Ignite Creation Date:
2024-05-05 @ 11:23 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00022737
Status:
COMPLETED
Last Update Posted:
2014-02-27
First Post:
2001-08-10
Brief Title:
Combination Chemotherapy With or Without Peripheral Stem Cell Transplant in Treating Children With Acute Lymphoblastic Leukemia
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Childrens Oncology Group Pilot Study for the Treatment of Very High Risk Acute Lymphoblastic Leukemia in Children and Adolescents Imatinib STI571 GLEEVEC NSC716051
Status:
COMPLETED
Status Verified Date:
2012-11
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 II trial is studying how well combination chemotherapy with or without donor peripheral stem cell transplant works in treating children with acute lymphoblastic leukemia Giving combination chemotherapy before a donor peripheral stem cell transplant helps stop the growth of cancer cells It also helps stop the patients immune system from rejecting the donors stem cells When the healthy stem cells from a donor are infused into the patient they may help the patients bone marrow make stem cells red blood cells white blood cells and platelets
Detailed Description:
PRIMARY OBJECTIVES
I Determine the feasibility of treatment with intensified chemotherapy in terms of toxicity and patient accrual in children with very high-risk acute lymphoblastic leukemia
II Determine the feasibility and efficacy of following intensified chemotherapy with allogeneic hematopoietic stem cell transplantation in patients with HLA-matched related donors
III Determine the toxicity of imatinib mesylate in combination with intensified chemotherapy in Philadelphia chromosome-positive patients
IV Determine the event-free survival of patients treated with this regimen V Determine whether minimal residual disease MDR after induction therapy and prior to intensification therapy can predict relapse in these patients
VI Determine whether MDR after intensification is prognostically significant VII Determine whether gene expression patterns predict disease recurrence or response to imatinib mesylate
OUTLINE This is a multicenter study This is also a dose-escalation study of imatinib mesylate in Philadelphia chromosome-positive Ph patients Patients are stratified according to Philadelphia chromosome Ph status Ph-positive vs Ph-negative or indeterminate hypodiploidy yes vs no MLL translocation 11q23 AND slow early response to prior induction therapy yes vs no and failed prior induction therapy yes vs no
Cohorts of 8-12 Ph patients receive escalating doses of imatinib mesylate according to the guidelines for each treatment block of this study until the maximum tolerated dose MTD for each treatment combination is determined The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity An additional 35 patients are treated at the MTD
CONSOLIDATION BLOCK 1 Patients receive etoposide IV over 1 hour followed by ifosfamide IV over 15 hours on days 1-5 Patients also receive methotrexate intrathecally on day 1 and filgrastim G-CSF subcutaneously SC on days 6-15 or until blood counts recover Patients with CNS 23 at diagnosis also receive intrathecal triple therapy comprising methotrexate hydrocortisone and cytarabine ITT on days 8 and 15 Ph patients in cohorts 3 4 and 5 receive oral imatinib mesylate on days 1-21 Within 4 days of starting consolidation therapy patients with biopsy-proven testicular leukemia undergo radiotherapy daily for 12 days
CONSOLIDATION BLOCK 2 Patients receive high-dose methotrexate IV over 24 hours and ITT on day 1 followed by high-dose cytarabine IV over 3 hours every 12 hours on days 2 and 3 Patients also receive leucovorin calcium IV or orally every 6 hours for 3 doses beginning on day 2 and G-CSF SC on days 4-13 or until blood counts recover Ph patients in cohorts 2 3 4 and 5 receive oral imatinib mesylate as in consolidation block 1 Patients undergoing allogeneic hematopoietic stem cell transplantation HSCT proceed to preparative chemotherapy All other patients proceed to reinduction block 1
