietic progenitor cells harvested during peripheral blood stem cell collection before high-dose chemotherapy with autologous stem cell transplantation ASCT in advanced stage mantle cell lymphoma MCL or diffuse large B-cell lymphoma DLBCL patients
Secondary objectives
To assess differences in disease-free survival between CD34 cell selection versus no selection of hematopoietic progenitor cells harvested during peripheral blood stem cell collection before high-dose chemotherapy with autologous stem cell transplantation ASCT in advanced stage mantle cell MCL or in diffuse large B-cell lymphoma DLBCL patients
To compare hematologic engraftment and the time needed until hematologic recovery after ASCT using CD34 selected or unselected autologous stem cell grafts
To compare infectious complications particularly CMV infections observed until 100 days after ASCT comparing CD34 selected or unselected autologous stem cell grafts
To assess the response rate at day 100 after ASCT in advanced stage mantle cell lymphoma MCL or diffuse large B-cell lymphoma DLBCL patients after ASCT comparing patients with CD34 cell selection versus no selection
To assess the total time needed for the apheresis procedure and the number of apheresis days needed to ensure the collection of a sufficient number of autologous stem cells comparing patients with CD34 cell selection versus no selection
To assess the need for the additional use of G-CSF Neupogen and of the stem cell releasing compound Plerixafor Mozobil to ensure the collection of a sufficient number of autologous stem cells comparing patients with CD34 cell selection versus no selection
Outcomes
The aim of the study is to show 15 better 3-year overall survival of lymphoma patients having received CD34 cell selection during autologous stem cell collection before autologous stem cell transplantation compared to no CD34 cell selection
Detailed Description:
Background and rationale Autologous stem cell transplantation ASCT High-dose chemotherapy HDCT followed by ASCT is considered the treatment of choice for relapsedrefractory lymphomas On the basis of the results of the PARMA study group trial high-dose chemotherapy followed by ASCT has become the standard of care for patients with relapsed chemo-sensitive aggressive lymphoma and it is the treatment of choice in patients relapsing with diffuse large B-cell lymphomas DLBCL mantle cell lymphomas MCL follicular lymphoma FL or Hodgkins disease HD Worldwide about 11000 patients are treated with ASCT per year because of relapsing lymphoma The BEAM chemotherapy regimen is the most frequently used conditioning regimen before ASCT since more than thirty years
Although HDCT with ASCT is a curative strategy for some patients with aggressive non-Hodgkin lymphoma NHL relapse or progression after ASCT is the major limitation of this procedure Together with previously described factors that affect outcome after ASCT - such as prognostic score index clinical response to induction or salvage chemotherapy and the number of chemotherapy regimens received before ASCT - graft contamination with residual lymphoma cells is a major factor for disease relapse
Graft contamination Contamination of autologous graft by residual lymphoma cells has been demonstrated using several techniques including flow cytometry immunohistochemistry or molecular methods Subsequent studies have suggested that contamination with lymphoma cells contributes to relapse after ASCT using mobilized stem cells A better outcome in syngenic transplantation in NHL compared with ASCT suggested the potential clinical benefit of purging the stem cell graft used for SCT
Graft purging The strategies implemented to remove lymphoma cells from harvested peripheral stem cells include complement-mediated use of lymphoma-directed antibodies immunomagnetic beads immunotoxins or chemotherapeutic agents as well as oncolytic viruses Among them CD34 cell selection is an alternative and theoretically attractive strategy for tumor cell removal in lymphomas that do not express the CD34 antigen Various technologies have been used for positive selection of CD34 cells including immunomagnetic bead separation avidin-biotin immunoaffinity systems fluorescence-activated cell sorting and magnetic-activated cell sorting MACS The feasibility and safety of CD34 purified progenitor cell reinfusion after high-dose chemotherapy have also been demonstrated
Clinical use of purged autologous grafts Despite the theoretical advantage of using a purged graft in the ASCT setting the standard procedure for ASCT involves the use of non-selected grafts Whether the use of ex vivo purged grafts with CD34 cell selection translates into improved long-term treatment outcome remains controversial Noteworthy not a single randomized study has been reported so far directly comparing in a prospective manner purged and unpurged grafts in ASCT Thus a randomized prospective direct comparison between these two procedures is long awaited and an unmet clinical need with presumably immediate impact on daily practice of ASCT
