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

Childhood Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00537030
• Other study ID #: AALL07P2
• Secondary ID: NCI-2009-0031607
• Status: Completed
• Phase: N/A
• Start date: February 11, 2008

Study information

• Verified date: June 2019
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 59
• Est. primary completion date: February 1, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• Adult Acute Lymphoblastic Leukemia
• Childhood Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Asparaginase
Given IM

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Pharmacological Study
Correlative studies

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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