REINDUCTION BLOCK 1 Patients receive vincristine IV on days 1 8 and 15 daunorubicin IV on days 1 and 2 cyclophosphamide IV over 30 minutes every 12 hours on days 3 and 4 pegaspargase intramuscularly IM on day 4 and ITT on days 1 and 15 Patients also receive oral dexamethasone twice daily on days 1-7 and 15-21 and G-CSF SC on days 5-14 or until blood counts recover Ph patients in cohorts 2 4 and 5 receive imatinib mesylate as in consolidation block 1
INTENSIFICATION BLOCK 1 Patients receive high-dose methotrexate IV over 24 hours on days 1 and 15 and ITT on days 1 and 22 Patients also receive leucovorin calcium IV or orally every 6 hours for 3 doses beginning on days 2 and 16 Patients receive etoposide IV over 2 hours followed by cyclophosphamide IV over 30 minutes on days 22-24 G-CSF SC on days 27-36 or until blood counts recover high-dose cytarabine IV over 3 hours every 12 hours on days 43 and 44 and asparaginase IM on day 44 Ph patients in cohorts 1 and 4 receive oral imatinib mesylate on days 43-63 and patients in cohort 5 receive oral imatinib mesylate on days 1-56
REINDUCTION BLOCK 2 Patients receive vincristine daunorubicin cyclophosphamide pegaspargase dexamethasone and G-CSF as in reinduction block 1 Patients also receive ITT on days 1 and 15 Ph patients receive imatinib mesylate as in reinduction block 1
INTENSIFICATION BLOCK 2 Patients receive methotrexate leucovorin calcium etoposide cyclophosphamide filgrastim cytarabine and asparaginase as in intensification block 1 Ph patients receive imatinib mesylate as in intensification block 1
MAINTENANCE 1 Patients receive high-dose methotrexate IV and leucovorin calcium as in consolidation block 2 Patients also receive ITT and vincristine IV on days 1 and 29 oral dexamethasone twice daily on days 1-5 and 29-33 oral methotrexate on days 8 15 and 22 oral mercaptopurine on days 8-28 etoposide IV over 2 hours followed by cyclophosphamide IV over 30 minutes on days 29-33 and G-CSF SC on days 34-43 Ph patients in cohorts 1-4 receive oral imatinib mesylate on days 29-49 and patients in cohort 5 receive oral imatinib mesylate on days 1-56 Treatment repeats every 8 weeks for 4 courses in the absence of disease progression or unacceptable toxicity
MAINTENANCE 2 Patients receive vincristine and dexamethasone as in maintenance 1 Beginning on day 1 patients undergo cranial radiotherapy once daily 5 days a week for approximately 2 weeks Patients also receive oral methotrexate on days 8 15 22 29 36 43 and 50 and oral mercaptopurine on days 11-56 Ph patients in cohorts 1-4 receive oral imatinib mesylate on days 1-21 and 29-49 and patients in cohort 5 receive oral imatinib mesylate on days 1-56
MAINTENANCE 3 Patients receive vincristine and dexamethasone as in maintenance 2 Patients also receive oral methotrexate on days 1 8 15 22 29 36 43 and 50 and oral mercaptopurine on days 1-56 Ph patients receive imatinib mesylate as in maintenance 2 Treatment repeats every 8 weeks for 7 courses 12 courses total in maintenance 1 2 and 3 in the absence of disease progression or unacceptable toxicity
Patients may undergo allogeneic HSCT after consolidation block 2 if there is an available HLA-DR matched or HLA-A or -B matched or 1 antigen mismatched relative donor
Patients with CNS leukemia undergo cranial radiotherapy 3 times daily on days -10 to -8 All patients undergo radiotherapy twice daily on days -7 to -5 and receive etoposide IV on day -4 and cyclophosphamide IV on days -3 and -2 Patients undergo allogeneic bone marrow peripheral blood stem cell or umbilical cord blood transplantation on day 0 Patients receive cyclosporine IV beginning on day -1 and continuing every 12 hours switching to oral administration when possible until day 60 and tapering thereafter Patients also receive methotrexate on days 1 3 and 6 Beginning 16-24 weeks after transplantation Ph patients receive oral imatinib mesylate once daily for 24 weeks
