Clinical trial NCT00928200
Conditions: Relapsed Acute Lymphoblastic Leukemia Allergy to PEG e.Coli Asparaginase Allergy to Native e.Coli Asparaginase
Keywords: Relapsed Allergy Erwinia Acute Lymphoblastic Leukemia
Sponsor: Therapeutic Advances in Childhood Leukemia Consortium
Start date: 2009-04-13; Completion date: 2010-06-04
Enrollment: 1 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a phase I study using the Erwinia form of asparaginase in place of the E. coli form using a standard re-induction regimen (Vincristine, Dexamethasone, Doxorubicin) for patients with relapsed ALL who have developed an allergy to the E. coli formulation. This study will administer the drug intravenously instead of the usual intramuscular route. The dose of Erwinia will be escalated in the absence of dose limiting toxicity. Patients must have first or second relapse ALL with a history of prior systemic reaction to E. coli asparaginase.

Detailed description:
Significance

1. Substitution of Erwinase after E.coli asparaginase allergy has been standard practice despite the paucity of evidence regarding its efficacy and uncertainty about dose. Definition of an appropriate dose and schedule of Erwinase that provides reliable asparagine depletion may be useful for patients with clinical allergy to E. coli asparaginase, both in first remission or after relapse.
2. Patients in relapse may have a different level of asparagine synthesis than patients maintaining remission and require different asparaginase dosing.5
3. Intravenous administration provides more rapid and predictable asparagine depletion with less discomfort and danger of bleeding for often thrombocytopenic patients than intramuscular administration.
4. Vincristine, doxorubicin, asparaginase, and dexamethasone with dexrazoxane is clinically relevant for a population with first marrow relapse.
5. Vincristine, doxorubicin, asparaginase, and dexamethasone with dexrazoxane is clinically relevant for a population with second marrow relapse, if the duration of CR2 \> 18 months year.

Arms: arm 1: All patients receive Vincristine, Dexamethasone, Doxorubicin, and Cytarabine. Dexrazoxane optional on Day 1. Erwinase is started between Days 3-5 and is given every M-W-F for a total of 10 doses. Patients with CNS 1 or 2 receive Methotrexate intrathecally on Day 15. Patients with CNS 3 receive Triple Intrathecal Therapy (Methotrexate, Cytarabine and Hydrocortisone) on Days 8, 15, and 22.
Interventions: intervention 1: Erwinase intervention 2: Vincristine intervention 3: Dexamethasone intervention 4: Doxorubicin intervention 5: Cytarabine intervention 6: Methotrexate intervention 7: Triple Intrathecal Therapy intervention 8: Dexrazoxane
Intervention descriptions: intervention 1: The dose of Erwinase will be assigned at study entry. The first dose of Erwinase wil be given between Days 3-5 and will continue on a M-W-F schedule for a total of 10 doses.

Erwinase will be administered as a 2-hour intravenous infusion. intervention 2: 1.5 mg/m2/dose IV push (maximum single dose 2 mg) on Days 1, 8, 15 and 22 intervention 3: 10 mg/m2/day divided BID. Give by mouth days 1-14. intervention 4: 60 mg/m2/day IV over 15 minutes on day 1 intervention 5: Given Intrathecally at the dose defined by age on day 1. 30 mg for age 1-1.99 50 mg for age 2-2.99 70 mg for age 3 and older intervention 6: Given Intrathecally to all patients who are CNS 1 or 2 at study entry. Dose defined by age. Given on day 15 8mg for age 1-1.99 10 mg for age 2-2.99 12 mg for age 3-8.99 15 mg for age 9 and older intervention 7: Methotrexate, Cytarabine and Hydrocortisone given Intrathecally on day 8, 15 and 22 for patients who are CNS 3 at study entry. Doses determined by age. intervention 8: Due to the limited availability of Dexrazoxane (Zinecard®), treatment will be at the discretion of the treating physician. Dose should be 600 mg/m2 as a IV push immediately prior to anthracycline dose (the elapsed time from the beginning of the dexrazoxane dose to the end of the anthracycline infusion should be 30 minutes or less).

Protocol documents: