Ignite Creation Date:
2024-05-05 @ 6:50 PM
Last Modification Date:
2024-10-26 @ 9:37 AM
Study NCT ID:
NCT00557193
Status:
COMPLETED
Last Update Posted:
2024-07-15
First Post:
2007-11-09
Brief Title:
Combination Chemotherapy With or Without Lestaurtinib in Treating Younger Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
Sponsor:
Childrens Oncology Group
Organization:
Childrens Oncology Group
Study Overview
Official Title:
A Phase III Study of Risk Directed Therapy for Infants With Acute Lymphoblastic Leukemia ALL Randomization of Highest Risk Infants to Intensive Chemotherapy - FLT3 Inhibition CEP-701 Lestaurtinib NSC617807
Status:
COMPLETED
Status Verified Date:
2024-07
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 phase III trial studies combination chemotherapy with or without lestaurtinib with to see how well they work in treating younger patients with newly diagnosed acute lymphoblastic leukemia Drugs used in chemotherapy work in different ways to stop the growth of stop cancer cells either by killing the cells by stopping them from dividing or by stopping them from spreading Lestaurtinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth It is not yet known whether combination chemotherapy is more effective with or without lestaurtinib in treating acute lymphoblastic leukemia
Detailed Description:
PRIMARY OBJECTIVES
I To estimate the 3-year event-free survival EFS of infants with mixed lineage leukemia-rearranged MLL-R acute lymphoblastic leukemia ALL treated with chemotherapy plus the fms-related tyrosine kinase 3 FLT3 inhibitor lestaurtinib
SECONDARY OBJECTIVES
I To compare the 3-year EFS of infants with MLL-R ALL treated with chemotherapy plus the FLT3 inhibitor lestaurtinib to MLL-R patients treated with chemotherapy alone
II To determine a safe tolerable and biologically active dose of lestaurtinib given in sequential combination with chemotherapy in MLL-R infants
III To characterize the pharmacokinetics and pharmacodynamics of lestaurtinib in infants when given at the proposed dose in sequential combination with chemotherapy
IV To identify molecular mechanisms of resistance to lestaurtinib in leukemic blasts
V To describe levels of minimal residual disease in infants with ALL within the context of the proposed therapy and correlate with outcome
VI To identify gene expression patterns in diagnostic infant leukemia samples that correlate with outcome within the context of the proposed therapy
VII To describe the outcome of infants with MLL-G ALL treated with a modified P9407 chemotherapy backbone that includes an extended continuation phase
OUTLINE
INDUCTION THERAPY WEEKS 1-5 All patients receive induction therapy comprising vincristine sulfate intravenously IV over 1 minute on days 8 15 22 and 29 daunorubicin hydrochloride IV over 30 minutes on days 8 and 9 cyclophosphamide IV over 30 minutes every 12 hours on days 3 and 4 closed as of 051909 pegaspargase or asparaginase intramuscularly IM on days 15 18 22 25 29 and 33 prednisone orally PO thrice daily TID or methylprednisolone IV on days 1-7 dexamethasone IV or PO TID on days 8-28 cytarabine IV over 30 minutes on days 8-21 methotrexate intrathecally IT on days 1 and 29 cytarabine IT on day 15 hydrocortisone IT on days 15 and 29 and filgrastim IV or subcutaneously SC beginning on day 5 and continuing until blood counts recover Standard-risk patients are non-randomly assigned to receive a less intensive chemotherapy regimen without lestaurtinib post-induction therapy A Patients undergo echocardiography ECHO or multigated acquisition scan MUGA blood sample collection and bone marrow biopsy on day 1 week 1
