Ignite Creation Date:
2024-05-05 @ 11:31 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00078949
Status:
COMPLETED
Last Update Posted:
2023-08-23
First Post:
2004-03-08
Brief Title:
Chemotherapy Before Autologous Stem Cell Transplantation - Rituximab in Relapsed or Refractory Aggressive Non-Hodgkins Lymphoma
Sponsor:
NCIC Clinical Trials Group
Organization:
Canadian Cancer Trials Group
Study Overview
Official Title:
Phase III Study Of Gemcitabine Dexamethasone And Cisplatin Compared To Dexamethasone Cytarabine And Cisplatin PlusMinus Rituximab R-GDP vs R-DHAP As Salvage Chemotherapy For Patients With Relapsed Or Refractory Aggressive Histology Non-Hodgkins Lymphoma Prior To Autologous Stem Cell Transplant And Followed By Maintenance Rituximab vs Observation
Status:
COMPLETED
Status Verified Date:
2020-03
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:
RATIONALE Drugs used in chemotherapy such as dexamethasone cisplatin gemcitabine and cytarabine work in different ways to stop cancer cells from dividing so they stop growing or die Combining chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells Giving rituximab as maintenance therapy after stem cell transplantation may kill any remaining cancer cells It is not yet known which salvage chemotherapy regimen is more effective before autologous stem cell transplantation in treating relapsed or refractory non-Hodgkins lymphoma
PURPOSE This randomized phase III trial is studying salvage chemotherapy using dexamethasone cisplatin and gemcitabine to see how well it works compared to dexamethasone cisplatin and cytarabine given before autologous stem cell transplantation in treating patients with relapsed or refractory aggressive non-Hodgkins lymphoma This trial also is studying giving rituximab as maintenance therapy to see how well it works compared to no further therapy after stem cell transplantation Rituximab was added to both salvage treatment arms for CD20 patients in a protocol amendment in 2005
PURPOSE This randomized phase III trial is studying salvage chemotherapy using dexamethasone cisplatin and gemcitabine to see how well it works compared to dexamethasone cisplatin and cytarabine given before autologous stem cell transplantation in treating patients with relapsed or refractory aggressive non-Hodgkins lymphoma This trial also is studying giving rituximab as maintenance therapy to see how well it works compared to no further therapy after stem cell transplantation Rituximab was added to both salvage treatment arms for CD20 patients in a protocol amendment in 2005
Detailed Description:
OBJECTIVES
Salvage therapy
Primary
Compare the response rate and transplantation rate in patients with relapsed or refractory aggressive non-Hodgkins lymphoma when treated with salvage chemotherapy comprising dexamethasone cisplatin and gemcitabine with or without rituximab vs a standard platinum-based regimen dexamethasone cisplatin and high-dose cytarabine with or without rituximab
To compare the transplantation rates of the two protocol salvage regimens
Secondary
Compare the event-free and overall survival of patients treated with these regimens
Compare the success rate of these regimens in terms of getting patients to autologous stem cell transplantation and successful mobilization after high-dose chemotherapy
Compare the quality of life of patients treated with these salvage regimens
Compare the toxic effects of these salvage regimens in these patients
Compare resource utilization for patients treated with these salvage regimens
Compare relative medical and societal costs of these salvage regimens with outcomes in these patients
Maintenance therapy
Primary
Compare the 2-year event-free survival of patients with CD20 B-cell lymphoma treated with maintenance rituximab after these salvage regimens and autologous stem cell transplantation to those patients who received no further treatment
Secondary
Compare the 2-year survival of patients treated with or without maintenance rituximab
Compare the toxic effects of rituximab vs observation alone in these patients
OUTLINE This is a randomized multicenter study For salvage therapy patients are stratified according to participating center International Prognostic Index score at relapsestudy entry 0 or 1 vs 2 vs 3 immunophenotype B cell vs T cell response to or response duration after initial chemotherapy no response or progressive disease vs 1 year vs 1 year and prior rituximab yes vs no For maintenance therapy patients are stratified according to participating center salvage therapy treatment randomization with or without rituximab cisplatin dexamethasone and gemcitabine vs with or without rituximab cisplatin dexamethasone and cytarabine response to salvage therapy complete response CR and CR unconfirmed CRu vs partial response PR vs stable disease SD and prior rituximab yes vs no
Salvage therapy Patients are randomized to 1 of 2 treatment arms
Arm I Patients receive cisplatin IV over 60 minutes on day 1 dexamethasone IV or orally on days 1-4 and gemcitabine IV over 30 minutes on days 1 and 8 Patients with CD20 B cell lymphoma receive rituximab IV over 15-6 hours on day 1
Arm II Patients receive cisplatin IV over 24 hours on day 1 dexamethasone as in arm I and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2 Patients with CD20 B cell lymphoma receive rituximab IV over 15-6 hours on day 1
In both arms treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity
Patients are reassessed after 2 courses Patients with progressive disease are removed from study Patients with a CR CRu or PR proceed to autologous stem cell transplantation ASCT Patients with SD may proceed to ASCT or receive 1 additional course of salvage therapy at the discretion of the investigator Patients receiving an additional course of salvage therapy are then reassessed after the completion of therapy Patients with progressive disease are removed from study Patients with a PR proceed to ASCT Patients with SD may proceed to ASCT or be followed off study at the discretion of the investigator