Patients are followed every 4-8 weeks for 1 year every 3 months for 1 year every 6 months for 1 year and then annually thereafter Patients undergoing HSCT are followed weekly for the first year
I Determine the feasibility of treatment with intensified chemotherapy in terms of toxicity and patient accrual in children with very high-risk acute lymphoblastic leukemia
II Determine the feasibility and efficacy of following intensified chemotherapy with allogeneic hematopoietic stem cell transplantation in patients with HLA-matched related donors
III Determine the toxicity of imatinib mesylate in combination with intensified chemotherapy in Philadelphia chromosome-positive patients
IV Determine the event-free survival of patients treated with this regimen V Determine whether minimal residual disease MDR after induction therapy and prior to intensification therapy can predict relapse in these patients
VI Determine whether MDR after intensification is prognostically significant VII Determine whether gene expression patterns predict disease recurrence or response to imatinib mesylate
OUTLINE This is a multicenter study This is also a dose-escalation study of imatinib mesylate in Philadelphia chromosome-positive Ph patients Patients are stratified according to Philadelphia chromosome Ph status Ph-positive vs Ph-negative or indeterminate hypodiploidy yes vs no MLL translocation 11q23 AND slow early response to prior induction therapy yes vs no and failed prior induction therapy yes vs no
Cohorts of 8-12 Ph patients receive escalating doses of imatinib mesylate according to the guidelines for each treatment block of this study until the maximum tolerated dose MTD for each treatment combination is determined The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity An additional 35 patients are treated at the MTD
CONSOLIDATION BLOCK 1 Patients receive etoposide IV over 1 hour followed by ifosfamide IV over 15 hours on days 1-5 Patients also receive methotrexate intrathecally on day 1 and filgrastim G-CSF subcutaneously SC on days 6-15 or until blood counts recover Patients with CNS 23 at diagnosis also receive intrathecal triple therapy comprising methotrexate hydrocortisone and cytarabine ITT on days 8 and 15 Ph patients in cohorts 3 4 and 5 receive oral imatinib mesylate on days 1-21 Within 4 days of starting consolidation therapy patients with biopsy-proven testicular leukemia undergo radiotherapy daily for 12 days
CONSOLIDATION BLOCK 2 Patients receive high-dose methotrexate IV over 24 hours and ITT on day 1 followed by high-dose cytarabine IV over 3 hours every 12 hours on days 2 and 3 Patients also receive leucovorin calcium IV or orally every 6 hours for 3 doses beginning on day 2 and G-CSF SC on days 4-13 or until blood counts recover Ph patients in cohorts 2 3 4 and 5 receive oral imatinib mesylate as in consolidation block 1 Patients undergoing allogeneic hematopoietic stem cell transplantation HSCT proceed to preparative chemotherapy All other patients proceed to reinduction block 1
REINDUCTION BLOCK 1 Patients receive vincristine IV on days 1 8 and 15 daunorubicin IV on days 1 and 2 cyclophosphamide IV over 30 minutes every 12 hours on days 3 and 4 pegaspargase intramuscularly IM on day 4 and ITT on days 1 and 15 Patients also receive oral dexamethasone twice daily on days 1-7 and 15-21 and G-CSF SC on days 5-14 or until blood counts recover Ph patients in cohorts 2 4 and 5 receive imatinib mesylate as in consolidation block 1
