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

Not Applicable

Completed

Conditions: Adult Acute Lymphoblastic Leukemia
Childhood Acute Lymphoblastic Leukemia

Interventions: Drug: Asparaginase
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study

Registration Number: NCT00537030

Lead Sponsor: Children's Oncology Group

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 59

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (chemotherapy)	Laboratory Biomarker Analysis	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.
Treatment (chemotherapy)	Pharmacological Study	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.
Treatment (chemotherapy)	Asparaginase	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Trough Serum Asparaginase Activity ≥ 0.1 IU/mL	48 hours post administration of Erwinia asparaginase	Percentage of participants who had trough serum asparaginase activity ≥ 0.1 IU/mL in the blood 48 hours post administration of Erwinia asparaginase

Secondary Outcome Measures

Name	Time	Method
Determine if Plasma Asparagine is Adequately Depleted	On days 12 or 13	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	At baseline, prior to doses 4, 5, and 6 and on days 15 and 22	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.
Percentage of Participants Who Experienced Toxicities	up to 1 year	The percentage of participants who experienced toxicities: Allergy rate, Hyperglycemia Rate, Pancreatitis Rate, Hemorrhage/Thrombosis Rate

Trial Locations

Locations (43): University of Alabama at Birmingham Cancer Center
🇺🇸
Birmingham, Alabama, United States
Phoenix Childrens Hospital
🇺🇸
Phoenix, Arizona, United States
Kaiser Permanente Downey Medical Center
🇺🇸
Downey, California, United States
Children's Hospital Los Angeles
🇺🇸
Los Angeles, California, United States
Children's Hospital Central California
🇺🇸
Madera, California, United States
Children's Hospital of Orange County
🇺🇸
Orange, California, United States
Rady Children's Hospital - San Diego
🇺🇸
San Diego, California, United States
UCSF Medical Center-Mount Zion
🇺🇸
San Francisco, California, United States
UCSF Medical Center-Parnassus
🇺🇸
San Francisco, California, United States
Harbor-University of California at Los Angeles Medical Center
🇺🇸
Torrance, California, United States
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University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States