Ignite Creation Date:
2024-05-05 @ 4:48 PM
Last Modification Date:
2024-10-26 @ 9:24 AM
Study NCT ID:
NCT00310037
Status:
UNKNOWN
Last Update Posted:
2021-08-18
First Post:
2006-03-29
Brief Title:
Bortezomib After Combination Chemotherapy Rituximab and an Autologous Stem Cell Transplant in Treating Patients With Mantle Cell Lymphoma
Sponsor:
Alliance for Clinical Trials in Oncology
Organization:
Alliance for Clinical Trials in Oncology
Study Overview
Official Title:
A Randomized Phase II Trial of Maintenance vs Consolidation Bortezomib Therapy Following Aggressive Chemo-Immunotherapy and Autologous Stem Cell Transplant for Previously Untreated Mantle Cell Lymphoma
Status:
UNKNOWN
Status Verified Date:
2021-08
Last Known Status:
ACTIVE_NOT_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:
This randomized phase II trial studies how well bortezomib works when given after combination chemotherapy rituximab and an autologous stem cell transplant in treating patients with mantle cell lymphoma Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth Drugs used in chemotherapy work in different ways to stop the growth of cancer cells either by killing the cells or by stopping them from dividing Giving more than one drug combination chemotherapy together with an autologous stem cell transplant may allow more chemotherapy to be given so that more cancer cells are killed Monoclonal antibodies such as rituximab can block cancer growth in different ways Some block the ability of cancer cells to grow and spread Others find cancer cells and help kill them or carry cancer-killing substances to them Giving bortezomib after combination chemotherapy monoclonal antibody therapy and an autologous stem cell transplant may kill any remaining cancer cells or keep the cancer from coming back
Detailed Description:
Objectives
Primary Objective
To determine the 18-month progression-free survival PFS in patients with previously untreated mantle cell lymphoma who are treated with aggressive chemo-immunotherapy and autologous stem cell transplant followed by randomization to either maintenance or consolidation bortezomib therapy
Secondary Objectives
To determine the toxicity profiles of maintenance and consolidation bortezomib by evaluating the number of patients able to complete all maintenance or consolidation therapy
To determine the complete response rate to intensive chemo-immunotherapy plus maintenance or consolidation bortezomib
To determine time to progression and overall survival using these two treatment regimens
CorrelativeOther Pre-Specified Objectives
To determine the importance of p53 mutation or deletion on patient outcome with respect to CR rate PFS and OS
To determine the importance of Ki67 cyclin D1 phosphohistone 3 p27 p21 p16 and PARP p85 expression in pre-treatment tumor biopsies with respect to CR rate PFS and OS
To determine the relationship between proliferation signature and clinical outcome using quantitative real-time RT-PCR
To evaluate the importance of quantitative cyclin D1 expression and expression of cyclin D1 isoforms in predicting clinical outcome using quantitative real-time RT-PCR
To evaluate the prognostic significance of microRNAs in mantle cell lymphoma using microRNA arras
To explore the correlation of selected microRNA polymorphisms with gene target expression with clinical outcomes such as response PFS and OS
To determine changes in gene expression profile from diagnosis to relapse samples to identify genes differentially silenced or over-expressed with disease recurrence
To determine the importance of early PCR negativity following Treatment 2 using bcl-1IgH junction andor IgH chain gene rearrangement with respect to maintained PFS and the success of maintenance or consolidation therapy to converting patients to PCR negative status
OUTLINE OF INTERVENTIONS
CHEMOIMMUNOTHERAPY Patients receive chemoimmunotherapy comprising rituximab intravenously IV over 4-6 hours on day 1 methotrexate MTX IV over 4 hours on day 2 cyclophosphamide IV over 2 hours doxorubicin hydrochloride IV and vincristine sulfate IV on day 3 and prednisone orally PO on days 3-7 Beginning 24 hours after completion of MTX patients receive leucovorin calcium IV every 6 hours until blood levels of MTX are in a safe range Patients also receive filgrastim G-CSF subcutaneously SC once daily QD beginning on day 3 and continuing until blood counts recover Beginning no sooner than day 22 but no later that day 29 of the first course patients receive a second course of chemoimmunotherapy as above Patients with 15 persistent bone marrow involvement may receive a third course of chemoimmunotherapy Patients are restaged and those with progressive disease are removed from therapy
NOTE During the first course of chemoimmunotherapy patients receive rituximab only if the number of circulating mantle cells is 10000mm3 otherwise rituximab is omitted during the first course of chemoimmunotherapy
HIGH-DOSE CONSOLIDATION CHEMOIMMUNOTHERAPY AND PERIPHERAL BLOOD STEM CELL PBSC COLLECTION Approximately 4 weeks after completion of chemoimmunotherapy patients receive high-dose consolidation chemoimmunotherapy comprising cytarabine IV over 2 hours and etoposide phosphate IV continuously on days 1-4 and rituximab IV over 4-6 hours on days 5 and 12 OR 6 and 13 Beginning on day 14 and continuing until completion of PBSC collection patients receive G-CSF SC QD Once blood counts recover patients undergo 1-3 leukapheresis procedures for collection of PBSCs on days 22-25