INTENSIFICATION BLOCK 1 Patients receive high-dose methotrexate IV over 24 hours on days 1 and 15 and ITT on days 1 and 22 Patients also receive leucovorin calcium IV or orally every 6 hours for 3 doses beginning on days 2 and 16 Patients receive etoposide IV over 2 hours followed by cyclophosphamide IV over 30 minutes on days 22-24 G-CSF SC on days 27-36 or until blood counts recover high-dose cytarabine IV over 3 hours every 12 hours on days 43 and 44 and asparaginase IM on day 44 Ph patients in cohorts 1 and 4 receive oral imatinib mesylate on days 43-63 and patients in cohort 5 receive oral imatinib mesylate on days 1-56
REINDUCTION BLOCK 2 Patients receive vincristine daunorubicin cyclophosphamide pegaspargase dexamethasone and G-CSF as in reinduction block 1 Patients also receive ITT on days 1 and 15 Ph patients receive imatinib mesylate as in reinduction block 1
INTENSIFICATION BLOCK 2 Patients receive methotrexate leucovorin calcium etoposide cyclophosphamide filgrastim cytarabine and asparaginase as in intensification block 1 Ph patients receive imatinib mesylate as in intensification block 1
MAINTENANCE 1 Patients receive high-dose methotrexate IV and leucovorin calcium as in consolidation block 2 Patients also receive ITT and vincristine IV on days 1 and 29 oral dexamethasone twice daily on days 1-5 and 29-33 oral methotrexate on days 8 15 and 22 oral mercaptopurine on days 8-28 etoposide IV over 2 hours followed by cyclophosphamide IV over 30 minutes on days 29-33 and G-CSF SC on days 34-43 Ph patients in cohorts 1-4 receive oral imatinib mesylate on days 29-49 and patients in cohort 5 receive oral imatinib mesylate on days 1-56 Treatment repeats every 8 weeks for 4 courses in the absence of disease progression or unacceptable toxicity
MAINTENANCE 2 Patients receive vincristine and dexamethasone as in maintenance 1 Beginning on day 1 patients undergo cranial radiotherapy once daily 5 days a week for approximately 2 weeks Patients also receive oral methotrexate on days 8 15 22 29 36 43 and 50 and oral mercaptopurine on days 11-56 Ph patients in cohorts 1-4 receive oral imatinib mesylate on days 1-21 and 29-49 and patients in cohort 5 receive oral imatinib mesylate on days 1-56
MAINTENANCE 3 Patients receive vincristine and dexamethasone as in maintenance 2 Patients also receive oral methotrexate on days 1 8 15 22 29 36 43 and 50 and oral mercaptopurine on days 1-56 Ph patients receive imatinib mesylate as in maintenance 2 Treatment repeats every 8 weeks for 7 courses 12 courses total in maintenance 1 2 and 3 in the absence of disease progression or unacceptable toxicity
Patients may undergo allogeneic HSCT after consolidation block 2 if there is an available HLA-DR matched or HLA-A or -B matched or 1 antigen mismatched relative donor
Patients with CNS leukemia undergo cranial radiotherapy 3 times daily on days -10 to -8 All patients undergo radiotherapy twice daily on days -7 to -5 and receive etoposide IV on day -4 and cyclophosphamide IV on days -3 and -2 Patients undergo allogeneic bone marrow peripheral blood stem cell or umbilical cord blood transplantation on day 0 Patients receive cyclosporine IV beginning on day -1 and continuing every 12 hours switching to oral administration when possible until day 60 and tapering thereafter Patients also receive methotrexate on days 1 3 and 6 Beginning 16-24 weeks after transplantation Ph patients receive oral imatinib mesylate once daily for 24 weeks
Patients are followed every 4-8 weeks for 1 year every 3 months for 1 year every 6 months for 1 year and then annually thereafter Patients undergoing HSCT are followed weekly for the first year
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 |
|---|---|---|---|
| U10CA098543 | NIH | CTEP | httpsreporternihgovquickSearchU10CA098543 |
| NCI-2012-01862 | REGISTRY | None | None |
| CDR0000068859 | None | None | None |
| COG-AALL0031 | None | None | None |
| AALL0031 | OTHER | None | None |
| AALL0031 | OTHER | None | None |