Ignite Creation Date:
2024-05-05 @ 11:33 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00075725
Status:
COMPLETED
Last Update Posted:
2021-04-27
First Post:
2004-01-09
Brief Title:
Dexamethasone Compared With Prednisone During Induction Therapy and Methotrexate With or Without Leucovorin During Maintenance Therapy in Treating Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia
Sponsor:
Childrens Oncology Group
Organization:
Childrens Oncology Group
Study Overview
Official Title:
High Risk B-Precursor Acute Lymphoblastic Leukemia ALL
Status:
COMPLETED
Status Verified Date:
2021-04
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:
This randomized phase III trial is studying dexamethasone to see how well it works compared to prednisone during induction therapy This trial is also studying methotrexate and leucovorin calcium to see how well they work compared to methotrexate alone during maintenance therapy in treating patients with newly diagnosed acute lymphoblastic leukemia ALL Drugs used in chemotherapy such as dexamethasone prednisone methotrexate and leucovorin calcium work in different ways to stop cancer cells from dividing so they stop growing or die Giving more than one drug may kill more cancer cells It is not yet known which combination chemotherapy regimen is more effective in treating acute lymphoblastic leukemia
Detailed Description:
OBJECTIVES
I Improve the outcome of children with high-risk acute lymphoblastic leukemia treated with 2 different chemotherapy regimens
II Determine the relative safety and efficacy of dexamethasone given for 14 days vs prednisone given for 28 days during induction
III Determine the relative safety and efficacy of high-dose methotrexate 5gmm2 with leucovorin rescue compared to escalating methotrexate without leucovorin rescue Capizzi I during interim maintenance I
IV Correlate Day 29 minimal residual disease MRD with event-free survival EFS and overall survival OS
V Correlate early marrow response status with day-29 MRD status VI Improve outcome by identifying additional high risk patients by Day 29 MRD for treatment with fully augmented Berlin-Frankfurt-Munster BFM
OUTLINE This is a randomized multicenter study Patients are stratified according to early response slow early response SER vs rapid early response RER Induction therapy Patients are randomized to 1 of 4 treatment arms
ARM I Patients receive cytarabine intrathecally IT on day 1 vincristine intravenously IV and daunorubicin IV on days 1 8 15 and 22 dexamethasone orally PO or IV twice daily BID on days 1-14 methotrexate MTX IT on days 8 and 29 and pegaspargase intramuscularly IM once on day 4 5 or 6
NOTE Patients with CNS3 disease WBC 5mL in cerebrospinal fluid and positive for blasts on cytospin also receive MTX IT on days 15 and 22
ARM II Patients receive induction therapy as in Arm I
ARM III Patients receive cytarabine vincristine daunorubicin and pegaspargase as in Arm I Patients also receive prednisone PO or IV BID on days 1-28 and MTX IT on days 8 and 29
ARM IV Patients receive induction therapy as in Arm III
Patients in all arms are evaluated at day 29 of induction therapy Patients with M3 disease are removed from study Patients with M1 disease and less than 1 minimal residual disease MRD proceed to consolidation therapy beginning on day 36 Patients with M2 disease OR with MI disease and at least 1 MRD receive extended induction therapy for 2 additional weeks Patients with SER disease and MLL rearrangements are removed from the study but may be eligible for treatment on protocol COG-AALL0031
Extended induction therapy Patients continue to receive therapy on the arm to which they were originally randomized
ARMS I and II Patients receive dexamethasone PO or IV BID on days 1-14 vincristine IV on days 1 and 8 daunorubicin IV on day 1 and pegaspargase IM on day 4 5 or 6 and are then reevaluated
ARMS III and IV Patients receive prednisone PO or IV BID on days 1-14 and vincristine daunorubicin and pegaspargase as in Arms I and II and are then reevaluated
Patients on all arms who have M1 disease and less than 1 MRD after extended induction proceed to consolidation therapy and continue as SER patients All other patients are removed from study
Consolidation therapy All patients receive cyclophosphamide IV over 30 minutes on days 1 and 29 cytarabine IV or subcutaneously SC on days 1-4 8-11 29-32 and 36-39 mercaptopurine MP PO on days 1-14 and 29-42 vincristine IV on days 15 22 43 and 50 pegaspargase IM on days 15 and 43 and MTX IT on days 1 8 15 and 22 Patients with testicular disease also receive radiotherapy to the testes
NOTE Patients with CNS3 disease receive MTX on days 1 and 8 only
