Erwinia Asparaginase After Allergy to PEG-Asparaginase in Treating Young Patients With Acute Lymphoblastic Leukemia
Adult Acute Lymphoblastic Leukemia
Childhood Acute Lymphoblastic Leukemia
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pharmacology and Toxicity of Erwinia Asparaginase (Erwinase®; Crisantaspase; IND 290) Following Allergy to PEG-Asparaginase in Treatment of Children With Acute Lymphoblastic Leukemia (ALL)|
- Trough Serum Asparaginase Activity [ Time Frame: Measured in blood at 48 hours post administration of Erwinia asparaginase ] [ Designated as safety issue: No ]To determine if the 48 hour trough serum asparaginase activity is ≥ 0.1 IU/mL in at least 70% of patients.
- Determine if Plasma Asparagine is Adequately Depleted [ Time Frame: On days 12 or 13 ] [ Designated as safety issue: No ]Plasma asparagine depletion will be determined in a subset of 20 patients limited to participating Phase I Institutions.
- Presence of Anti-Erwinia Asparaginase Antibodies in Children Treated With a Course(s) of Erwinase® Following Clinical Allergy to PEG-asparaginase [ Time Frame: At baseline, prior to doses 4, 5, and 6 and on days 15 and 22 ] [ Designated as safety issue: No ]An ELISA (enzyme-linked immunosorbent assay) method will be used to determine the presence of specific anti-Erwinia and anti-PEG-asparaginase antibodies at baseline, and of specific anti-Erwinia asparaginase antibodies after first and subsequent exposures to Erwinase®. The rate of antibody formation will be described and compared informally to experience in CCG-1962 and 1961. Serum asparaginase activity will be compared during Erwinase® courses as an indication of the neutralizing effect of antibodies on the enzyme effect.
- Frequency of Asparaginase-related Toxicities Following Erwinase® Treatment. [ Time Frame: At each course of Erwinase® treatment ] [ Designated as safety issue: Yes ]As assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The incidence of these toxicities will be described. The percentage of patients that have Erwinase® therapy discontinued due to the above toxicities will also be estimated. With a sample size of 50, the incidence of the above toxicities can be estimated with a maximum standard error of 7%.
|Study Start Date:||February 2008|
|Primary Completion Date:||February 2011 (Final data collection date for primary outcome measure)|
Experimental: Erwinia asparaginase
Patients receive 6 doses of Erwinia asparaginase (dosage 25,000 IU/m2 intramuscularly (IM) on a Monday/Wednesday/Friday schedule as a replacement for each scheduled dose of PEG-asparaginase remaining on the original treatment protocol. All other chemotherapy continues according to the original treatment protocol.
Other: laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studiesDrug: asparaginase
- To determine if the 48 hour trough serum asparaginase activity is ≥0.1 IU/mL.
- To determine the frequency of asparaginase-related toxicity following Erwinase® treatment.
- To characterize the pharmacokinetics of Erwinase in children with leukemia and allergy to PEG-asparaginase.
- To informally compare serum asparaginase activity and plasma asparagine concentration between patients treated with Erwinase® on this trial and historical controls treated with PEG-asparaginase on CCG-1962 and 1961.
- To determine the 72 hour serum asparaginase activity (Day 8 (pre-dose 4) if the course of Erwinase® is started on Monday; Day 13 (pre-dose 6) if the course of Erwinase® is started on Wednesday; and Day 11 (pre-dose 5) if the course of Erwinase® is started on Friday).
- To determine the presence of anti-Erwinia asparaginase antibodies in children treated with a course(s) of Erwinase® following clinical allergy to PEG -asparaginase (PEG, pegaspargase).
- To determine if plasma asparagine is adequately depleted (Day 12 (pre-dose 6) if the course of Erwinase® is started on Monday; Day 13 (pre-dose 6) if the course of Erwinase® is started on Wednesday or Friday) in a subset of patients.
Patients receive 6 doses of Erwinia asparaginase intramuscularly (IM) on a Monday/Wednesday/Friday schedule as a replacement for each scheduled dose of PEG-asparaginase remaining on the original treatment protocol. All other chemotherapy continues according to the original treatment protocol.
Blood samples are collected periodically for pharmacokinetic, pharmacodynamic, and antibody studies.
After completion of study treatment, patients are followed periodically.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00537030
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|Principal Investigator:||Wanda Salzer, MD||Children's Oncology Group|