Ignite Creation Date:
2024-05-05 @ 11:56 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00187083
Status:
COMPLETED
Last Update Posted:
2008-06-04
First Post:
2005-09-12
Brief Title:
A Study of Children With Refractory or Relapsed ALL
Sponsor:
St Jude Childrens Research Hospital
Organization:
St Jude Childrens Research Hospital
Study Overview
Official Title:
A Study of Children With Refractory or Relapsed Acute Lymphoblastic Leukemia ALLR16
Status:
COMPLETED
Status Verified Date:
2008-06
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:
The main purpose of this study is to find out which form of asparaginase the native E coliErwinia or PEG-asparaginase is more effective during induction treatment for children with acute lymphoblastic leukemia that has come back after treatment relapsed or is resistant to treatment refractory
Detailed Description:
The present protocol will compare the biologic effects of PEG-asparaginase vs native-forms of asparaginase in a randomized trial using the same dosages and schedules used in the POG 9411 study Comprehensive studies including the measurement of antibodies and asparagine levels as well as the pharmacokinetics of L-asparaginase will be performed This protocol will also study the changes in topoisomerase I and topoisomerase II levels and the fractions of topoisomerase III translocations in malignant lymphoblasts after upfront window topotecan therapy and correlate oncolytic response with these changes
Secondary objectives include
To compare changes in asparagine levels 28 days after initiation of treatment with asparaginase between the two groups
To estimate the pharmacokinetics of L-asparaginase compare the pharmacokinetics between the two groups of patients and correlate the pharmacokinetics with the development of antibody to asparaginase and depletion of asparagine
To measure the pharmacokinetics and pharmacodynamics of topotecan in patients with recurrent acute lymphoblastic leukemia
To determine whether the frequency of recombinogenesis in lymphocytes is increased during or after etoposide therapy relative to the pre-therapy level and to explore whether etoposide pharmacokinetics are related to the Day 7 or post-therapy level of recombinogenesis
Detailed Description of Treatment Plan
WINDOW Topotecan 24 mgm2 IV over 30 min in 5 doses Days 1-5
STANDARD INDUCTION Dexamethasone 6 mgm2day orally Days 8-35 Vincristine 15 mgm2 max 20 mg days 8 15 22 29
RANDOMIZE E coli asparaginase 10000 Um2day IM or Erwinia if previous allergy to E coli Days 8 11 13 15 18 20 22 25 27 29 32 34
OR
PEG-Asparaginase 2500 Um2day IM Days 8 15 22 29
ITHMA Days 8 22 36
CONSOLIDATION
Fludarabine 15 mgm2 IV over 30 min days 1234 Ara-C 2 gm2 IV days 1234
Patients who achieve remission on R16 induction or consolidation may be eligible for either a matched sibling or a fully matchedone-antigen-mismatched unrelated donor transplant
For patients not undergoing bone marrow transplant
SECONDARY CONSOLIDATION
VP 16 50 mgm2 PO qd for 14 days Vincristine 15 mgm2 max 20 mg IV days 1 8 IT MHA day 1
CONTINUATION CHEMOTHERAPY
Cycle 1
Cyclophosphamide 1 gm2 IV on days 1 and 2 Vincristine 15 mgm2 IV on day 1 max 20 mg
Cycle 2
VP-16 50 mgm2 day PO daily x 14 days Decadron 6 mgm2 PO daily TID x 14 days Vincristine 15 mgm2 IV max 2 mg on days 1 and 8
Cycle 3
HD MTX 5 gmm2 continuous infusion over 24 hrs E coli Asparaginase 10000 Um2dose IM qod x3 or PEG Asparaginase 2500 Um2dose IM x 1 maintain same randomization for Asparaginase preparation as during induction
Cycle 4
High Dose Ara-C 2 gm2dose IV over 2 hrs q 12 hrs x 3 dosesTotal dose 6 gmm2 Idarubicin 12 mgm2 IV over 30 min X 1 after completion of first dose of Ara-C IT MHA on day 1 prior to the HDARA-C dose of ITMHA is age adjusted as outlined in section 73
STANDARD CONTINUATION CHEMOTHERAPY
