Ignite Creation Date:
2024-05-05 @ 11:27 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00049569
Status:
COMPLETED
Last Update Posted:
2013-10-08
First Post:
2002-11-12
Brief Title:
Combination Chemotherapy and Imatinib Mesylate in Treating Children With Relapsed Acute Lymphoblastic Leukemia
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
Intensive Induction Therapy for Children With Acute Lymphoblastic Leukemia ALL Who Experience a Bone Marrow Relapse
Status:
COMPLETED
Status Verified Date:
2013-10
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:
Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth Combining more than one chemotherapy drug with imatinib mesylate may kill more cancer cells Randomized phase II trial to study the effectiveness of combination chemotherapy and imatinib mesylate in treating children who have relapsed acute lymphoblastic leukemia
Detailed Description:
PRIMARY OBJECTIVES
I To assess the feasibility and safety of using an intensified sequential induction regimen to treat children with acute lymphoblastic leukemia ALL who experience an isolated or combined bone marrow relapse
II To determine the potential of this regimen to serve as a backbone for the future testing of novel therapeutic agents
SECONDARY OBJECTIVES
I To estimate the remission re-induction rates and four-month event-free survival EFS for children stratified by the duration of first remission
II To determine the feasibility of measuring minimal residual disease MRD quantitatively in all patients at time points throughout re-induction and to correlate post-remission events with disease burden during induction
III To use deoxyribonucleic acid DNA arrays to characterize patterns of gene expression that predict treatment failure and to compare gene expression profiles at the time of relapse with those at the time of initial diagnosis to gain an understanding of the pathways that may be involved in disease recurrence
IV To determine the feasibility of combining intensive re-induction therapy with imatinib mesylate STI571 for children with a relapse of Philadelphia chromosome positive Ph ALL
OUTLINE Patients are randomized to 1 of 2 treatment arms
ARM I
Treatment Block 1 Patients receive cytarabine intrathecally IT on day 1 and methotrexate IT on days 15 and 29 Patients also receive vincristine intravenously IV on days 1 8 15 and 22 prednisone orally PO twice or thrice daily BID or TID on days 1-29 pegaspargase intramuscularly IM on days 2 8 15 and 22 and doxorubicin IV over 15 minutes on day 1 Ph-positive patients also receive imatinib mesylate PO on days 1-14
Treatment Block 2 Patients receive methotrexate IT on days 1 and 22 cyclophosphamide IV over 30 minutes and etoposide IV over 2 hours on days 1-5 and filgrastim G-CSF subcutaneously SC beginning on day 6 and continuing until blood counts recover Patients also receive methotrexate IV over 24 hours on day 22 followed by leucovorin calcium IV every 6 hours on days 24 and 25 Ph-positive patients receive imatinib mesylate PO on days 1-14
Treatment Block 3a Ph-negative patients Patients receive cytarabine IV over 3 hours every 12 hours on days 1 2 8 and 9 asparaginase IM on days 2 and 9 and G-CSF SC beginning on day 10 and continuing until blood counts recover
Treatment Block 3b Ph-positive patients Patients receive cytarabine IV over 3 hours every 12 hours on days 1 and 2 asparaginase IM on day 2 and G-CSF SC beginning on day 3 and continuing until blood counts recover Patients also receive imatinib mesylate PO on days 1-14
ARM II
Treatment Block 1 Patients receive cytarabine IT on day 1 and then methotrexate cytarabine and hydrocortisone IT triple intrathecal therapy TIT on days 8 15 22 and 29 Vincristine prednisone pegaspargase doxorubicin and imatinib mesylate are administered as in arm I
Treatment Block 3 Patients receive cytarabine asparaginase G-CSF and imatinib mesylate as in arm I
Treatment Block 2 Patients receive TIT on days 1 and 22 Patients then receive cyclophosphamide etoposide G-CSF methotrexate IV leucovorin calcium and imatinib mesylate as in arm I After each block is completed disease is assessed The next block is started on day 36 if blood counts have recovered and marrow during block 1 is at least M2M3 Patients are removed from protocol therapy if disease progresses unacceptable toxicity occurs marrow is M2M3 at day 15 of the second administered block of treatment or cerebrospinal fluid blasts persist after 6 weekly doses of TIT