POST-INDUCTION THERAPY A for standard-risk patients MLL-germline G
INDUCTION INTENSIFICATION WEEKS 6-9 Patients receive high-dose methotrexate IV continuously over 24 hours on days 1 and 8 triple IT chemotherapy comprising methotrexate cytarabine and hydrocortisone on days 1 and 8 leucovorin calcium IV or PO every 6 hours beginning 42 hours after start of high-dose methotrexate and continuing until methotrexate level is 01 uM cyclophosphamide IV over 30 minutes on days 15-19 etoposide IV over 2 hours on days 15-19 and filgrastim IV or SC beginning on day 20 and continuing until blood counts recover Patients in morphologic remission proceed to re-induction therapy Patients may undergo bone marrow biopsy on day 1 week 6
RE-INDUCTION WEEKS 10-12 Patients receive vincristine sulfate IV over 1 minute on days 1 8 and 15 daunorubicin hydrochloride IV over 30 minutes on days 1 and 2 cyclophosphamide IV over 30 minutes every 12 hours on days 3 and 4 pegaspargase or asparaginase IM on day 4 dexamethasone IV or PO twice daily BID on days 1-7 and 15-21 triple IT chemotherapy comprising methotrexate cytarabine and hydrocortisone on days 1 and 15 and filgrastim IV or SC beginning on day 5 and continuing until blood counts recover Patients undergo ECHO or MUGA blood sample collection and bone marrow biopsy on day 1 week 10
CONSOLIDATION WEEKS 13-19 Patients receive high-dose methotrexate IV continuously over 24 hours on days 1 and 8 leucovorin calcium IV every 6 hours beginning 42 hours after start of high-dose methotrexate and continuing until methotrexate level is 01 uM triple IT chemotherapy comprising methotrexate cytarabine and hydrocortisone on day 1 etoposide IV over 2 hours on days 15-19 cyclophosphamide IV over 30 minutes on days 15-19 high-dose cytarabine IV over 3 hours every 12 hours on days 29 and 30 pegaspargase or asparaginase IM on day 30 and filgrastim IV or SC beginning on day 20 and day 31 and continuing until blood counts recover
CONTINUATION I WEEKS 20-41 Patients receive vincristine sulfate IV on day 1 in weeks 20 and 24 dexamethasone IV or PO BID on days 1-5 in weeks 20 and 24 triple IT chemotherapy comprising methotrexate cytarabine and hydrocortisone on day 1 in weeks 20 and 24 methotrexate IV on day 1 in weeks 21-24 and 25-27 etoposide IV over 2 hours on day 1-5 in week 28 cyclophosphamide IV over 30 minutes on days 1-5 in week 28 mercaptopurine PO on days 1-7 in weeks 21-23 and 25-27 and filgrastim SC or IV beginning on day 6 in week 28 and continuing until blood counts recover Patients may undergo bone marrow biopsy on day 1 week 20
CONTINUATION II WEEKS 42-104 Patients receive vincristine sulfate IV on days 1 29 and 57 dexamethasone IV or PO BID on days 1-5 29-33 and 57-61 methotrexate IT on day 1 methotrexate PO on days 8 15 22 36 43 50 64 71 and 78 and mercaptopurine PO on days 8-28 36-56 and 64-84 Treatment repeats every 12 weeks for 2 years from diagnosis
A safetyactivity phase is conducted separately for the intermediate-risk IR and high-risk HR patients to identify a safe tolerable and biologically active dose of lestaurtinib combined with chemotherapy backbone Once a tolerableactive dose of lestaurtinib has been identified for IR patients subsequent IR patients are eligible to proceed to an efficacy phase where they are randomized or non-randomly assigned as of 7162014 to chemotherapy with or without lestaurtinib HR patients separately proceed to the randomized efficacy phase if a tolerableactive dose is identified for the HR stratum IR and HR patients are randomized or non-randomly assigned as of 7162014 to 1 of 2 post-induction therapy regimens post-induction therapy B or C
