Ignite Creation Date:
2024-05-05 @ 5:20 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00430118
Status:
COMPLETED
Last Update Posted:
2013-05-29
First Post:
2007-01-30
Brief Title:
Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With Acute Lymphoblastic Leukemia
Sponsor:
University Hospital Schleswig-Holstein
Organization:
University Hospital Schleswig-Holstein
Study Overview
Official Title:
ALL-BFM 2000 Multi-Center Study for the Treatment of Children and Adolescents With Acute Lymphoblastic Leukemia
Status:
COMPLETED
Status Verified Date:
2013-05
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 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 may kill more cancer cells It is not yet known which combination chemotherapy regimen is more effective in treating young patients with acute lymphoblastic leukemia
PURPOSE Thisphase III trial is studying several different combination chemotherapy regimens to compare how well they work in treating young patients with acute lymphoblastic leukemia
PURPOSE Thisphase III trial is studying several different combination chemotherapy regimens to compare how well they work in treating young patients with acute lymphoblastic leukemia
Detailed Description:
OBJECTIVES
Compare the relative efficacy of induction therapy comprising dexamethasone or prednisone in terms of a higher rate of event-free survival EFS and overall survival and a reduced rate of relapse in pediatric patients with intermediate-risk or high-risk acute lymphoblastic leukemia ALL
Compare the relative safety of a reduced-intensity reintensification regimen comprising dexamethasone vincristine cyclophosphamide and anthracyclines vs a standard treatment regimen in pediatric patients with standard-risk ALL identified by fast clearance of leukemic cells
Compare the efficacy of a second delayed reintensification regimen vs standard reintensification therapy in terms of improved EFS in pediatric patients with intermediate-risk ALL
Compare the efficacy of extended reintensification therapy triple reinduction vs standard reintensification therapy intensive pulses and one reintensification in pediatric patients with high-risk ALL
OUTLINE This is a randomized multicenter study
Prednisone prephase therapy Patients receive oral prednisone on days 1-7 and one dose of methotrexate MTX intrathecally IT on day 1
Inductionconsolidation therapy protocol I Patients are randomized to 1 of 2 treatment arms
Arm I closed to accrual as of 6302006 Patients receive prednisone PRED on days 8-28
Arm II closed to accrual as of 6302006 Patients receive dexamethasone DEXA on days 8-28
Patients in both arms also receive vincristine VCR and daunorubicin hydrochloride DNR once weekly in weeks 2-5 asparaginase ASP on days 12-33 cyclophosphamide CPM on days 36 and 64 cytarabine ARA-C in weeks 6-9 mercaptopurine MP on days 36-63 and MTX IT on days 1 12 33 45 and 59
NOTE Patients with CNS disease also receive MTX IT on days 18 and 27
After completion of inductionconsolidation therapy patients are stratified according to risk group based on disease response standard-risk SR group negative minimal residual disease MRD on day 33 and before protocol M day 78 vs high-risk HR group MRD 10-³ on day 78 vs intermediate-risk IR group all nonSRnonHR Patients with SR and IR disease proceed to extracompartment therapy Patients with HR disease proceed to reintensification therapy
NOTE Patients meeting any of the following criteria are placed in the HR group regardless of MRD response Philadelphia chromosome-positive disease BCRABL or t922 translocations t411q11q23 or MLLAF4 prednisone-poor-response 1000 blastsmm³ in the peripheral blood on day 8 after prednisone prephase therapy or no response to study induction therapy M23 at day 33
Extracompartment therapy protocol M Patients receive MP on days 1-56 and MTX on days 8 22 36 and 50
After completion of extracompartment therapy SR and IR patients proceed to reintensification therapy SR patients are randomized to arms I or II IR patients are randomized to arms I or III HR patients who have completed inductionconsolidation therapy are randomized to arms IV or V
Reintensification therapy
