Ignite Creation Date:
2024-05-05 @ 11:59 AM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00209222
Status:
UNKNOWN
Last Update Posted:
2012-09-10
First Post:
2005-09-13
Brief Title:
Efficacy of R-CHOP vs R-CHOPR-DHAP in Untreated MCL
Sponsor:
European Mantle Cell Lymphoma Network
Organization:
European Mantle Cell Lymphoma Network
Study Overview
Official Title:
Efficacy of 6x R-CHOP Followed by Myeloablative Radiochemotherapy and Autologous Stem Cell Transplantation vs 3 x R-CHOPR-DHAP Followed by a High Dose ARA-C Containing Myeloablative Regimen and Autologous Stem Cell Transplantation
Status:
UNKNOWN
Status Verified Date:
2009-07
Last Known Status:
RECRUITING
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:
The aim of this study is to determine whether alternating courses of cyclophosphamide doxorubicin vincristine prednisonedexamethasone cytarabine cisplatin CHOPDHAP plus rituximab followed by total body irradiation TBIhigh dose cytarabine ARA-Cmelphalan-peripheral blood stem cell transplantation TAM-PBSCT can improve the time to treatment failure compared to CHOP plus rituximab followed by standard PBSCT dexamethasone carmustine cytarabine etoposide and melphalan Dexa-BEAMTBIhigh dose cyclophosphamide in patients with untreated mantle cell lymphoma
Detailed Description:
Recently a prospective randomized intergroup trial of the European MCL Network has shown that a myeloablative radio-chemotherapy followed by autologous stem cell transplantation PBSCT improves event-free survival EFS when compared to a interferon alpha maintenance therapy after a CHOP-like induction However the CR rate after the CHOP induction was still low 20 Thus several studies have been conducted to increase the CR rate of induction therapy to further improve event-free and overall survival Two recent phase II trials suggest that induction regimens containing high dose Ara-C may significantly improve the CR rate up to 80 In addition a number of studies provide evidence that the humanized anti-CD20 antibody Rituximab may induce significant responses in relapsed MCL A prospective randomized study of the GLSG demonstrated that a combined immuno-chemotherapy CHOP plus Rituximab induces a significantly higher response rate than CHOP alone
The aim of this study is the comparison of the current standard R-CHOP followed by myeloablative radio-chemotherapy and subsequent blood stem cell transplantation to a new alternating induction regimen containing high dose Ara-C R-CHOPDHAP followed by a high dose ARA-C containing myeloablative radio-chemotherapy and PBSCT
This study will be performed as a prospective randomized open-label multicenter phase III trial All patients will be initial randomized for standard treatment versus experimental treatment
REFERENCE ARM
The induction therapy consists of 6 cycles of a CHOP chemotherapy in combination with Rituximab If the mantle cell lymphoma is progressive after 4 cycles of chemotherapy patients will be taken off study Patients achieving at least a partial remission after 6 cycles R-CHOP will proceed to intensified consolidation Dexa-BEAM with stem cell collection and subsequent myelo-ablative radio-chemotherapy TBIHigh Dose Cyclophosphamide with autologous stem cells transplantation
EXPERIMENTAL ARM
Initial cytoreductive chemotherapy comprises of alternating cycles of 3xCHOP and 3x DHAP plus Rituximab Patients with progressive disease after 2 treatment cycles R-CHOP and 2x R-DHAP will be off study Patients achieving at least a partial remission after 3x CHOP and 3x DHAP plus Rituximab will proceed to with stem cell collection The subsequent myeloablative radio-chemotherapy with stem cell transplantation consists of a radiotherapy TBI high dose Ara-C and Melphalan
The primary end point in this study is the time to treatment failure The time to treatment failure will be defined as time from start of initial therapy until first failure A failure will be defined as failure of initial therapy or progression of the lymphoma or death of the patient
Using the data of the PBSCT group in the former European mantle cell study as baseline in a proportional hazard model the improvement for the time to treatment failure expected by the new strategy can be expressed by reduction of relative risk rr A risk reduction to 52 which would correspond to a improvement of 20 in failure free survival after 3 years seems to be a clinical relevant improvement For a working significance level alpha005 and a power of 95 the number of events necessary for a one sided fixed sample trial is about 105 During this study the time to treatment failure will be monitored using an equivalent one-sided triangular sequential test
In order to evaluate the impact of therapy on overall survival in this patients a total follow up of about 12 years for this study is expected
The aim of this study is the comparison of the current standard R-CHOP followed by myeloablative radio-chemotherapy and subsequent blood stem cell transplantation to a new alternating induction regimen containing high dose Ara-C R-CHOPDHAP followed by a high dose ARA-C containing myeloablative radio-chemotherapy and PBSCT
This study will be performed as a prospective randomized open-label multicenter phase III trial All patients will be initial randomized for standard treatment versus experimental treatment
REFERENCE ARM
The induction therapy consists of 6 cycles of a CHOP chemotherapy in combination with Rituximab If the mantle cell lymphoma is progressive after 4 cycles of chemotherapy patients will be taken off study Patients achieving at least a partial remission after 6 cycles R-CHOP will proceed to intensified consolidation Dexa-BEAM with stem cell collection and subsequent myelo-ablative radio-chemotherapy TBIHigh Dose Cyclophosphamide with autologous stem cells transplantation
EXPERIMENTAL ARM
Initial cytoreductive chemotherapy comprises of alternating cycles of 3xCHOP and 3x DHAP plus Rituximab Patients with progressive disease after 2 treatment cycles R-CHOP and 2x R-DHAP will be off study Patients achieving at least a partial remission after 3x CHOP and 3x DHAP plus Rituximab will proceed to with stem cell collection The subsequent myeloablative radio-chemotherapy with stem cell transplantation consists of a radiotherapy TBI high dose Ara-C and Melphalan
The primary end point in this study is the time to treatment failure The time to treatment failure will be defined as time from start of initial therapy until first failure A failure will be defined as failure of initial therapy or progression of the lymphoma or death of the patient
Using the data of the PBSCT group in the former European mantle cell study as baseline in a proportional hazard model the improvement for the time to treatment failure expected by the new strategy can be expressed by reduction of relative risk rr A risk reduction to 52 which would correspond to a improvement of 20 in failure free survival after 3 years seems to be a clinical relevant improvement For a working significance level alpha005 and a power of 95 the number of events necessary for a one sided fixed sample trial is about 105 During this study the time to treatment failure will be monitored using an equivalent one-sided triangular sequential test
In order to evaluate the impact of therapy on overall survival in this patients a total follow up of about 12 years for this study is expected
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