Erwinia Asparaginase After Allergy to PEG-Asparaginase in Treating Young Patients With Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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This clinical trial is studying the side effects of Erwinia asparaginase and what happens to the drug in the body in treating young patients with acute lymphoblastic leukemia who are allergic to PEG-asparaginase. Drugs used in chemotherapy, such as Erwinia asparaginase, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine if the 48-hour trough serum asparaginase activity is ? 0.1 IU/mL in young patients with acute lymphoblastic leukemia treated with Erwinia asparaginase after allergy to PEG-asparaginase. II. To determine the frequency of asparaginase-related toxicity in these patients. III. To characterize the pharmacokinetics of Erwinia asparaginase in these patients. SECONDARY OBJECTIVES: I. To compare serum asparaginase activity and serum asparagine concentration between patients treated with Erwinia asparaginase on this trial and historical controls treated with PEG-asparaginase on CCG-1961 and CCG-1962. II. To determine the 72-hour serum asparaginase activity on days 8 or 11 or 13 based on the starting date of Erwinia asparaginase therapy. III. To determine the presence of anti-Erwinia asparaginase antibodies in patients treated with a course(s) of Erwinia asparaginase following clinical allergy to PEG-asparaginase (PEG, pegaspargase). IV. To determine if serum asparagine is adequately depleted on days 12 or 13 in a subset of these patients. OUTLINE: This is a multicenter study. 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.

Official Title
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Pharmacology and Toxicity of Erwinia Asparaginase (Erwinase?; Crisantaspase; IND 290) Following Allergy to PEG-Asparaginase in Treatment of Children With Acute Lymphoblastic Leukemia (ALL)

Conditions
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Adult Acute Lymphoblastic Leukemia, Childhood Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: Asparaginase
* Other: Laboratory Biomarker Analysis
* Other: Pharmacological Study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of acute lymphoblastic leukemia Concurrently enrolled on a frontline Children's Oncology Group treatment trial (i.e., COG-AALL0232 or COG-AALL0531, COG-AALL0331, or COG-AALL0434) at a participating institution Must have 1 or more courses of asparaginase remaining to be administered on the treatment protocol Must have had a grade ? 2 hypersensitivity reaction to PEG-asparaginase No history of pancreatitis ? grade 2 No prior Erwinia asparaginase

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (chemotherapy)<br>Patients receive 6 doses of Erwinia asparaginase 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. | Drug: Asparaginase<br>* Given IM<br>* Other names: Spectrila;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Pharmacological Study<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Trough Serum Asparaginase Activity ≥ 0.1 IU/mL | Percentage of participants who had trough serum asparaginase activity ≥ 0.1 IU/mL in the blood 48 hours post administration of Erwinia asparaginase | 48 hours post administration of Erwinia asparaginase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine if Plasma Asparagine is Adequately Depleted | Plasma asparagine depletion will be determined in a subset of 20 patients limited to participating Phase I Institutions. | On days 12 or 13 | 
| Presence of Anti-Erwinia Asparaginase Antibodies in Children Treated With a Course(s) of Erwinase® Following Clinical Allergy to PEG-asparaginase | 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. | At baseline, prior to doses 4, 5, and 6 and on days 15 and 22 | 
| Percentage of Participants Who Experienced Toxicities | The percentage of participants who experienced toxicities: Allergy rate, Hyperglycemia Rate, Pancreatitis Rate, Hemorrhage/Thrombosis Rate | up to 1 year |