Ignite Creation Date:
2024-05-05 @ 11:26 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00049517
Status:
COMPLETED
Last Update Posted:
2023-06-15
First Post:
2002-11-12
Brief Title:
Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Patients With AML Leukemia
Sponsor:
Eastern Cooperative Oncology Group
Organization:
Eastern Cooperative Oncology Group
Study Overview
Official Title:
A Phase III Trial in Adult Acute Myeloid Leukemia Daunorubicin Dose-Intensification Prior to Risk-Allocated Autologous Stem Cell Transplantation
Status:
COMPLETED
Status Verified Date:
2023-06
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 Giving combination chemotherapy before a stem cell transplant helps stop the growth of cancer cells It also helps stop the patients immune system from rejecting the transplanted stem cells When the healthy stem cells are infused into the patient they may help the patients bone marrow make stem cells red blood cells white blood cells and platelets If the patients stem cells are to be transplanted the patient is also treated with a monoclonal antibody such as gemtuzumab ozogamicin to kill any remaining cancer cells or deliver cancer-killing substances to them without harming normal cells It is not yet known whether combination chemotherapy is more effective with or without gemtuzumab ozogamicin followed by stem cell transplant in treating acute myeloid leukemia
PURPOSE This randomized phase III trial is studying combination chemotherapy gemtuzumab ozogamicin and stem cell transplant to see how well they work compared to combination chemotherapy and peripheral stem cell transplant alone in treating patients with acute myeloid leukemia
PURPOSE This randomized phase III trial is studying combination chemotherapy gemtuzumab ozogamicin and stem cell transplant to see how well they work compared to combination chemotherapy and peripheral stem cell transplant alone in treating patients with acute myeloid leukemia
Detailed Description:
OBJECTIVES
To compare the overall survival OS between two induction regimens standard versus dose intense daunorubicin and cytarabine in patients with de novo AML
To compare disease-free survival DFS between two consolidation regimens
To compare overall survival between two consolidation regimens
OUTLINE This is a randomized multicenter study Patients are stratified according to induction therapy standard-dose daunorubicin vs high-dose daunorubicin
Induction therapy Patients are randomized to 1 of 2 induction arms
Standard Patients receive standard-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7
High dose Patients receive high-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine as in arm I
Patients in both arms may receive a second course of induction therapy if complete remission CR is not achieved after the first course The second course is administered as in arm I to all patients Patients who dont achieve CR after 2 courses of induction therapy are removed from study
Patients who achieve CR after induction therapy proceed to post-remission therapy with EITHER allogeneic transplantation only on or off study OR consolidation therapy and autologous transplantation on study according to risk status and donor status
Patients who are considered at intermediate or high risk for relapse unfavorable cytogeneticshigh WBC and have a suitable related donor undergo an allogeneic transplantation Patients with intermediate-risk cytogenetics WBC no greater than 100000mm3 and appropriate donors have the option of undergoing allogeneic transplantation
Allogeneic transplantation Within 1-3 months after recovery from induction therapy patients receive busulfan IV every 6 hours on days -7 to -4 and cyclophosphamide IV over 4 hours on days -3 and -2 Allogeneic bone marrow or peripheral blood stem cells PBSCs are infused on day 0 Patients receive graft-vs-host disease GVHD prophylaxis comprising cyclosporine IV over 1-4 hours beginning on day -1 and then orally when tolerated twice daily until day 180 Alternatively patients may receive tacrolimus IV over 24 hours beginning on day -1 and then orally twice daily until day 180 Patients also receive methotrexate IV on days 1 3 6 and 11
Patients who do not meet the criteria for allogeneic transplantation ie are favorable risk or do not have a matching related donor or who opt not to undergo allogeneic transplantation proceed to consolidation therapy followed by randomization to 1 of 2 autologous transplantation arms
Consolidation therapy Beginning 2-8 weeks after recovery from induction therapy patients receive high-dose cytarabine IV over 3 hours every 12 hours on days 1 3 and 5 A second course is administered 3 weeks after blood recovery Patients receive filgrastim G-CSF subcutaneously SC daily for 4 days and then autologous PBSCs are harvested by leukapheresis
Autologous stem cell transplantation Patients are randomized to 1 of 2 autologous transplantation arms