POST-INDUCTION THERAPY B chemotherapy only for IRHR patients classified as MLL-R age 90 days at diagnosis
INDUCTION INTENSIFICATION WEEKS 6-9 Patients receive high-dose methotrexate leucovorin calcium cyclophosphamide etoposide and filgrastim as in post-induction therapy A induction intensification Patients in morphologic remission proceed to re-induction Patients undergo ECHO or MUGA blood sample collection and bone marrow biopsy on day 1 week 6 Retired as of 7162014
RE-INDUCTION WEEKS 10-12 Patients receive vincristine sulfate daunorubicin hydrochloride cyclophosphamide pegaspargase or asparaginase dexamethasone triple IT chemotherapy and filgrastim as in post-induction therapy A re-induction Patients undergo ECHO or MUGA blood sample collection and bone marrow biopsy on day 1 week 10 Retired as of 7162014
CONSOLIDATION WEEKS 13-19 Patients receive high-dose methotrexate leucovorin calcium triple IT chemotherapy etoposide cyclophosphamide high-dose cytarabine pegaspargase or asparaginase and filgrastim as in post-induction therapy A consolidation Retired as of 7162014
CONTINUATION I WEEKS 20-49 Patients receive vincristine sulfate IV over 1 minute on day 1 in weeks 20 24 33 37 and 46 dexamethasone PO or IV BID on days 1-5 in weeks 20 24 33 37 and 46 triple IT chemotherapy on day 1 in weeks 20 24 33 37 and 46 methotrexate IV on day 1 in weeks 21-23 25-26 and 37-45 mercaptopurine PO on days 1-7 in weeks 21-23 25-26 and 37-45 etoposide IV over 2 hours on days 1-5 in week 27 cyclophosphamide IV over 2 hours on days 1-5 in week 27 high-dose cytarabine IV over 3 hours every 12 hours on days 1 and 2 in week 30 pegaspargase or asparaginase IM on day 2 in week 30 and filgrastim SC or IV beginning on day 3 in weeks 30 and continuing until blood counts recover Patients may undergo bone marrow biopsy on day 1 of weeks 20 33 and 46 Retired as of 7162014
CONTINUATION II WEEKS 50-104 Patients receive vincristine sulfate dexamethasone IT methotrexate methotrexate PO and mercaptopurine PO as in post-induction therapy A continuation II Treatment repeats every 12 weeks for 2 years from diagnosis Retired as of 7162014
POST-INDUCTION THERAPY C chemotherapy and lestaurtinib for IRHR patients classified as MLL-R age 90 days at diagnosis
INDUCTION INTENSIFICATION THERAPY WEEKS 6-9 Patients receive high-dose methotrexate leucovorin calcium cyclophosphamide etoposide and filgrastim as in post-induction therapy B induction intensification Patients also receive lestaurtinib PO BID on days 20-27 Patients in morphologic remission proceed to re-inductionPatients undergo ECHO or MUGA blood sample collection and bone marrow biopsy on day 1 week 6
RE-INDUCTION WEEKS 10-12 Patients receive vincristine sulfate daunorubicin hydrochloride cyclophosphamide pegaspargase or asparaginase dexamethasone triple IT chemotherapy and filgrastim as in post-induction therapy B re-induction Patients also receive lestaurtinib PO on days 5-20 Patients undergo ECHO or MUGA blood sample collection and bone marrow biopsy on day 1 week 10
CONSOLIDATION WEEKS 13-19 Patients receive high-dose methotrexate leucovorin calcium triple IT chemotherapy etoposide cyclophosphamide high-dose cytarabine pegaspargase or asparaginase and filgrastim as in post-induction therapy B consolidation Patients also receive lestaurtinib PO on days 20-27 and 31-42
CONTINUATION I WEEKS 20-49 Patients receive vincristine sulfate dexamethasone triple IT chemotherapy methotrexate mercaptopurine etoposide high-dose cytarabine pegaspargase or asparaginase and filgrastim as in post-induction therapy B continuation I Patients also receive lestaurtinib PO on days 2-6 in weeks 20 and 24 days 27-41 in weeks 27-29 days 45-56 in weeks 30-32 Patients may undergo bone marrow biopsy on day 1 of weeks 20 33 and 46