HIGH-DOSE CHEMOTHERAPY AND AUTOLOGOUS PBSC TRANSPLANTATION PBSCT Beginning 4-6 weeks after completion of leukapheresis patients receive carmustine IV over 2 hours on day -6 etoposide phosphate IV over 4 hours on day -4 and cyclophosphamide IV over 2 hours on day -2 Patients undergo autologous PBSCT on day 0 Patients also receive G-CSF SC QD beginning on day 4 and continuing until blood counts recover
POST-TRANSPLANTATION IMMUNOTHERAPY Approximately 5 weeks after autologous PBSCT patients receive rituximab IV over 4-6 hours once weekly for 2 weeks Approximately 4 weeks after completion of post-transplantation immunotherapy patients proceed to maintenance therapy or consolidation therapy with bortezomib as described in the Arms section
After completion of study treatment patients are followed every 2 months for 2 years every 6 months for 3 years and then annually for 5 years
Primary Objective
To determine the 18-month progression-free survival PFS in patients with previously untreated mantle cell lymphoma who are treated with aggressive chemo-immunotherapy and autologous stem cell transplant followed by randomization to either maintenance or consolidation bortezomib therapy
Secondary Objectives
To determine the toxicity profiles of maintenance and consolidation bortezomib by evaluating the number of patients able to complete all maintenance or consolidation therapy
To determine the complete response rate to intensive chemo-immunotherapy plus maintenance or consolidation bortezomib
To determine time to progression and overall survival using these two treatment regimens
CorrelativeOther Pre-Specified Objectives
To determine the importance of p53 mutation or deletion on patient outcome with respect to CR rate PFS and OS
To determine the importance of Ki67 cyclin D1 phosphohistone 3 p27 p21 p16 and PARP p85 expression in pre-treatment tumor biopsies with respect to CR rate PFS and OS
To determine the relationship between proliferation signature and clinical outcome using quantitative real-time RT-PCR
To evaluate the importance of quantitative cyclin D1 expression and expression of cyclin D1 isoforms in predicting clinical outcome using quantitative real-time RT-PCR
To evaluate the prognostic significance of microRNAs in mantle cell lymphoma using microRNA arras
To explore the correlation of selected microRNA polymorphisms with gene target expression with clinical outcomes such as response PFS and OS
To determine changes in gene expression profile from diagnosis to relapse samples to identify genes differentially silenced or over-expressed with disease recurrence
To determine the importance of early PCR negativity following Treatment 2 using bcl-1IgH junction andor IgH chain gene rearrangement with respect to maintained PFS and the success of maintenance or consolidation therapy to converting patients to PCR negative status
OUTLINE OF INTERVENTIONS
CHEMOIMMUNOTHERAPY Patients receive chemoimmunotherapy comprising rituximab intravenously IV over 4-6 hours on day 1 methotrexate MTX IV over 4 hours on day 2 cyclophosphamide IV over 2 hours doxorubicin hydrochloride IV and vincristine sulfate IV on day 3 and prednisone orally PO on days 3-7 Beginning 24 hours after completion of MTX patients receive leucovorin calcium IV every 6 hours until blood levels of MTX are in a safe range Patients also receive filgrastim G-CSF subcutaneously SC once daily QD beginning on day 3 and continuing until blood counts recover Beginning no sooner than day 22 but no later that day 29 of the first course patients receive a second course of chemoimmunotherapy as above Patients with 15 persistent bone marrow involvement may receive a third course of chemoimmunotherapy Patients are restaged and those with progressive disease are removed from therapy
NOTE During the first course of chemoimmunotherapy patients receive rituximab only if the number of circulating mantle cells is 10000mm3 otherwise rituximab is omitted during the first course of chemoimmunotherapy
HIGH-DOSE CONSOLIDATION CHEMOIMMUNOTHERAPY AND PERIPHERAL BLOOD STEM CELL PBSC COLLECTION Approximately 4 weeks after completion of chemoimmunotherapy patients receive high-dose consolidation chemoimmunotherapy comprising cytarabine IV over 2 hours and etoposide phosphate IV continuously on days 1-4 and rituximab IV over 4-6 hours on days 5 and 12 OR 6 and 13 Beginning on day 14 and continuing until completion of PBSC collection patients receive G-CSF SC QD Once blood counts recover patients undergo 1-3 leukapheresis procedures for collection of PBSCs on days 22-25
HIGH-DOSE CHEMOTHERAPY AND AUTOLOGOUS PBSC TRANSPLANTATION PBSCT Beginning 4-6 weeks after completion of leukapheresis patients receive carmustine IV over 2 hours on day -6 etoposide phosphate IV over 4 hours on day -4 and cyclophosphamide IV over 2 hours on day -2 Patients undergo autologous PBSCT on day 0 Patients also receive G-CSF SC QD beginning on day 4 and continuing until blood counts recover
POST-TRANSPLANTATION IMMUNOTHERAPY Approximately 5 weeks after autologous PBSCT patients receive rituximab IV over 4-6 hours once weekly for 2 weeks Approximately 4 weeks after completion of post-transplantation immunotherapy patients proceed to maintenance therapy or consolidation therapy with bortezomib as described in the Arms section
After completion of study treatment patients are followed every 2 months for 2 years every 6 months for 3 years and then annually for 5 years
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| CDR0000466167 | OTHER | NCI Physician Data Query | None |