After completion of study treatment patients are followed up for 4 months
PROJECTED ACCRUAL A total of 63-126 patients will be accrued for this study within 14 months
I To assess the feasibility and safety of using an intensified sequential induction regimen to treat children with acute lymphoblastic leukemia ALL who experience an isolated or combined bone marrow relapse
II To determine the potential of this regimen to serve as a backbone for the future testing of novel therapeutic agents
SECONDARY OBJECTIVES
I To estimate the remission re-induction rates and four-month event-free survival EFS for children stratified by the duration of first remission
II To determine the feasibility of measuring minimal residual disease MRD quantitatively in all patients at time points throughout re-induction and to correlate post-remission events with disease burden during induction
III To use deoxyribonucleic acid DNA arrays to characterize patterns of gene expression that predict treatment failure and to compare gene expression profiles at the time of relapse with those at the time of initial diagnosis to gain an understanding of the pathways that may be involved in disease recurrence
IV To determine the feasibility of combining intensive re-induction therapy with imatinib mesylate STI571 for children with a relapse of Philadelphia chromosome positive Ph ALL
OUTLINE Patients are randomized to 1 of 2 treatment arms
ARM I
Treatment Block 1 Patients receive cytarabine intrathecally IT on day 1 and methotrexate IT on days 15 and 29 Patients also receive vincristine intravenously IV on days 1 8 15 and 22 prednisone orally PO twice or thrice daily BID or TID on days 1-29 pegaspargase intramuscularly IM on days 2 8 15 and 22 and doxorubicin IV over 15 minutes on day 1 Ph-positive patients also receive imatinib mesylate PO on days 1-14
Treatment Block 2 Patients receive methotrexate IT on days 1 and 22 cyclophosphamide IV over 30 minutes and etoposide IV over 2 hours on days 1-5 and filgrastim G-CSF subcutaneously SC beginning on day 6 and continuing until blood counts recover Patients also receive methotrexate IV over 24 hours on day 22 followed by leucovorin calcium IV every 6 hours on days 24 and 25 Ph-positive patients receive imatinib mesylate PO on days 1-14
Treatment Block 3a Ph-negative patients Patients receive cytarabine IV over 3 hours every 12 hours on days 1 2 8 and 9 asparaginase IM on days 2 and 9 and G-CSF SC beginning on day 10 and continuing until blood counts recover
Treatment Block 3b Ph-positive patients Patients receive cytarabine IV over 3 hours every 12 hours on days 1 and 2 asparaginase IM on day 2 and G-CSF SC beginning on day 3 and continuing until blood counts recover Patients also receive imatinib mesylate PO on days 1-14
ARM II
Treatment Block 1 Patients receive cytarabine IT on day 1 and then methotrexate cytarabine and hydrocortisone IT triple intrathecal therapy TIT on days 8 15 22 and 29 Vincristine prednisone pegaspargase doxorubicin and imatinib mesylate are administered as in arm I
Treatment Block 3 Patients receive cytarabine asparaginase G-CSF and imatinib mesylate as in arm I
Treatment Block 2 Patients receive TIT on days 1 and 22 Patients then receive cyclophosphamide etoposide G-CSF methotrexate IV leucovorin calcium and imatinib mesylate as in arm I After each block is completed disease is assessed The next block is started on day 36 if blood counts have recovered and marrow during block 1 is at least M2M3 Patients are removed from protocol therapy if disease progresses unacceptable toxicity occurs marrow is M2M3 at day 15 of the second administered block of treatment or cerebrospinal fluid blasts persist after 6 weekly doses of TIT
After completion of study treatment patients are followed up for 4 months
PROJECTED ACCRUAL A total of 63-126 patients will be accrued for this study within 14 months
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-2012-01798 | REGISTRY | None | None |
| COG-AALL01P2 | None | None | None |
| CDR0000258120 | None | None | None |
| AALL01P2 | OTHER | None | None |
| AALL01P2 | OTHER | None | None |
| U10CA098543 | NIH | CTEP | httpsreporternihgovquickSearchU10CA098543 |