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

June 25, 2019 updated by: Children's Oncology Group

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

59

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham Cancer Center
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Phoenix Childrens Hospital
    • California
      • Downey, California, United States, 90242
        • Kaiser Permanente Downey Medical Center
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles
      • Madera, California, United States, 93636-8762
        • Children's Hospital Central California
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County
      • San Diego, California, United States, 92123
        • Rady Children's Hospital - San Diego
      • San Francisco, California, United States, 94115
        • UCSF Medical Center-Mount Zion
      • San Francisco, California, United States, 94143
        • UCSF Medical Center-Parnassus
      • Torrance, California, United States, 90502
        • Harbor-University of California at Los Angeles Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Medical Center
    • Florida
      • Jacksonville, Florida, United States, 32207
        • Nemours Children's Clinic-Jacksonville
      • Saint Petersburg, Florida, United States, 33701
        • Johns Hopkins All Children's Hospital
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Lurie Children's Hospital-Chicago
      • Oak Lawn, Illinois, United States, 60453
        • Advocate Children's Hospital-Oak Lawn
      • Oak Lawn, Illinois, United States, 60453-2699
        • Advocate Christ Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University/Melvin and Bren Simon Cancer Center
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Norton Children's Hospital
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
        • Spectrum Health at Butterworth Campus
      • Kalamazoo, Michigan, United States, 49008
        • Kalamazoo Center for Medical Studies
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Children's Hospitals and Clinics of Minnesota - Minneapolis
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota/Masonic Cancer Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • The Childrens Mercy Hospital
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New York
      • New Hyde Park, New York, United States, 11040
        • The Steven and Alexandra Cohen Children's Medical Center of New York
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • UNC Lineberger Comprehensive Cancer Center
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Cleveland, Ohio, United States, 44106
        • Rainbow Babies and Childrens Hospital
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19134
        • Saint Christopher's Hospital for Children
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of UPMC
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University/Ingram Cancer Center
    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern/Simmons Cancer Center-Dallas
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center
    • Utah
      • Salt Lake City, Utah, United States, 84113
        • Primary Children's Hospital
    • Washington
      • Seattle, Washington, United States, 98105
        • Seattle Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 months to 28 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (chemotherapy)
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.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies
Drug: Asparaginase
Given IM
Other Names:
  • Elspar
  • ASP-1
  • Asparaginase II
  • Asparaginase-E.Coli
  • Colaspase
  • Kidrolase
  • L-Asnase
  • L-ASP
  • L-Asparaginase
  • Laspar
  • Lcf-ASP
  • Leucogen
  • Leunase
  • MK-965
  • Paronal
  • Re-82-TAD-15
  • Serasa
  • Spectrila
  • L-Asparagine amidohydrolase

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Trough Serum Asparaginase Activity ≥ 0.1 IU/mL
Time Frame: 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
48 hours post administration of Erwinia asparaginase

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Wanda Salzer, Children's Oncology Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 11, 2008

Primary Completion (Actual)

February 1, 2011

Study Registration Dates

First Submitted

September 27, 2007

First Submitted That Met QC Criteria

September 27, 2007

First Posted (Estimate)

September 28, 2007

Study Record Updates

Last Update Posted (Actual)

July 9, 2019

Last Update Submitted That Met QC Criteria

June 25, 2019

Last Verified

June 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AALL07P2 (Other Identifier: CTEP)
  • U10CA098543 (U.S. NIH Grant/Contract)
  • 07-162
  • NCI-2009-00316 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • COG-AALL07P2
  • CDR0000566349

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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