ASCT Responding patients or those with stable disease if that is the centers policyundergo mobilization stem cell harvest and subsequent ASCT Patients with CD20 B-cell disease are randomized to maintenance therapy or observation
Maintenance therapy Patients are randomized to 1 of 2 treatment arms
Arm I Beginning on day 28 posttransplantation patients receive rituximab IV once every 2 months for 6 doses a total of 12 months in the absence of disease progression or unacceptable toxicity
Arm II Patients undergo observation only Quality of life is assessed at baseline days 1 and 10 of course 2 day 1 of course 3 if given on the last day of salvage therapy or the first day of mobilization if given and at 1 month posttransplantation
Patients who undergo ASCT are followed at months 1 3 7 13 19 and 25 and then annually thereafter Patients who complete salvage therapy but do not undergo ASCT are followed at months 4 8 14 20 and 26 and then annually thereafter Patients who relapse or progress are followed every 6 months until 25 months from ASCT or 26 months from completion of salvage therapy and then annually thereafter
PROJECTED ACCRUAL A total of 637 patients will be accrued for this study within 3-4 years for the first randomization and 240 transplanted CD20 patients will be needed for the second randomization
Salvage therapy
Primary
Compare the response rate and transplantation rate in patients with relapsed or refractory aggressive non-Hodgkins lymphoma when treated with salvage chemotherapy comprising dexamethasone cisplatin and gemcitabine with or without rituximab vs a standard platinum-based regimen dexamethasone cisplatin and high-dose cytarabine with or without rituximab
To compare the transplantation rates of the two protocol salvage regimens
Secondary
Compare the event-free and overall survival of patients treated with these regimens
Compare the success rate of these regimens in terms of getting patients to autologous stem cell transplantation and successful mobilization after high-dose chemotherapy
Compare the quality of life of patients treated with these salvage regimens
Compare the toxic effects of these salvage regimens in these patients
Compare resource utilization for patients treated with these salvage regimens
Compare relative medical and societal costs of these salvage regimens with outcomes in these patients
Maintenance therapy
Primary
Compare the 2-year event-free survival of patients with CD20 B-cell lymphoma treated with maintenance rituximab after these salvage regimens and autologous stem cell transplantation to those patients who received no further treatment
Secondary
Compare the 2-year survival of patients treated with or without maintenance rituximab
Compare the toxic effects of rituximab vs observation alone in these patients
OUTLINE This is a randomized multicenter study For salvage therapy patients are stratified according to participating center International Prognostic Index score at relapsestudy entry 0 or 1 vs 2 vs 3 immunophenotype B cell vs T cell response to or response duration after initial chemotherapy no response or progressive disease vs 1 year vs 1 year and prior rituximab yes vs no For maintenance therapy patients are stratified according to participating center salvage therapy treatment randomization with or without rituximab cisplatin dexamethasone and gemcitabine vs with or without rituximab cisplatin dexamethasone and cytarabine response to salvage therapy complete response CR and CR unconfirmed CRu vs partial response PR vs stable disease SD and prior rituximab yes vs no
Salvage therapy Patients are randomized to 1 of 2 treatment arms
Arm I Patients receive cisplatin IV over 60 minutes on day 1 dexamethasone IV or orally on days 1-4 and gemcitabine IV over 30 minutes on days 1 and 8 Patients with CD20 B cell lymphoma receive rituximab IV over 15-6 hours on day 1
Arm II Patients receive cisplatin IV over 24 hours on day 1 dexamethasone as in arm I and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2 Patients with CD20 B cell lymphoma receive rituximab IV over 15-6 hours on day 1
In both arms treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity
Patients are reassessed after 2 courses Patients with progressive disease are removed from study Patients with a CR CRu or PR proceed to autologous stem cell transplantation ASCT Patients with SD may proceed to ASCT or receive 1 additional course of salvage therapy at the discretion of the investigator Patients receiving an additional course of salvage therapy are then reassessed after the completion of therapy Patients with progressive disease are removed from study Patients with a PR proceed to ASCT Patients with SD may proceed to ASCT or be followed off study at the discretion of the investigator
ASCT Responding patients or those with stable disease if that is the centers policyundergo mobilization stem cell harvest and subsequent ASCT Patients with CD20 B-cell disease are randomized to maintenance therapy or observation
Maintenance therapy Patients are randomized to 1 of 2 treatment arms
Arm I Beginning on day 28 posttransplantation patients receive rituximab IV once every 2 months for 6 doses a total of 12 months in the absence of disease progression or unacceptable toxicity
Arm II Patients undergo observation only Quality of life is assessed at baseline days 1 and 10 of course 2 day 1 of course 3 if given on the last day of salvage therapy or the first day of mobilization if given and at 1 month posttransplantation
Patients who undergo ASCT are followed at months 1 3 7 13 19 and 25 and then annually thereafter Patients who complete salvage therapy but do not undergo ASCT are followed at months 4 8 14 20 and 26 and then annually thereafter Patients who relapse or progress are followed every 6 months until 25 months from ASCT or 26 months from completion of salvage therapy and then annually thereafter
PROJECTED ACCRUAL A total of 637 patients will be accrued for this study within 3-4 years for the first randomization and 240 transplanted CD20 patients will be needed for the second randomization
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 |
|---|---|---|---|
| CDR0000353203 | OTHER | PDQ | None |
| CAN-NCIC-LY12 | None | None | None |