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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

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment (chemotherapy)Laboratory Biomarker AnalysisPatients 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 StudyPatients 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)AsparaginasePatients 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
NameTimeMethod
Percentage of Participants With Trough Serum Asparaginase Activity ≥ 0.1 IU/mL48 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
NameTimeMethod
Determine if Plasma Asparagine is Adequately DepletedOn 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-asparaginaseAt 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 Toxicitiesup 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

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