Interim maintenance therapy I Patients continue to receive treatment on the arm to which they were originally randomized
ARM I escalating-dose MTX Patients receive vincristine IV and escalating-dose MTX IV on days 1 11 21 31 and 41 pegaspargase IM on days 2 and 22 and MTX IT on days 1 and 21
ARM II high-dose MTX Patients receive vincristine IV and high-dose methotrexate IV over 24 hours on days 1 15 29 and 43 MP PO on days 1-56 and IT MTX on days 1 and 29 Patients also receive leucovorin calcium IV every 6 hours for at least 3 doses beginning 42 hours after start of each MTX infusion
ARM III escalating-dose MTX Patients receive interim maintenance I therapy as in Arm I
ARM IV high-dose MTX Patients receive interim maintenance I therapy as in Arm II
DELAYED INTENSIFICATION THERAPY I All patients receive vincristine IV on days 1 8 15 43 and 50 dexamethasone PO or IV BID on days 1 to 21 for patients age 1 to 12 OR on days 1-7 and 15-21 for patients age 13 and over doxorubicin IV on days 1 8 and 15 pegaspargase IM on day 4 5 or 6 AND day 43 cyclophosphamide IV over 30 minutes on day 29 cytarabine IV or SC on days 30-33 and 37-40 thioguanine PO on days 29-42 and MTX IT on days 1 29 and 36After delayed intensification I SER patients proceed to interim maintenance II and delayed intensification II RER patients proceed directly to maintenance
INTERIM MAINTENANCE THERAPY II All patients receive vincristine IV and MTX IV on days 1 11 21 31 and 41 pegaspargase IM on days 2 and 22 and MTX IT on days 1 and 21 Patients then proceed to delayed intensification II
DELAYED INTENSIFICATION THERAPY II All patients receive therapy as in delayed intensification I arm I CNS3 patients also receive radiotherapy for 3-10 days beginning on day 29 All other SER patients patients with MLL rearrangements and some patients pretreated with steroids 48 hours within the week prior to diagnosis receive prophylactic cranial radiotherapy CRT for 8 days beginning on day 29 Patients then proceed to maintenance therapy
MAINTENANCE THERAPY All patients receive vincristine IV on days 1 29 and 57 dexamethasone PO BID on days 1-5 29-33 and 57-61 MP PO on days 1-84 MTX IT on day 1 and MTX PO on days 1 8 15 22 29 36 43 50 57 64 71 and 78
NOTE RER who did not undergo CRT patients also receive MTX IT on day 29 for maintenance courses 1-4
In all arms maintenance therapy repeats every 12 weeks until total duration of therapy is 2 years from the start of interim maintenance I for female patients and 3 years from the start of interim maintenance I for male patients Patients with testicular disease may receive testicular radiotherapy for 8 days during one of the first 3 courses of maintenance therapy Patients are followed monthly for 1 year every 2 months for 1 year every 3 months for 1 year every 6 months for 1 year and then annually thereafter
I Improve the outcome of children with high-risk acute lymphoblastic leukemia treated with 2 different chemotherapy regimens
II Determine the relative safety and efficacy of dexamethasone given for 14 days vs prednisone given for 28 days during induction
III Determine the relative safety and efficacy of high-dose methotrexate 5gmm2 with leucovorin rescue compared to escalating methotrexate without leucovorin rescue Capizzi I during interim maintenance I
IV Correlate Day 29 minimal residual disease MRD with event-free survival EFS and overall survival OS
V Correlate early marrow response status with day-29 MRD status VI Improve outcome by identifying additional high risk patients by Day 29 MRD for treatment with fully augmented Berlin-Frankfurt-Munster BFM
OUTLINE This is a randomized multicenter study Patients are stratified according to early response slow early response SER vs rapid early response RER Induction therapy Patients are randomized to 1 of 4 treatment arms
ARM I Patients receive cytarabine intrathecally IT on day 1 vincristine intravenously IV and daunorubicin IV on days 1 8 15 and 22 dexamethasone orally PO or IV twice daily BID on days 1-14 methotrexate MTX IT on days 8 and 29 and pegaspargase intramuscularly IM once on day 4 5 or 6
NOTE Patients with CNS3 disease WBC 5mL in cerebrospinal fluid and positive for blasts on cytospin also receive MTX IT on days 15 and 22
ARM II Patients receive induction therapy as in Arm I
ARM III Patients receive cytarabine vincristine daunorubicin and pegaspargase as in Arm I Patients also receive prednisone PO or IV BID on days 1-28 and MTX IT on days 8 and 29
ARM IV Patients receive induction therapy as in Arm III
