Ignite Creation Date:
2024-05-05 @ 11:20 AM
Last Modification Date:
2024-10-26 @ 9:03 AM
Study NCT ID:
NCT00002812
Status:
COMPLETED
Last Update Posted:
2013-08-26
First Post:
1999-11-01
Brief Title:
Combination Chemotherapy in Treating Children With Acute Lymphocytic Leukemia
Sponsor:
Childrens Oncology Group
Organization:
Childrens Oncology Group
Study Overview
Official Title:
Treatment of Patients With Acute Lymphoblastic Leukemia With Unfavorable Features A Phase III Group-wide Study
Status:
COMPLETED
Status Verified Date:
2013-08
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 use different ways to stop cancer cells from dividing so they stop growing or die Combining more than one drug and giving the drugs in different combinations may kill more cancer cells
PURPOSE Randomized phase III trial to compare the effectiveness of standard combination chemotherapy treatment with more intensive combination chemotherapy in treating children with acute lymphocytic leukemia
PURPOSE Randomized phase III trial to compare the effectiveness of standard combination chemotherapy treatment with more intensive combination chemotherapy in treating children with acute lymphocytic leukemia
Detailed Description:
OBJECTIVES I Compare the outcomes in children with higher risk acute lymphocytic leukemia ALL treated with postinduction chemotherapy based on marrow response on day 7 of induction therapy for patients with rapid early response M1M2 standard vs intensified consolidation chemotherapy and standard vs prolonged duration of intensification chemotherapy for patients with slow early response addition of doxorubicin vs idarubicin and cyclophosphamide to intensification chemotherapy II Decrease the incidence of avascular necrosis by alternating dexamethasone dosing in patients undergoing 2 courses of delayed intensification III Assess the impact of day 7 marrow status on outcome in these patients IV Determine prognosis more precisely by supplementing presenting clinical features immunophenotype ploidy cytogenetics and early marrow response with BAXBCL-2 ratios pattern of tyrosine kinase activation leukemic burden following induction and intensification therapy and development of high antibody titer to E coli asparaginase V Correlate the traditional prognostic factors of day 7 marrow response immunophenotype ploidy cytogenetics and early marrow response with BAXBCL-2 ratios
OUTLINE This is a partially randomized multicenter study Patients are stratified by center Patients receive one course of the VPLD regimen comprised of vincristine IV and daunorubicin IV over 15 minutes to 2 hours on days 0 and 7 oral prednisone daily on days 0-7 intrathecal cytarabine on day 0 and asparaginase or pegaspargase intramuscularly on days 3 5 and 7 Patients are assigned to 1 of 2 two postinduction chemotherapy groups based on bone marrow response on day 7 of induction Patients with M1M2 marrow on day 7 are considered rapid early responders Patients with M3 marrow on day 7 are considered slow early responders Group 1 Rapid early responders Patients receive 2 additional courses of VPLD induction chemotherapy Patients are then randomized to 1 of 4 treatment arms Arm I Beginning on day 35 of induction therapy patients receive standard Berlin-Frankfurt-Munster BFM regimen with standard delayed intensification Standard BFM for patients in arm I consists of the following consolidation over 5 weeks with cyclophosphamide cytarabine and mercaptopurine interim maintenance over 8 weeks with oral methotrexate and mercaptopurine MTXMP and delayed intensification over 7 weeks consisting of reinduction with vincristine doxorubicin oral dexamethasone and asparaginase or pegaspargase followed by reconsolidation with cyclophosphamide thioguanine and cytarabine Arm II Patients receive standard BFM regimen with double delayed intensification Patients receive therapy similar to those in arm I but dexamethasone is interrupted for 1 week during delayed intensification and the intensification regimen is repeated separated by an 8 week interim maintenance course of oral MTXMP Arm III Patients receive augmented BFM regimen with standard delayed intensification Patients receive 9 weeks of consolidation therapy with 2 courses of vincristine and pegaspargase alternating with the arm I consolidation therapy Vincristine intravenous methotrexate and pegaspargase the Capizzi I regimen are substituted for oral MTXMP in the interim maintenance regimen Pegaspargase is substituted for asparaginase and two additional doses of vincristine are administered during delayed intensification Arm IV Patients receive augmented BFM regimen with double delayed intensification Patients receive intensified chemotherapy throughout combining the additional therapy given to patients in arms II and III Patients receiving augmented BFM regimen receive pegaspargase instead of asparaginase Patients with CNS disease at diagnosis are treated only on arm IV Patients who are Philadelphia chromosome positive and do not have a bone marrow donor are nonrandomly assigned to the treatment group for slow early responders All RER patients receive the same maintenance therapy with vincristineprednisone and oral MTXMP Intrathecal methotrexate is administered periodically throughout protocol treatment Group 2 Slow early responders Patients receive augmented BFM consolidation therapy and Capizzi I interim maintenance identical to