CONTINUATION II WEEKS 50-104 Patients receive vincristine sulfate dexamethasone IT methotrexate methotrexate PO and mercaptopurine PO as in post-induction therapy B continuation II Treatment repeats every 12 weeks for 2 years from diagnosis
After completion of study treatment all patients are followed up every 1-6 months for 4 years and then annually thereafter
I To estimate the 3-year event-free survival EFS of infants with mixed lineage leukemia-rearranged MLL-R acute lymphoblastic leukemia ALL treated with chemotherapy plus the fms-related tyrosine kinase 3 FLT3 inhibitor lestaurtinib
SECONDARY OBJECTIVES
I To compare the 3-year EFS of infants with MLL-R ALL treated with chemotherapy plus the FLT3 inhibitor lestaurtinib to MLL-R patients treated with chemotherapy alone
II To determine a safe tolerable and biologically active dose of lestaurtinib given in sequential combination with chemotherapy in MLL-R infants
III To characterize the pharmacokinetics and pharmacodynamics of lestaurtinib in infants when given at the proposed dose in sequential combination with chemotherapy
IV To identify molecular mechanisms of resistance to lestaurtinib in leukemic blasts
V To describe levels of minimal residual disease in infants with ALL within the context of the proposed therapy and correlate with outcome
VI To identify gene expression patterns in diagnostic infant leukemia samples that correlate with outcome within the context of the proposed therapy
VII To describe the outcome of infants with MLL-G ALL treated with a modified P9407 chemotherapy backbone that includes an extended continuation phase
OUTLINE
INDUCTION THERAPY WEEKS 1-5 All patients receive induction therapy comprising vincristine sulfate intravenously IV over 1 minute on days 8 15 22 and 29 daunorubicin hydrochloride IV over 30 minutes on days 8 and 9 cyclophosphamide IV over 30 minutes every 12 hours on days 3 and 4 closed as of 051909 pegaspargase or asparaginase intramuscularly IM on days 15 18 22 25 29 and 33 prednisone orally PO thrice daily TID or methylprednisolone IV on days 1-7 dexamethasone IV or PO TID on days 8-28 cytarabine IV over 30 minutes on days 8-21 methotrexate intrathecally IT on days 1 and 29 cytarabine IT on day 15 hydrocortisone IT on days 15 and 29 and filgrastim IV or subcutaneously SC beginning on day 5 and continuing until blood counts recover Standard-risk patients are non-randomly assigned to receive a less intensive chemotherapy regimen without lestaurtinib post-induction therapy A Patients undergo echocardiography ECHO or multigated acquisition scan MUGA blood sample collection and bone marrow biopsy on day 1 week 1
POST-INDUCTION THERAPY A for standard-risk patients MLL-germline G
INDUCTION INTENSIFICATION WEEKS 6-9 Patients receive high-dose methotrexate IV continuously over 24 hours on days 1 and 8 triple IT chemotherapy comprising methotrexate cytarabine and hydrocortisone on days 1 and 8 leucovorin calcium IV or PO every 6 hours beginning 42 hours after start of high-dose methotrexate and continuing until methotrexate level is 01 uM cyclophosphamide IV over 30 minutes on days 15-19 etoposide IV over 2 hours on days 15-19 and filgrastim IV or SC beginning on day 20 and continuing until blood counts recover Patients in morphologic remission proceed to re-induction therapy Patients may undergo bone marrow biopsy on day 1 week 6
