Ignite Creation Date:
2024-05-05 @ 11:40 AM
Last Modification Date:
2024-10-26 @ 9:11 AM
Study NCT ID:
NCT00103285
Status:
COMPLETED
Last Update Posted:
2021-06-14
First Post:
2005-02-07
Brief Title:
Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
Sponsor:
Childrens Oncology Group
Organization:
Childrens Oncology Group
Study Overview
Official Title:
Standard 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 different combination chemotherapy regimens and comparing how well they work in treating patients with newly diagnosed acute lymphoblastic leukemia 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
Detailed Description:
PRIMARY OBJECTIVES
I To determine whether the substitution of three intensified phases of post-Induction treatment for standard phases will improve the event free survival EFS of children with SR-average acute lymphoblastic leukemia ALL
II Determine whether the substitution of intensified Consolidation for standard Consolidation will improve the EFS of children with SR-average ALL
III To determine whether the addition of four doses of percutaneous endoscopic gastrostomy PEG asparaginase given once every three weeks during Consolidation and Interim Maintenance phases will improve the EFS for children with SR-low ALL
SECONDARY OBJECTIVES
I Identify potentially modifiable factors associated with impaired health related quality of life HRQOL at different periods of therapy in the patients who are SR-average enrolled on the standard risk ALL study
II Determine the critical time periods when future intervention studies to mitigate adverse HRQOL outcomes should occur
III Correlate day 29 minimal residual disease MRD with EFS and overall survival OS of patients treated with these regimens
IV Correlate early marrow response with day 29 MRD status V To improve outcome by identifying additional high risk patients by Day 29 MRD for treatment with fully augmented Berlin-Frankfurt-Munster BFM
VI To examine the relative contributions of genetic factors and early treatment response to outcome by comparing the outcome of patients with and without TEL-AML1 fusion or triple trisomy and low levels of MRD at end Induction who are treated with identical therapy on the standard arms of the SR-low and SR-average trials
OUTLINE This is a 2-part partially randomized multicenter study Patients are stratified according to early response to study induction therapy rapid early response standard risk SR-low or SR-average acute lymphoblastic leukemia ALL vs slow early response SR-high ALL After completion of induction therapy but before proceeding to part II therapy patients are assigned to 1 of 3 groups based on stratification
PART I
INDUCTION THERAPY All patients receive cytarabine intrathecally IT on day 1 vincristine IV on days 1 8 15 and 22 dexamethasone IV or orally PO twice daily BID on days 1-28 pegaspargase intramuscularly IM may give IV over 1 to 2 hours on day 4 5 or 6 and methotrexate IT on days 8 and 29 and days 15 and 22 for patients with CNS3 disease Patients with Down syndrome DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT Patients are assessed for response on day 29 Patients with M1 bone marrow AND minimal residual disease MRD 01 OR MRD 01 and 1 proceed to therapy in part II Patients with M2 bone marrow OR M1 bone marrow AND MRD 1 proceed to extended induction therapy Patients with M3 bone marrow are removed from the study
EXTENDED INDUCTION THERAPY Patients receive dexamethasone IV or PO BID on days 1-14 vincristine IV on days 1 and 8 pegaspargase IM on day 4 5 or 6 and daunorubicin hydrochloride IV over 15 minutes to 2 hours on day 1 Patients with M1 bone marrow and MRD 1 after extended induction therapy proceed to therapy in part II Patients with M2 or M3 bone marrow after extended induction therapy are removed from the study
PART II
GROUP 1 SR-low ALL Patients are randomized to 1 of 2 treatment arms
ARM I
STANDARD CONSOLIDATION THERAPY Patients receive vincristine IV on day 1 mercaptopurine PO on days 1-28 and methotrexate IT on days 1 8 and 15 Patients with Down syndrome DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT
STANDARD INTERIM MAINTENANCE THERAPY Patients receive vincristine IV on days 1 and 29 dexamethasone IV or PO BID on days 1-5 and 29-33 mercaptopurine PO on days 1-50 methotrexate PO on days 1 8 15 22 29 36 43 and 50 and methotrexate IT on day 29 Patients with DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT
