Erwinia Asparaginase After Allergy to PEG-Asparaginase in Treating Young Patients With Acute Lymphoblastic Leukemia
- Conditions
- Adult Acute Lymphoblastic LeukemiaChildhood Acute Lymphoblastic Leukemia
- Interventions
- 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
-
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
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)
Harbor-University of California at Los Angeles Medical Center
🇺🇸Torrance, California, United States
Kalamazoo Center for Medical Studies
🇺🇸Kalamazoo, Michigan, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Children's Hospital Central California
🇺🇸Madera, California, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Johns Hopkins All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Indiana University/Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
Lurie Children's Hospital-Chicago
🇺🇸Chicago, Illinois, United States
Rainbow Babies and Childrens Hospital
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
University of Minnesota/Masonic Cancer Center
🇺🇸Minneapolis, Minnesota, United States
UCSF Medical Center-Mount Zion
🇺🇸San Francisco, California, United States
UCSF Medical Center-Parnassus
🇺🇸San Francisco, California, United States
University of Alabama at Birmingham Cancer Center
🇺🇸Birmingham, Alabama, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Kaiser Permanente Downey Medical Center
🇺🇸Downey, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Nemours Children's Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
Advocate Christ Medical Center
🇺🇸Oak Lawn, Illinois, United States
Norton Children's Hospital
🇺🇸Louisville, Kentucky, United States
Advocate Children's Hospital-Oak Lawn
🇺🇸Oak Lawn, Illinois, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
The Childrens Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
🇺🇸New York, New York, United States
The Steven and Alexandra Cohen Children's Medical Center of New York
🇺🇸New Hyde Park, New York, United States
UNC Lineberger Comprehensive Cancer Center
🇺🇸Chapel Hill, North Carolina, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
UT Southwestern/Simmons Cancer Center-Dallas
🇺🇸Dallas, Texas, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Spectrum Health at Butterworth Campus
🇺🇸Grand Rapids, Michigan, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Saint Christopher's Hospital for Children
🇺🇸Philadelphia, Pennsylvania, United States