that received by rapid early responders in arm IV Patients are then randomized to receive double delayed intensification with either idarubicin or doxorubicin and concurrent cyclophosphamide All patients receive the same maintenance therapy with vincristineprednisone and oral MTXMP Intrathecal MTX is administered periodically throughout protocol treatment Patients with CNS disease at entry receive craniospinal irradiation daily for 5 consecutive days beginning on day 0 of consolidation therapy All slow early responders at diagnosis receive cranial irradiation daily for 5 consecutive days during consolidation therapy Patients with testicular leukemia at diagnosis receive bilateral testicular irradiation daily for 5 consecutive days during consolidation chemotherapy Groups 1 and 2 Maintenance therapy continues for 2 years for girls or 3 years for boys beyond completion of consolidation therapy Patients are followed every 4-6 weeks for 1 year every 3 months for 1 year every 6 months for 2 years and then annually thereafter
PROJECTED ACCRUAL Approximately 1520 patients will be accrued for this study over 4 years
OUTLINE This is a partially randomized multicenter study Patients are stratified by center Patients receive one course of the VPLD regimen comprised of vincristine IV and daunorubicin IV over 15 minutes to 2 hours on days 0 and 7 oral prednisone daily on days 0-7 intrathecal cytarabine on day 0 and asparaginase or pegaspargase intramuscularly on days 3 5 and 7 Patients are assigned to 1 of 2 two postinduction chemotherapy groups based on bone marrow response on day 7 of induction Patients with M1M2 marrow on day 7 are considered rapid early responders Patients with M3 marrow on day 7 are considered slow early responders Group 1 Rapid early responders Patients receive 2 additional courses of VPLD induction chemotherapy Patients are then randomized to 1 of 4 treatment arms Arm I Beginning on day 35 of induction therapy patients receive standard Berlin-Frankfurt-Munster BFM regimen with standard delayed intensification Standard BFM for patients in arm I consists of the following consolidation over 5 weeks with cyclophosphamide cytarabine and mercaptopurine interim maintenance over 8 weeks with oral methotrexate and mercaptopurine MTXMP and delayed intensification over 7 weeks consisting of reinduction with vincristine doxorubicin oral dexamethasone and asparaginase or pegaspargase followed by reconsolidation with cyclophosphamide thioguanine and cytarabine Arm II Patients receive standard BFM regimen with double delayed intensification Patients receive therapy similar to those in arm I but dexamethasone is interrupted for 1 week during delayed intensification and the intensification regimen is repeated separated by an 8 week interim maintenance course of oral MTXMP Arm III Patients receive augmented BFM regimen with standard delayed intensification Patients receive 9 weeks of consolidation therapy with 2 courses of vincristine and pegaspargase alternating with the arm I consolidation therapy Vincristine intravenous methotrexate and pegaspargase the Capizzi I regimen are substituted for oral MTXMP in the interim maintenance regimen Pegaspargase is substituted for asparaginase and two additional doses of vincristine are administered during delayed intensification Arm IV Patients receive augmented BFM regimen with double delayed intensification Patients receive intensified chemotherapy throughout combining the additional therapy given to patients in arms II and III Patients receiving augmented BFM regimen receive pegaspargase instead of asparaginase Patients with CNS disease at diagnosis are treated only on arm IV Patients who are Philadelphia chromosome positive and do not have a bone marrow donor are nonrandomly assigned to the treatment group for slow early responders All RER patients receive the same maintenance therapy with vincristineprednisone and oral MTXMP Intrathecal methotrexate is administered periodically throughout protocol treatment Group 2 Slow early responders Patients receive augmented BFM consolidation therapy and Capizzi I interim maintenance identical to that received by rapid early responders in arm IV Patients are then randomized to receive double delayed intensification with either idarubicin or doxorubicin and concurrent cyclophosphamide All patients receive the same maintenance therapy with vincristineprednisone and oral MTXMP Intrathecal MTX is administered periodically throughout protocol treatment Patients with CNS disease at entry receive craniospinal irradiation daily for 5 consecutive days beginning on day 0 of consolidation therapy All slow early responders at diagnosis receive cranial irradiation daily for 5 consecutive days during consolidation therapy Patients with testicular leukemia at diagnosis receive bilateral testicular irradiation daily for 5 consecutive days during consolidation chemotherapy Groups 1 and 2 Maintenance therapy continues for 2 years for girls or 3 years for boys beyond completion of consolidation therapy Patients are followed every 4-6 weeks for 1 year every 3 months for 1 year every 6 months for 2 years and then annually thereafter
PROJECTED ACCRUAL Approximately 1520 patients will be accrued for this study over 4 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 |
|---|---|---|---|
| CCG-1961 | OTHER | None | None |
| CDR0000064953 | OTHER | Clinical Trialsgov | None |