RE-INDUCTION WEEKS 10-12 Patients receive vincristine sulfate IV over 1 minute on days 1 8 and 15 daunorubicin hydrochloride IV over 30 minutes on days 1 and 2 cyclophosphamide IV over 30 minutes every 12 hours on days 3 and 4 pegaspargase or asparaginase IM on day 4 dexamethasone IV or PO twice daily BID on days 1-7 and 15-21 triple IT chemotherapy comprising methotrexate cytarabine and hydrocortisone on days 1 and 15 and filgrastim IV or SC beginning on day 5 and continuing until blood counts recover Patients undergo ECHO or MUGA blood sample collection and bone marrow biopsy on day 1 week 10
CONSOLIDATION WEEKS 13-19 Patients receive high-dose methotrexate IV continuously over 24 hours on days 1 and 8 leucovorin calcium IV every 6 hours beginning 42 hours after start of high-dose methotrexate and continuing until methotrexate level is 01 uM triple IT chemotherapy comprising methotrexate cytarabine and hydrocortisone on day 1 etoposide IV over 2 hours on days 15-19 cyclophosphamide IV over 30 minutes on days 15-19 high-dose cytarabine IV over 3 hours every 12 hours on days 29 and 30 pegaspargase or asparaginase IM on day 30 and filgrastim IV or SC beginning on day 20 and day 31 and continuing until blood counts recover
CONTINUATION I WEEKS 20-41 Patients receive vincristine sulfate IV on day 1 in weeks 20 and 24 dexamethasone IV or PO BID on days 1-5 in weeks 20 and 24 triple IT chemotherapy comprising methotrexate cytarabine and hydrocortisone on day 1 in weeks 20 and 24 methotrexate IV on day 1 in weeks 21-24 and 25-27 etoposide IV over 2 hours on day 1-5 in week 28 cyclophosphamide IV over 30 minutes on days 1-5 in week 28 mercaptopurine PO on days 1-7 in weeks 21-23 and 25-27 and filgrastim SC or IV beginning on day 6 in week 28 and continuing until blood counts recover Patients may undergo bone marrow biopsy on day 1 week 20
CONTINUATION II WEEKS 42-104 Patients receive vincristine sulfate IV on days 1 29 and 57 dexamethasone IV or PO BID on days 1-5 29-33 and 57-61 methotrexate IT on day 1 methotrexate PO on days 8 15 22 36 43 50 64 71 and 78 and mercaptopurine PO on days 8-28 36-56 and 64-84 Treatment repeats every 12 weeks for 2 years from diagnosis
A safetyactivity phase is conducted separately for the intermediate-risk IR and high-risk HR patients to identify a safe tolerable and biologically active dose of lestaurtinib combined with chemotherapy backbone Once a tolerableactive dose of lestaurtinib has been identified for IR patients subsequent IR patients are eligible to proceed to an efficacy phase where they are randomized or non-randomly assigned as of 7162014 to chemotherapy with or without lestaurtinib HR patients separately proceed to the randomized efficacy phase if a tolerableactive dose is identified for the HR stratum IR and HR patients are randomized or non-randomly assigned as of 7162014 to 1 of 2 post-induction therapy regimens post-induction therapy B or C
POST-INDUCTION THERAPY B chemotherapy only for IRHR patients classified as MLL-R age 90 days at diagnosis
INDUCTION INTENSIFICATION WEEKS 6-9 Patients receive high-dose methotrexate leucovorin calcium cyclophosphamide etoposide and filgrastim as in post-induction therapy A induction intensification Patients in morphologic remission proceed to re-induction Patients undergo ECHO or MUGA blood sample collection and bone marrow biopsy on day 1 week 6 Retired as of 7162014
RE-INDUCTION WEEKS 10-12 Patients receive vincristine sulfate daunorubicin hydrochloride cyclophosphamide pegaspargase or asparaginase dexamethasone triple IT chemotherapy and filgrastim as in post-induction therapy A re-induction Patients undergo ECHO or MUGA blood sample collection and bone marrow biopsy on day 1 week 10 Retired as of 7162014
