Erwinase for Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) (IND 104224)
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|ClinicalTrials.gov Identifier: NCT00928200|
Recruitment Status : Terminated (Study was terminated due to lack of accrual.)
First Posted : June 25, 2009
Results First Posted : February 19, 2019
Last Update Posted : February 19, 2019
|Condition or disease||Intervention/treatment||Phase|
|Relapsed Acute Lymphoblastic Leukemia Allergy to PEG e.Coli Asparaginase Allergy to Native e.Coli Asparaginase||Drug: Erwinase Drug: Vincristine Drug: Dexamethasone Drug: Doxorubicin Drug: Cytarabine Drug: Methotrexate Drug: Triple Intrathecal Therapy Drug: Dexrazoxane||Phase 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.
- Patients in relapse may have a different level of asparagine synthesis than patients maintaining remission and require different asparaginase dosing.5
- Intravenous administration provides more rapid and predictable asparagine depletion with less discomfort and danger of bleeding for often thrombocytopenic patients than intramuscular administration.
- Vincristine, doxorubicin, asparaginase, and dexamethasone with dexrazoxane is clinically relevant for a population with first marrow relapse.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Intravenous Erwinase for Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia and Allergy to E. Coli Asparaginase (IND 104224)|
|Study Start Date :||April 13, 2009|
|Actual Primary Completion Date :||June 4, 2010|
|Actual Study Completion Date :||June 4, 2010|
Experimental: Single Arm
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.
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.
1.5 mg/m2/dose IV push (maximum single dose 2 mg) on Days 1, 8, 15 and 22
10 mg/m2/day divided BID. Give by mouth days 1-14.
60 mg/m2/day IV over 15 minutes on day 1
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
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.
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).
Other Name: Zinecard
- Occurrence of a Dose-Limiting Toxicity [ Time Frame: Beginning with the first dose of investigational product until 30 days following the last dose of Erwinase ]The MTD in each stratum will be the highest dose at which 1 or fewer of six patients experience DLT during cycle 1 of therapy.
- Response Rate and Minimum Residual Disease [ Time Frame: After completion of treatment course ]Disease response evaluated by examination and labs. MRD evaluated from marrow samples.
- Asparaginase Activity [ Time Frame: PK samples to be collected Pre-Tx, and and Erwinase Doses 3, 6 and 9 and Day 29 ]Activity levels assessed from PK sampling
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00928200
|United States, California|
|Childrens Hospital Los Angeles|
|Los Angeles, California, United States, 90027|
|Study Chair:||Heather Grossman, MD||Children's Hopital New York|
|Principal Investigator:||Paul Gaynon, MD||Children's Hospital Los Angeles|