Own experience with purged grafts the investigators institution has a long-standing experience with CD34 cell selection applying the CliniMACS device Miltenyi Biotec Bergisch Gladbach Germany The investigator recently summarized the data in a retrospective analysis of advanced stage lymphoma patients comparing 31 patients with CD34 cell selection versus 31 patients without selection including 32 MCL and 30 DLBCL patients Remarkably the investigator found that the 5-year OS for selected versus not selected ASCT patients was 87 and 53 p0004 and the 5-year PFS was 62 and 38 p0031 respectively These retrospective data suggest that using selected autografts for ASCT in advanced stage MCL and DLBCL is associated with significantly longer OS and PFS without increased toxicity infectious complications or impaired engraftment Finally the investigator propose that these data provide the rationale for initiating a prospective randomized study on the use of CD34 cell selection of grafts used for ASCT in patients with advanced-stage aggressive lymphomas
Although HDCT with ASCT is a curative strategy for some patients with aggressive non-Hodgkin lymphoma NHL relapse or progression after ASCT is the major limitation of this procedure Together with previously described factors that affect outcome after ASCT - such as prognostic score index clinical response to induction or salvage chemotherapy and the number of chemotherapy regimens received before ASCT - graft contamination with residual lymphoma cells is a major factor for disease relapse
Graft contamination Contamination of autologous graft by residual lymphoma cells has been demonstrated using several techniques including flow cytometry immunohistochemistry or molecular methods Subsequent studies have suggested that contamination with lymphoma cells contributes to relapse after ASCT using mobilized stem cells A better outcome in syngenic transplantation in NHL compared with ASCT suggested the potential clinical benefit of purging the stem cell graft used for SCT
Graft purging The strategies implemented to remove lymphoma cells from harvested peripheral stem cells include complement-mediated use of lymphoma-directed antibodies immunomagnetic beads immunotoxins or chemotherapeutic agents as well as oncolytic viruses Among them CD34 cell selection is an alternative and theoretically attractive strategy for tumor cell removal in lymphomas that do not express the CD34 antigen Various technologies have been used for positive selection of CD34 cells including immunomagnetic bead separation avidin-biotin immunoaffinity systems fluorescence-activated cell sorting and magnetic-activated cell sorting MACS The feasibility and safety of CD34 purified progenitor cell reinfusion after high-dose chemotherapy have also been demonstrated
Clinical use of purged autologous grafts Despite the theoretical advantage of using a purged graft in the ASCT setting the standard procedure for ASCT involves the use of non-selected grafts Whether the use of ex vivo purged grafts with CD34 cell selection translates into improved long-term treatment outcome remains controversial Noteworthy not a single randomized study has been reported so far directly comparing in a prospective manner purged and unpurged grafts in ASCT Thus a randomized prospective direct comparison between these two procedures is long awaited and an unmet clinical need with presumably immediate impact on daily practice of ASCT
Own experience with purged grafts the investigators institution has a long-standing experience with CD34 cell selection applying the CliniMACS device Miltenyi Biotec Bergisch Gladbach Germany The investigator recently summarized the data in a retrospective analysis of advanced stage lymphoma patients comparing 31 patients with CD34 cell selection versus 31 patients without selection including 32 MCL and 30 DLBCL patients Remarkably the investigator found that the 5-year OS for selected versus not selected ASCT patients was 87 and 53 p0004 and the 5-year PFS was 62 and 38 p0031 respectively These retrospective data suggest that using selected autografts for ASCT in advanced stage MCL and DLBCL is associated with significantly longer OS and PFS without increased toxicity infectious complications or impaired engraftment Finally the investigator propose that these data provide the rationale for initiating a prospective randomized study on the use of CD34 cell selection of grafts used for ASCT in patients with advanced-stage aggressive lymphomas
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
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