STANDARD DELAYED INTENSIFICATION DI THERAPY Patients receive vincristine IV on days 1 8 and 15 dexamethasone IV or PO BID on days 1-21 doxorubicin hydrochloride IV over 15 minutes to 2 hours on days 1 8 and 15 pegaspargase IM on day 4 5 or 6 cyclophosphamide IV over 30 minutes on day 29 cytarabine IV or subcutaneously SC on days 29-32 and 36-39 thioguanine PO on days 29-42 and methotrexate IT on days 1 and 29 Patients with DS receive dexamethasone IV or PO BID on days 1-7 and 15-21 and leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT
ARM II
EXPERIMENTAL CONSOLIDATION THERAPY Patients receive vincristine mercaptopurine methotrexate and leucovorin calcium as in arm I and pegaspargase IM on days 1 and 22
EXPERIMENTAL INTERIM MAINTENANCE THERAPY Patients receive vincristine dexamethasone mercaptopurine methotrexate PO and methotrexate IT as in arm I and pegaspargase IM on days 15 and 36Standard DI therapy Patients receive standard DI therapy as in arm I
GROUP 2 SR-average ALL Patients are randomized to 1 of 4 treatment arms
ARM I Patients receive standard consolidation therapy standard interim maintenance therapy and standard DI therapy as in group 1 arm I
ARM II
STANDARD CONSOLIDATION THERAPY Patients receive standard consolidation therapy as in group 1 arm I Augmented interim maintenance therapy Patients receive vincristine IV and methotrexate IV on days 1 11 21 31 and 41 pegaspargase IM on days 2 and 22 and methotrexate IT on days 1 and 31 Patients with DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT Augmented DI therapy Patients receive vincristine IV on days 1 8 15 43 and 50 dexamethasone IV or PO BID on days 1-21 doxorubicin hydrochloride IV over 15 minutes to 2 hours 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 29-32 and 36-39 thioguanine PO on days 29-42 and methotrexate IT on days 1 29 and 36 Patients with DS receive dexamethasone on days 1-7 and 15-21 and leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT
ARM III
INTENSIFIED CONSOLIDATION THERAPY Patients receive cyclophosphamide IV over 30 minutes on days 1 and 29 cytarabine IV or SC on days 1-4 8-11 29-32 and 36-39 mercaptopurine 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 methotrexate IT on days 1 8 15 and 22 Patients with DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT
NOTE Patients with CNS3 disease at diagnosis do not receive methotrexate on days 15 and 22 or leucovorin calcium
STANDARD INTERIM MAINTENANCE THERAPY Patients receive standard interim maintenance therapy as in group 1 arm I
STANDARD DI THERAPY Patients receive standard DI therapy as in group 1 arm I
ARM IV
INTENSIFIED CONSOLIDATION THERAPY Patients receive intensified consolidation therapy as in group 2 arm III
AUGMENTED INTERIM MAINTENANCE THERAPY Patients receive augmented interim maintenance therapy as in group 2 arm II
AUGMENTED DI THERAPY Patients receive augmented DI therapy as in group 2 arm II
GROUP 3 SR-high ALL Patients receive the following therapy Intensified consolidation therapy Patients receive intensified consolidation therapy as in group 2 arm III
AUGMENTED INTERIM MAINTENANCE THERAPY Patients receive augmented interim maintenance therapy as in group 2 arm II Treatment repeats every 56 days for 2 courses
NOTE As of Amendment 7 all SR-High patients currently receiving AIM 1 therapy should complete this phase of therapy and proceed to ADI 1 therapy as originally planned including Capizzi methotrexate during AIM 1 Upon completion of ADI 1 patients should receive a second Interim Maintenance phase with high-dose methotrexate IM HD rather than Capizzi methotrexate Patients should then proceed to ADI 2 and then Maintenance
AUGMENTED DI THERAPY Patients receive augmented DI therapy as in group 2 arm II Treatment repeats every 56 days for 2 courses
NOTE As of Amendment 7 all SR-High patients currently receiving ADI 1 therapy should complete this phase of therapy as originally planned Upon completion of ADI 1 patients should receive a second Interim Maintenance phase with IM HD Patients should then proceed to ADI 2 and then Maintenance
NOTE Patients with CNS3 disease at diagnosis also undergo cranial radiotherapy on days 29-33 and 36-40 during course 2 only these patients do not receive methotrexate on day 36 thioguanine or leucovorin calcium
MAINTENANCE THERAPY All patients receive vincristine IV on days 1 29 and 57 oral dexamethasone twice daily on days 1-5 29-33 and 57-61 oral methotrexate on days 8 15 22 29 36 43 50 57 64 71 and 78 oral mercaptopurine on days 1-84 and methotrexate IT on day 1 Courses repeat every 84 days for a total of 2 years from the start of interim maintenance therapy for female patients and 3 years from the start of interim maintenance therapy for male patients
NOTE SR-High or CNS3 patients should receive up to a maximum of 23 intrathecal treatments for females and 26 intrathecal treatments for males