CONSOLIDATION WEEKS 13-19 Patients receive high-dose methotrexate leucovorin calcium triple IT chemotherapy etoposide cyclophosphamide high-dose cytarabine pegaspargase or asparaginase and filgrastim as in post-induction therapy A consolidation Retired as of 7162014
CONTINUATION I WEEKS 20-49 Patients receive vincristine sulfate IV over 1 minute on day 1 in weeks 20 24 33 37 and 46 dexamethasone PO or IV BID on days 1-5 in weeks 20 24 33 37 and 46 triple IT chemotherapy on day 1 in weeks 20 24 33 37 and 46 methotrexate IV on day 1 in weeks 21-23 25-26 and 37-45 mercaptopurine PO on days 1-7 in weeks 21-23 25-26 and 37-45 etoposide IV over 2 hours on days 1-5 in week 27 cyclophosphamide IV over 2 hours on days 1-5 in week 27 high-dose cytarabine IV over 3 hours every 12 hours on days 1 and 2 in week 30 pegaspargase or asparaginase IM on day 2 in week 30 and filgrastim SC or IV beginning on day 3 in weeks 30 and continuing until blood counts recover Patients may undergo bone marrow biopsy on day 1 of weeks 20 33 and 46 Retired as of 7162014
CONTINUATION II WEEKS 50-104 Patients receive vincristine sulfate dexamethasone IT methotrexate methotrexate PO and mercaptopurine PO as in post-induction therapy A continuation II Treatment repeats every 12 weeks for 2 years from diagnosis Retired as of 7162014
POST-INDUCTION THERAPY C chemotherapy and lestaurtinib for IRHR patients classified as MLL-R age 90 days at diagnosis
INDUCTION INTENSIFICATION THERAPY WEEKS 6-9 Patients receive high-dose methotrexate leucovorin calcium cyclophosphamide etoposide and filgrastim as in post-induction therapy B induction intensification Patients also receive lestaurtinib PO BID on days 20-27 Patients in morphologic remission proceed to re-inductionPatients undergo ECHO or MUGA blood sample collection and bone marrow biopsy on day 1 week 6
RE-INDUCTION WEEKS 10-12 Patients receive vincristine sulfate daunorubicin hydrochloride cyclophosphamide pegaspargase or asparaginase dexamethasone triple IT chemotherapy and filgrastim as in post-induction therapy B re-induction Patients also receive lestaurtinib PO on days 5-20 Patients undergo ECHO or MUGA blood sample collection and bone marrow biopsy on day 1 week 10
CONSOLIDATION WEEKS 13-19 Patients receive high-dose methotrexate leucovorin calcium triple IT chemotherapy etoposide cyclophosphamide high-dose cytarabine pegaspargase or asparaginase and filgrastim as in post-induction therapy B consolidation Patients also receive lestaurtinib PO on days 20-27 and 31-42
CONTINUATION I WEEKS 20-49 Patients receive vincristine sulfate dexamethasone triple IT chemotherapy methotrexate mercaptopurine etoposide high-dose cytarabine pegaspargase or asparaginase and filgrastim as in post-induction therapy B continuation I Patients also receive lestaurtinib PO on days 2-6 in weeks 20 and 24 days 27-41 in weeks 27-29 days 45-56 in weeks 30-32 Patients may undergo bone marrow biopsy on day 1 of weeks 20 33 and 46
CONTINUATION II WEEKS 50-104 Patients receive vincristine sulfate dexamethasone IT methotrexate methotrexate PO and mercaptopurine PO as in post-induction therapy B continuation II Treatment repeats every 12 weeks for 2 years from diagnosis
After completion of study treatment all patients are followed up every 1-6 months for 4 years 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 |
|---|---|---|---|
| U10CA180886 | NIH | CTEP | httpsreporternihgovquickSearchU10CA180886 |
| NCI-2009-00313 | REGISTRY | None | None |
| CDR0000573996 | None | None | None |
| 08-146 | None | None | None |
| COG-AALL0631 | None | None | None |
| AALL0631 | OTHER | None | None |
| AALL0631 | OTHER | None | None |
| U10CA098543 | NIH | None | None |