Arm I standard reinduction therapy protocol II closed to accrual as of 6302006 SR and IR patients receive DEXA on days 1-22 VCR and doxorubicin hydrochloride DOX in weeks 2-5 ASP on days 8 11 15 and 18 CPM on day 36 ARA-C and thioguanine TG on days 36-49 and MTX IT on days 38 and 45 Patients then proceed to maintenance therapy
NOTE Patients with CNS disease also receive MTX IT on days 1 and 18
Arm II reduced-intensity reinduction therapy protocol III closed to accrual as of 6302006 SR patients receive DEXA on days 1-15 VCR and DOX on days 1 and 8 ASP on days 1 4 8 and 11 CPM on day 15 ARA-C and TG on days 15-28 and MTX IT on days 17 and 24 Patients then proceed to maintenance therapy
NOTE Patients with CNS disease also receive MTX on day 1
Arm III reduced-intensity reinductionsecond delayed reinduction therapy double reintensification therapy closed to accrual as of 6302006 IR patients receive reduced-intensity reintensification therapy as in arm II After a 10-week interim maintenance phase treatment repeats once for a second delayed course of reintensification therapy Patients then proceed to maintenance therapy
Arm IV standard reintensification therapy closed to accrual as of 6302006 HR patients receive two sequences of the following HR therapy elements ie in this order 1 2 3 1 2 3 following reintensification therapy as in arm I Patients then proceed to maintenance therapy
Element HR-1 Patients receive DEXA on days 1-5 VCR on days 1 and 6 ARA-C twice on day 5 MTX and CPM every 12 hours on days 2-4 5 doses ASP on days 6 and 11 and MTXARA-CPRED IT on day 1
Element HR-2 Patients receive DEXA on days 1-5 vindesine on days 1 and 6 DNR on day 5 MTX and ifosfamide every 12 hours on days 2-4 5 doses ASP on days 6 and 11 and MTXARA-CPRED IT on day 1 NOTE HR patients with CNS disease also receive IT therapy on day 5
Element HR-3 Patients receive DEXA on days 1-5 ARA-C every 12 hours on days 1-2 4 doses etoposide five times daily on days 3-5 ASP on days 6 and 11 and MTXARA-CPRED IT on day 1
Arm V extended reintensification therapy triple protocol III closed to accrual as of 6302006 HR patients receive HR therapy elements 3 2 and 1 as in arm IV following reintensification therapy as in arm II repeated the therapy element twice with 4-week interim maintenance phases in between Patients then proceed to maintenance therapy
Interim maintenancemaintenance therapy Patients receive MTX once weekly and MP daily until week 104
Radiotherapy HR patients or patients with T-cell acute lymphoblastic leukemia or CNS disease undergo CNS radiotherapy
PROJECTED ACCRUAL A total of 2000 patients will be accrued for this study
Compare the relative efficacy of induction therapy comprising dexamethasone or prednisone in terms of a higher rate of event-free survival EFS and overall survival and a reduced rate of relapse in pediatric patients with intermediate-risk or high-risk acute lymphoblastic leukemia ALL
Compare the relative safety of a reduced-intensity reintensification regimen comprising dexamethasone vincristine cyclophosphamide and anthracyclines vs a standard treatment regimen in pediatric patients with standard-risk ALL identified by fast clearance of leukemic cells
Compare the efficacy of a second delayed reintensification regimen vs standard reintensification therapy in terms of improved EFS in pediatric patients with intermediate-risk ALL
Compare the efficacy of extended reintensification therapy triple reinduction vs standard reintensification therapy intensive pulses and one reintensification in pediatric patients with high-risk ALL
OUTLINE This is a randomized multicenter study
Prednisone prephase therapy Patients receive oral prednisone on days 1-7 and one dose of methotrexate MTX intrathecally IT on day 1
Inductionconsolidation therapy protocol I Patients are randomized to 1 of 2 treatment arms
Arm I closed to accrual as of 6302006 Patients receive prednisone PRED on days 8-28
Arm II closed to accrual as of 6302006 Patients receive dexamethasone DEXA on days 8-28
Patients in both arms also receive vincristine VCR and daunorubicin hydrochloride DNR once weekly in weeks 2-5 asparaginase ASP on days 12-33 cyclophosphamide CPM on days 36 and 64 cytarabine ARA-C in weeks 6-9 mercaptopurine MP on days 36-63 and MTX IT on days 1 12 33 45 and 59
