NCT00928200

Erwinase for Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) (IND 104224)

Intravenous Erwinase for Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia and Allergy to E. Coli Asparaginase (IND 104224)

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 1 (actual)
• Sponsor: Therapeutic Advances in Childhood Leukemia Consortium · Academic / Other
• Sex: All
• Age: 1 Year – 21 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Relapsed Acute Lymphoblastic Leukemia
• Allergy to PEG e.Coli Asparaginase
• Allergy to Native e.Coli Asparaginase

Interventions

Type	Name	Description
DRUG	Erwinase	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.
DRUG	Vincristine	1.5 mg/m2/dose IV push (maximum single dose 2 mg) on Days 1, 8, 15 and 22
DRUG	Dexamethasone	10 mg/m2/day divided BID. Give by mouth days 1-14.
DRUG	Doxorubicin	60 mg/m2/day IV over 15 minutes on day 1
DRUG	Cytarabine	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
DRUG	Methotrexate	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
DRUG	Triple Intrathecal Therapy	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.
DRUG	Dexrazoxane	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).

Timeline

• Start date: 2009-04-13
• Primary completion: 2010-06-04
• Completion: 2010-06-04
• First posted: 2009-06-25
• Last updated: 2019-02-19
• Results posted: 2019-02-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study