A Study of Children With Refractory or Relapsed Acute Lymphoblastic Leukemia (ALLR16)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- To compare in a randomized trial the depletion of asparagine in patients who receive the native form of asparaginase or PEG-asparaginase during induction therapy.
Study Overview
Brief Summary
The main purpose of this study is to find out which form of asparaginase (the native E. coli/Erwinia) 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 I/II 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 2.4 mg/m2 ; IV over 30 min in 5 doses Days 1-5
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- — to 18 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
1
Native asparaginase
Intervention: Topotecan, dexamethasone, vincristine (Drug)
1
Native asparaginase
Intervention: E. coli Asparaginase, PEG-L-asparaginase (Drug)
1
Native asparaginase
Intervention: erwinia asparaginase (Drug)
1
Native asparaginase
Intervention: fludarabine, methotrexate, mercaptopurine (Drug)
1
Native asparaginase
Intervention: idarubicin, etoposide, cytarbine, teniposide (Drug)
1
Native asparaginase
Intervention: chemotherapy, intrathecal chemotherapy, steroid therapy (Procedure)
2
PEG-asparaginase
Intervention: Topotecan, dexamethasone, vincristine (Drug)
2
PEG-asparaginase
Intervention: E. coli Asparaginase, PEG-L-asparaginase (Drug)
2
PEG-asparaginase
Intervention: erwinia asparaginase (Drug)
2
PEG-asparaginase
Intervention: fludarabine, methotrexate, mercaptopurine (Drug)
2
PEG-asparaginase
Intervention: idarubicin, etoposide, cytarbine, teniposide (Drug)
2
PEG-asparaginase
Intervention: chemotherapy, intrathecal chemotherapy, steroid therapy (Procedure)
Outcomes
Primary Outcomes
To compare in a randomized trial the depletion of asparagine in patients who receive the native form of asparaginase or PEG-asparaginase during induction therapy.
Time Frame: December 2003
Secondary Outcomes
No secondary outcomes reported