NOTE Patients with CNS disease also receive MTX IT on days 18 and 27
After completion of inductionconsolidation therapy patients are stratified according to risk group based on disease response standard-risk SR group negative minimal residual disease MRD on day 33 and before protocol M day 78 vs high-risk HR group MRD 10-³ on day 78 vs intermediate-risk IR group all nonSRnonHR Patients with SR and IR disease proceed to extracompartment therapy Patients with HR disease proceed to reintensification therapy
NOTE Patients meeting any of the following criteria are placed in the HR group regardless of MRD response Philadelphia chromosome-positive disease BCRABL or t922 translocations t411q11q23 or MLLAF4 prednisone-poor-response 1000 blastsmm³ in the peripheral blood on day 8 after prednisone prephase therapy or no response to study induction therapy M23 at day 33
Extracompartment therapy protocol M Patients receive MP on days 1-56 and MTX on days 8 22 36 and 50
After completion of extracompartment therapy SR and IR patients proceed to reintensification therapy SR patients are randomized to arms I or II IR patients are randomized to arms I or III HR patients who have completed inductionconsolidation therapy are randomized to arms IV or V
Reintensification therapy
Arm I standard reinduction therapy protocol II closed to accrual as of 6302006 SR and IR patients receive DEXA on days 1-22 VCR and doxorubicin hydrochloride DOX in weeks 2-5 ASP on days 8 11 15 and 18 CPM on day 36 ARA-C and thioguanine TG on days 36-49 and MTX IT on days 38 and 45 Patients then proceed to maintenance therapy
NOTE Patients with CNS disease also receive MTX IT on days 1 and 18
Arm II reduced-intensity reinduction therapy protocol III closed to accrual as of 6302006 SR patients receive DEXA on days 1-15 VCR and DOX on days 1 and 8 ASP on days 1 4 8 and 11 CPM on day 15 ARA-C and TG on days 15-28 and MTX IT on days 17 and 24 Patients then proceed to maintenance therapy
NOTE Patients with CNS disease also receive MTX on day 1
Arm III reduced-intensity reinductionsecond delayed reinduction therapy double reintensification therapy closed to accrual as of 6302006 IR patients receive reduced-intensity reintensification therapy as in arm II After a 10-week interim maintenance phase treatment repeats once for a second delayed course of reintensification therapy Patients then proceed to maintenance therapy
Arm IV standard reintensification therapy closed to accrual as of 6302006 HR patients receive two sequences of the following HR therapy elements ie in this order 1 2 3 1 2 3 following reintensification therapy as in arm I Patients then proceed to maintenance therapy
Element HR-1 Patients receive DEXA on days 1-5 VCR on days 1 and 6 ARA-C twice on day 5 MTX and CPM every 12 hours on days 2-4 5 doses ASP on days 6 and 11 and MTXARA-CPRED IT on day 1
Element HR-2 Patients receive DEXA on days 1-5 vindesine on days 1 and 6 DNR on day 5 MTX and ifosfamide every 12 hours on days 2-4 5 doses ASP on days 6 and 11 and MTXARA-CPRED IT on day 1 NOTE HR patients with CNS disease also receive IT therapy on day 5
Element HR-3 Patients receive DEXA on days 1-5 ARA-C every 12 hours on days 1-2 4 doses etoposide five times daily on days 3-5 ASP on days 6 and 11 and MTXARA-CPRED IT on day 1
Arm V extended reintensification therapy triple protocol III closed to accrual as of 6302006 HR patients receive HR therapy elements 3 2 and 1 as in arm IV following reintensification therapy as in arm II repeated the therapy element twice with 4-week interim maintenance phases in between Patients then proceed to maintenance therapy
Interim maintenancemaintenance therapy Patients receive MTX once weekly and MP daily until week 104
Radiotherapy HR patients or patients with T-cell acute lymphoblastic leukemia or CNS disease undergo CNS radiotherapy
PROJECTED ACCRUAL A total of 2000 patients will be accrued for this study
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 |
|---|---|---|---|
| EU-20682 | None | None | None |
| ALL-BFM-2000 | None | None | None |