After the completion of study treatment patients are followed every 1-2 months for 2 years every 3 months for 1 year and then every 6-12 months for 2 years
I To determine whether the substitution of three intensified phases of post-Induction treatment for standard phases will improve the event free survival EFS of children with SR-average acute lymphoblastic leukemia ALL
II Determine whether the substitution of intensified Consolidation for standard Consolidation will improve the EFS of children with SR-average ALL
III To determine whether the addition of four doses of percutaneous endoscopic gastrostomy PEG asparaginase given once every three weeks during Consolidation and Interim Maintenance phases will improve the EFS for children with SR-low ALL
SECONDARY OBJECTIVES
I Identify potentially modifiable factors associated with impaired health related quality of life HRQOL at different periods of therapy in the patients who are SR-average enrolled on the standard risk ALL study
II Determine the critical time periods when future intervention studies to mitigate adverse HRQOL outcomes should occur
III Correlate day 29 minimal residual disease MRD with EFS and overall survival OS of patients treated with these regimens
IV Correlate early marrow response with day 29 MRD status V To improve outcome by identifying additional high risk patients by Day 29 MRD for treatment with fully augmented Berlin-Frankfurt-Munster BFM
VI To examine the relative contributions of genetic factors and early treatment response to outcome by comparing the outcome of patients with and without TEL-AML1 fusion or triple trisomy and low levels of MRD at end Induction who are treated with identical therapy on the standard arms of the SR-low and SR-average trials
OUTLINE This is a 2-part partially randomized multicenter study Patients are stratified according to early response to study induction therapy rapid early response standard risk SR-low or SR-average acute lymphoblastic leukemia ALL vs slow early response SR-high ALL After completion of induction therapy but before proceeding to part II therapy patients are assigned to 1 of 3 groups based on stratification
PART I
INDUCTION THERAPY All patients receive cytarabine intrathecally IT on day 1 vincristine IV on days 1 8 15 and 22 dexamethasone IV or orally PO twice daily BID on days 1-28 pegaspargase intramuscularly IM may give IV over 1 to 2 hours on day 4 5 or 6 and methotrexate IT on days 8 and 29 and days 15 and 22 for patients with CNS3 disease Patients with Down syndrome DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT Patients are assessed for response on day 29 Patients with M1 bone marrow AND minimal residual disease MRD 01 OR MRD 01 and 1 proceed to therapy in part II Patients with M2 bone marrow OR M1 bone marrow AND MRD 1 proceed to extended induction therapy Patients with M3 bone marrow are removed from the study
EXTENDED INDUCTION THERAPY Patients receive dexamethasone IV or PO BID on days 1-14 vincristine IV on days 1 and 8 pegaspargase IM on day 4 5 or 6 and daunorubicin hydrochloride IV over 15 minutes to 2 hours on day 1 Patients with M1 bone marrow and MRD 1 after extended induction therapy proceed to therapy in part II Patients with M2 or M3 bone marrow after extended induction therapy are removed from the study
PART II
GROUP 1 SR-low ALL Patients are randomized to 1 of 2 treatment arms
ARM I
STANDARD CONSOLIDATION THERAPY Patients receive vincristine IV on day 1 mercaptopurine PO on days 1-28 and methotrexate IT on days 1 8 and 15 Patients with Down syndrome DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT
STANDARD INTERIM MAINTENANCE THERAPY Patients receive vincristine IV on days 1 and 29 dexamethasone IV or PO BID on days 1-5 and 29-33 mercaptopurine PO on days 1-50 methotrexate PO on days 1 8 15 22 29 36 43 and 50 and methotrexate IT on day 29 Patients with DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT
STANDARD DELAYED INTENSIFICATION DI THERAPY Patients receive vincristine IV on days 1 8 and 15 dexamethasone IV or PO BID on days 1-21 doxorubicin hydrochloride IV over 15 minutes to 2 hours on days 1 8 and 15 pegaspargase IM on day 4 5 or 6 cyclophosphamide IV over 30 minutes on day 29 cytarabine IV or subcutaneously SC on days 29-32 and 36-39 thioguanine PO on days 29-42 and methotrexate IT on days 1 and 29 Patients with DS receive dexamethasone IV or PO BID on days 1-7 and 15-21 and leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT
ARM II
EXPERIMENTAL CONSOLIDATION THERAPY Patients receive vincristine mercaptopurine methotrexate and leucovorin calcium as in arm I and pegaspargase IM on days 1 and 22