Patients will receive 4-week rotational cycles of chemotherapy with the following pairs of drugs for total treatment duration of 17 months
Week 1 Cyclophosphamide 300 mgm2 IV VCR 15 mgm2 IV max 2 mg Week 2 VM26 200 mgm2 IV Ara C 300 mgm2 IV Week 3 MTX MTX should be given IM or as a 2 hr IV infusion if the patient has had previous cranial iradiation 40 mgm2 IVIM 6 MP 75 mgm2 PO q HS x 7 Week 4 MTX MTX should be given IM or as a 2 hr IV infusion if the patient has had previous cranial irradiation40 mgm2 IVIM 6 MP 75 mgm2 PO q HS x 7
IT MHA Given every 8 weeks throughout standard continuation chemotherapy for patients with CNS 1 status Given every 4 weeks for patients with CNS 23 status who will receive CSI at the end of chemotherapy
Secondary objectives include
To compare changes in asparagine levels 28 days after initiation of treatment with asparaginase between the two groups
To estimate the pharmacokinetics of L-asparaginase compare the pharmacokinetics between the two groups of patients and correlate the pharmacokinetics with the development of antibody to asparaginase and depletion of asparagine
To measure the pharmacokinetics and pharmacodynamics of topotecan in patients with recurrent acute lymphoblastic leukemia
To determine whether the frequency of recombinogenesis in lymphocytes is increased during or after etoposide therapy relative to the pre-therapy level and to explore whether etoposide pharmacokinetics are related to the Day 7 or post-therapy level of recombinogenesis
Detailed Description of Treatment Plan
WINDOW Topotecan 24 mgm2 IV over 30 min in 5 doses Days 1-5
STANDARD INDUCTION Dexamethasone 6 mgm2day orally Days 8-35 Vincristine 15 mgm2 max 20 mg days 8 15 22 29
RANDOMIZE E coli asparaginase 10000 Um2day IM or Erwinia if previous allergy to E coli Days 8 11 13 15 18 20 22 25 27 29 32 34
OR
PEG-Asparaginase 2500 Um2day IM Days 8 15 22 29
ITHMA Days 8 22 36
CONSOLIDATION
Fludarabine 15 mgm2 IV over 30 min days 1234 Ara-C 2 gm2 IV days 1234
Patients who achieve remission on R16 induction or consolidation may be eligible for either a matched sibling or a fully matchedone-antigen-mismatched unrelated donor transplant
For patients not undergoing bone marrow transplant
SECONDARY CONSOLIDATION
VP 16 50 mgm2 PO qd for 14 days Vincristine 15 mgm2 max 20 mg IV days 1 8 IT MHA day 1
CONTINUATION CHEMOTHERAPY
Cycle 1
Cyclophosphamide 1 gm2 IV on days 1 and 2 Vincristine 15 mgm2 IV on day 1 max 20 mg
Cycle 2
VP-16 50 mgm2 day PO daily x 14 days Decadron 6 mgm2 PO daily TID x 14 days Vincristine 15 mgm2 IV max 2 mg on days 1 and 8
Cycle 3
HD MTX 5 gmm2 continuous infusion over 24 hrs E coli Asparaginase 10000 Um2dose IM qod x3 or PEG Asparaginase 2500 Um2dose IM x 1 maintain same randomization for Asparaginase preparation as during induction
Cycle 4
High Dose Ara-C 2 gm2dose IV over 2 hrs q 12 hrs x 3 dosesTotal dose 6 gmm2 Idarubicin 12 mgm2 IV over 30 min X 1 after completion of first dose of Ara-C IT MHA on day 1 prior to the HDARA-C dose of ITMHA is age adjusted as outlined in section 73
STANDARD CONTINUATION CHEMOTHERAPY
Patients will receive 4-week rotational cycles of chemotherapy with the following pairs of drugs for total treatment duration of 17 months
Week 1 Cyclophosphamide 300 mgm2 IV VCR 15 mgm2 IV max 2 mg Week 2 VM26 200 mgm2 IV Ara C 300 mgm2 IV Week 3 MTX MTX should be given IM or as a 2 hr IV infusion if the patient has had previous cranial iradiation 40 mgm2 IVIM 6 MP 75 mgm2 PO q HS x 7 Week 4 MTX MTX should be given IM or as a 2 hr IV infusion if the patient has had previous cranial irradiation40 mgm2 IVIM 6 MP 75 mgm2 PO q HS x 7
IT MHA Given every 8 weeks throughout standard continuation chemotherapy for patients with CNS 1 status Given every 4 weeks for patients with CNS 23 status who will receive CSI at the end of chemotherapy
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