Arm I Within 1 month after PBSC collection patients receive conditioning comprising busulfan IV every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2 Patients then undergo autologous PBSC transplantation on day 0 Patients receive sargramostim GM-CSF or G-CSF IV or SC beginning on day 0 and continuing until blood counts recover
Arm II closed to accrual as of 1042007 Within 2-4 weeks after PBSC collection patients receive gemtuzumab ozogamicin IV over 2 hours on day 1 and GM-CSF SC or IV beginning on day 10 and continuing until blood counts recover Within 2-3 weeks after blood count recovery patients receive conditioning and undergo autologous PBSC transplantation as in arm I
Patients are followed monthly for 1 year every 2 months for 1 year and then every 3 months for up to 7 years
ACTUAL ACCRUAL A total of 657 patients were accrued for this study
To compare the overall survival OS between two induction regimens standard versus dose intense daunorubicin and cytarabine in patients with de novo AML
To compare disease-free survival DFS between two consolidation regimens
To compare overall survival between two consolidation regimens
OUTLINE This is a randomized multicenter study Patients are stratified according to induction therapy standard-dose daunorubicin vs high-dose daunorubicin
Induction therapy Patients are randomized to 1 of 2 induction arms
Standard Patients receive standard-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7
High dose Patients receive high-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine as in arm I
Patients in both arms may receive a second course of induction therapy if complete remission CR is not achieved after the first course The second course is administered as in arm I to all patients Patients who dont achieve CR after 2 courses of induction therapy are removed from study
Patients who achieve CR after induction therapy proceed to post-remission therapy with EITHER allogeneic transplantation only on or off study OR consolidation therapy and autologous transplantation on study according to risk status and donor status
Patients who are considered at intermediate or high risk for relapse unfavorable cytogeneticshigh WBC and have a suitable related donor undergo an allogeneic transplantation Patients with intermediate-risk cytogenetics WBC no greater than 100000mm3 and appropriate donors have the option of undergoing allogeneic transplantation
Allogeneic transplantation Within 1-3 months after recovery from induction therapy patients receive busulfan IV every 6 hours on days -7 to -4 and cyclophosphamide IV over 4 hours on days -3 and -2 Allogeneic bone marrow or peripheral blood stem cells PBSCs are infused on day 0 Patients receive graft-vs-host disease GVHD prophylaxis comprising cyclosporine IV over 1-4 hours beginning on day -1 and then orally when tolerated twice daily until day 180 Alternatively patients may receive tacrolimus IV over 24 hours beginning on day -1 and then orally twice daily until day 180 Patients also receive methotrexate IV on days 1 3 6 and 11
Patients who do not meet the criteria for allogeneic transplantation ie are favorable risk or do not have a matching related donor or who opt not to undergo allogeneic transplantation proceed to consolidation therapy followed by randomization to 1 of 2 autologous transplantation arms
Consolidation therapy Beginning 2-8 weeks after recovery from induction therapy patients receive high-dose cytarabine IV over 3 hours every 12 hours on days 1 3 and 5 A second course is administered 3 weeks after blood recovery Patients receive filgrastim G-CSF subcutaneously SC daily for 4 days and then autologous PBSCs are harvested by leukapheresis
Autologous stem cell transplantation Patients are randomized to 1 of 2 autologous transplantation arms
Arm I Within 1 month after PBSC collection patients receive conditioning comprising busulfan IV every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2 Patients then undergo autologous PBSC transplantation on day 0 Patients receive sargramostim GM-CSF or G-CSF IV or SC beginning on day 0 and continuing until blood counts recover
Arm II closed to accrual as of 1042007 Within 2-4 weeks after PBSC collection patients receive gemtuzumab ozogamicin IV over 2 hours on day 1 and GM-CSF SC or IV beginning on day 10 and continuing until blood counts recover Within 2-3 weeks after blood count recovery patients receive conditioning and undergo autologous PBSC transplantation as in arm I
Patients are followed monthly for 1 year every 2 months for 1 year and then every 3 months for up to 7 years
ACTUAL ACCRUAL A total of 657 patients were accrued for this study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U10CA021115 | NIH | None | None |
| E1900 | OTHER | Eastern Cooperative Oncology Group ECOG | httpsreporternihgovquickSearchU10CA021115 |