Phase II Trial of the Addition of PEG-Asparaginase to the Hyper-CVAD Regimen in Adult Newly-Diagnosed Acute Lymphoblastic Leukemia
- To estimate the complete response rate in patients with newly diagnosed acute
lymphoblastic leukemia treated with pegaspargase in combination with hyper-CVAD regimen
comprising cyclophosphamide, dexamethasone, vincristine sulfate, doxorubicin
hydrochloride, methotrexate, and cytarabine.
- To determine the safety and tolerability of this regimen in these patients.
- To evaluate the progression-free survival and overall survival of patients treated with
- To determine the half-life of pegaspargase when administered in combination with
- To monitor the development of neutralizing antibodies to pegaspargase when administered
in combination with hyper-CVAD regimen.
- To assess minimal residual disease by flow cytometry at the end of courses 1A and 1B.
OUTLINE: This is a multicenter study.
- Hyper-CVAD regimen (courses 1, 3, 5, and 7): Patients receive cyclophosphamide IV over
2-3 hours twice daily on days 1-3, dexamethasone IV on days 1-4 and 11-14, methotrexate
intrathecally (IT) on day 2, doxorubicin hydrochloride IV over 2 hours and pegaspargase
IV over 1-2 hours on day 4, vincristine sulfate IV on days 4 and 11, and cytarabine IT
on day 8.
- High-dose methotrexate/cytarabine regimen (courses 2, 4, 6, and 8): Patients receive
methotrexate IV continuously over 24 hours on day 1, methylprednisolone IV twice daily
on days 1-3, methotrexate IT on day 2, cytarabine IV over 2 hours twice daily on days 2
and 3, pegaspargase IV over 1-2 hours on day 3, and cytarabine IT on day 8.
Treatment repeats every 3-4 weeks for 8 courses in the absence of disease progression or
unacceptable toxicity. Patients with Philadelphia chromosome-positive disease also receive
oral imatinib mesylate daily beginning at diagnosis.
Patients who complete 8 courses of chemotherapy and are not candidates for hematopoietic
stem cell transplantation receive maintenance therapy off study.
Blood samples are collected at baseline and periodically during study for pharmacokinetics
and neutralizing antibody assays.
After completion of study therapy, patients are followed up every 6 months.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Complete response rate after course 1 of pegaspargase when administered in combination with hyper-CVAD regimen
The complete response rate after 1A cycle of a PEG-Asparaginase and hyper-CVAD combination regimen will be estimated, and an exact 95% confidence interval will be computed using a binomial distribution.
After day 4 of treatment
OHSU Knight Cancer Institute
United States: Food and Drug Administration
|OHSU Knight Cancer Institute||Portland, Oregon 97239|