Patients in all arms are evaluated at day 29 of induction therapy Patients with M3 disease are removed from study Patients with M1 disease and less than 1 minimal residual disease MRD proceed to consolidation therapy beginning on day 36 Patients with M2 disease OR with MI disease and at least 1 MRD receive extended induction therapy for 2 additional weeks Patients with SER disease and MLL rearrangements are removed from the study but may be eligible for treatment on protocol COG-AALL0031
Extended induction therapy Patients continue to receive therapy on the arm to which they were originally randomized
ARMS I and II Patients receive dexamethasone PO or IV BID on days 1-14 vincristine IV on days 1 and 8 daunorubicin IV on day 1 and pegaspargase IM on day 4 5 or 6 and are then reevaluated
ARMS III and IV Patients receive prednisone PO or IV BID on days 1-14 and vincristine daunorubicin and pegaspargase as in Arms I and II and are then reevaluated
Patients on all arms who have M1 disease and less than 1 MRD after extended induction proceed to consolidation therapy and continue as SER patients All other patients are removed from study
Consolidation therapy All patients receive cyclophosphamide IV over 30 minutes on days 1 and 29 cytarabine IV or subcutaneously SC on days 1-4 8-11 29-32 and 36-39 mercaptopurine MP PO on days 1-14 and 29-42 vincristine IV on days 15 22 43 and 50 pegaspargase IM on days 15 and 43 and MTX IT on days 1 8 15 and 22 Patients with testicular disease also receive radiotherapy to the testes
NOTE Patients with CNS3 disease receive MTX on days 1 and 8 only
Interim maintenance therapy I Patients continue to receive treatment on the arm to which they were originally randomized
ARM I escalating-dose MTX Patients receive vincristine IV and escalating-dose MTX IV on days 1 11 21 31 and 41 pegaspargase IM on days 2 and 22 and MTX IT on days 1 and 21
ARM II high-dose MTX Patients receive vincristine IV and high-dose methotrexate IV over 24 hours on days 1 15 29 and 43 MP PO on days 1-56 and IT MTX on days 1 and 29 Patients also receive leucovorin calcium IV every 6 hours for at least 3 doses beginning 42 hours after start of each MTX infusion
ARM III escalating-dose MTX Patients receive interim maintenance I therapy as in Arm I
ARM IV high-dose MTX Patients receive interim maintenance I therapy as in Arm II
DELAYED INTENSIFICATION THERAPY I All patients receive vincristine IV on days 1 8 15 43 and 50 dexamethasone PO or IV BID on days 1 to 21 for patients age 1 to 12 OR on days 1-7 and 15-21 for patients age 13 and over doxorubicin IV on days 1 8 and 15 pegaspargase IM on day 4 5 or 6 AND day 43 cyclophosphamide IV over 30 minutes on day 29 cytarabine IV or SC on days 30-33 and 37-40 thioguanine PO on days 29-42 and MTX IT on days 1 29 and 36After delayed intensification I SER patients proceed to interim maintenance II and delayed intensification II RER patients proceed directly to maintenance
INTERIM MAINTENANCE THERAPY II All patients receive vincristine IV and MTX IV on days 1 11 21 31 and 41 pegaspargase IM on days 2 and 22 and MTX IT on days 1 and 21 Patients then proceed to delayed intensification II
DELAYED INTENSIFICATION THERAPY II All patients receive therapy as in delayed intensification I arm I CNS3 patients also receive radiotherapy for 3-10 days beginning on day 29 All other SER patients patients with MLL rearrangements and some patients pretreated with steroids 48 hours within the week prior to diagnosis receive prophylactic cranial radiotherapy CRT for 8 days beginning on day 29 Patients then proceed to maintenance therapy
MAINTENANCE THERAPY All patients receive vincristine IV on days 1 29 and 57 dexamethasone PO BID on days 1-5 29-33 and 57-61 MP PO on days 1-84 MTX IT on day 1 and MTX PO on days 1 8 15 22 29 36 43 50 57 64 71 and 78
NOTE RER who did not undergo CRT patients also receive MTX IT on day 29 for maintenance courses 1-4
In all arms maintenance therapy repeats every 12 weeks until total duration of therapy is 2 years from the start of interim maintenance I for female patients and 3 years from the start of interim maintenance I for male patients Patients with testicular disease may receive testicular radiotherapy for 8 days during one of the first 3 courses of maintenance therapy Patients are followed monthly for 1 year every 2 months for 1 year every 3 months for 1 year every 6 months for 1 year and then annually thereafter
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 |
|---|---|---|---|
| NCI-2009-00301 | REGISTRY | None | None |
| COG-AALL0232 | None | None | None |
| CDR0000349182 | None | None | None |
| 11723 | None | None | None |
| AALL0232 | OTHER | None | None |
| AALL0232 | OTHER | None | None |
| U10CA098543 | NIH | CTEP | httpsreporternihgovquickSearchU10CA098543 |