EXPERIMENTAL INTERIM MAINTENANCE THERAPY Patients receive vincristine dexamethasone mercaptopurine methotrexate PO and methotrexate IT as in arm I and pegaspargase IM on days 15 and 36Standard DI therapy Patients receive standard DI therapy as in arm I
GROUP 2 SR-average ALL Patients are randomized to 1 of 4 treatment arms
ARM I Patients receive standard consolidation therapy standard interim maintenance therapy and standard DI therapy as in group 1 arm I
ARM II
STANDARD CONSOLIDATION THERAPY Patients receive standard consolidation therapy as in group 1 arm I Augmented interim maintenance therapy Patients receive vincristine IV and methotrexate IV on days 1 11 21 31 and 41 pegaspargase IM on days 2 and 22 and methotrexate IT on days 1 and 31 Patients with DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT Augmented DI therapy Patients receive vincristine IV on days 1 8 15 43 and 50 dexamethasone IV or PO BID on days 1-21 doxorubicin hydrochloride IV over 15 minutes to 2 hours 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 29-32 and 36-39 thioguanine PO on days 29-42 and methotrexate IT on days 1 29 and 36 Patients with DS receive dexamethasone on days 1-7 and 15-21 and leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT
ARM III
INTENSIFIED CONSOLIDATION THERAPY Patients receive cyclophosphamide IV over 30 minutes on days 1 and 29 cytarabine IV or SC on days 1-4 8-11 29-32 and 36-39 mercaptopurine 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 methotrexate IT on days 1 8 15 and 22 Patients with DS receive leucovorin calcium PO at 48 and 60 hours after each dose of methotrexate IT
NOTE Patients with CNS3 disease at diagnosis do not receive methotrexate on days 15 and 22 or leucovorin calcium
STANDARD INTERIM MAINTENANCE THERAPY Patients receive standard interim maintenance therapy as in group 1 arm I
STANDARD DI THERAPY Patients receive standard DI therapy as in group 1 arm I
ARM IV
INTENSIFIED CONSOLIDATION THERAPY Patients receive intensified consolidation therapy as in group 2 arm III
AUGMENTED INTERIM MAINTENANCE THERAPY Patients receive augmented interim maintenance therapy as in group 2 arm II
AUGMENTED DI THERAPY Patients receive augmented DI therapy as in group 2 arm II
GROUP 3 SR-high ALL Patients receive the following therapy Intensified consolidation therapy Patients receive intensified consolidation therapy as in group 2 arm III
AUGMENTED INTERIM MAINTENANCE THERAPY Patients receive augmented interim maintenance therapy as in group 2 arm II Treatment repeats every 56 days for 2 courses
NOTE As of Amendment 7 all SR-High patients currently receiving AIM 1 therapy should complete this phase of therapy and proceed to ADI 1 therapy as originally planned including Capizzi methotrexate during AIM 1 Upon completion of ADI 1 patients should receive a second Interim Maintenance phase with high-dose methotrexate IM HD rather than Capizzi methotrexate Patients should then proceed to ADI 2 and then Maintenance
AUGMENTED DI THERAPY Patients receive augmented DI therapy as in group 2 arm II Treatment repeats every 56 days for 2 courses
NOTE As of Amendment 7 all SR-High patients currently receiving ADI 1 therapy should complete this phase of therapy as originally planned Upon completion of ADI 1 patients should receive a second Interim Maintenance phase with IM HD Patients should then proceed to ADI 2 and then Maintenance
NOTE Patients with CNS3 disease at diagnosis also undergo cranial radiotherapy on days 29-33 and 36-40 during course 2 only these patients do not receive methotrexate on day 36 thioguanine or leucovorin calcium
MAINTENANCE THERAPY All patients receive vincristine IV on days 1 29 and 57 oral dexamethasone twice daily on days 1-5 29-33 and 57-61 oral methotrexate on days 8 15 22 29 36 43 50 57 64 71 and 78 oral mercaptopurine on days 1-84 and methotrexate IT on day 1 Courses repeat every 84 days for a total of 2 years from the start of interim maintenance therapy for female patients and 3 years from the start of interim maintenance therapy for male patients
NOTE SR-High or CNS3 patients should receive up to a maximum of 23 intrathecal treatments for females and 26 intrathecal treatments for males
After the completion of study treatment patients are followed every 1-2 months for 2 years every 3 months for 1 year and then every 6-12 months for 2 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 |
|---|---|---|---|
| NCI-2009-00302 | REGISTRY | None | None |
| 05-340 | None | None | None |
| COG-AALL0331 | None | None | None |
| CDR0000409589 | None | None | None |
| AALL0331 | OTHER | None | None |
| AALL0331 | OTHER | None | None |
| U10CA098543 | NIH | CTEP | httpsreporternihgovquickSearchU10CA098543 |