Erwinase for Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) (IND 104224)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00928200
Recruitment Status : Terminated (Study was terminated due to lack of accrual.)
First Posted : June 25, 2009
Last Update Posted : August 20, 2010
Information provided by:
Therapeutic Advances in Childhood Leukemia Consortium

Brief Summary:
This is a phase I study using the Erwinia form of asparaginase in place of the E. coli form using a standard re-induction regimen (Vincristine, Dexamethasone, Doxorubicin) for patients with relapsed ALL who have developed an allergy to the E. coli formulation. This study will administer the drug intravenously instead of the usual intramuscular route. The dose of Erwinia will be escalated in the absence of dose limiting toxicity. Patients must have first or second relapse ALL with a history of prior systemic reaction to E. coli asparaginase.

Condition or disease Intervention/treatment Phase
Relapsed Acute Lymphoblastic Leukemia Allergy to PEG e.Coli Asparaginase Allergy to Native e.Coli Asparaginase Drug: Erwinase Drug: Vincristine Drug: Dexamethasone Drug: Doxorubicin Drug: Cytarabine Drug: Methotrexate Drug: Triple Intrathecal Therapy Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Intravenous Erwinase for Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia and Allergy to E. Coli Asparaginase (IND 104224)
Study Start Date : May 2009
Actual Primary Completion Date : June 2010
Actual Study Completion Date : June 2010

Intervention Details:
    Drug: Erwinase
    The dose of Erwinase will be assigned at study entry. Erwinase will be administered as a 2-hour intravenous infusion. A total of 10 doses will be given on a Monday-Wednesday-Friday schedule.
    Drug: Vincristine
    1.5 mg/m2/dose IV push on days 1, 8, 15 and 22
    Drug: Dexamethasone
    10 mg/m2/day divided BID. Give by mouth days 1-14
    Drug: Doxorubicin
    60 mg/m2/day IV over 15 minutes on day 1
    Drug: Cytarabine
    Given Intrathecally at the dose defined by age on day 1. 30 mg for age 1-1.99 50 mg for age 2-2.99 70 mg for age 3 and older
    Drug: Methotrexate
    Given Intrathecally to all patients with CNS negative disease at study entry. Dose defined by age. Given on day 15 8mg for age 1-1.99 10 mg for age 2-2.99 12 mg for age 3-8.99 15 mg for age 9 and older
    Drug: Triple Intrathecal Therapy
    Methotrexate, Cytarabine and Hydrocortisone given Intrathecally on day 8, 15 and 22 for patients who are CNS positive at study entry. Doses determined by age.

Primary Outcome Measures :
  1. Maximum Tolerated Dose [ Time Frame: Each dose level is evaluated ]

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Ages Eligible for Study:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Abbreviated List of Eligibility Criteria

Inclusion Criteria:

  • Patients must have relapsed or refractory acute lymphoblastic leukemia with a M3 marrow (marrow blasts >25%) who have had no more than two prior therapeutic attempts.
  • Patients must have a history of prior systemic allergic reaction to E. coli asparaginase (native or pegylated), such as urticaria, wheezing, or anaphylaxis.
  • Patients may be in first or second relapse and should not have received more than 2 induction attempts.
  • Patients must have less than 350mg/m2 lifetime exposure of anthracycline chemotherapy.
  • Patients should not have received previous therapy using Erwinase.

Exclusion Criteria:

  • Patients with prior history of Grade 2 or greater asparaginase-induced symptomatic pancreatitis will be excluded.
  • Patients with a prior history of asparaginase associated stroke are excluded.
  • Patients will be excluded if their shortening fraction by echocardiogram is less than 30%.
  • Patients who are pregnant or nursing an infant.


  • Direct bilirubin > 1.5x the institutional upper limit of normal for age. A total bilirubin result that is less than 1.5 times the institutional upper limit of normal for age may be used for eligibility if a direct bilirubin result is not available.
  • SGPT (ALT) > 4 x institutional upper limit of normal
  • Amylase or Lipase > 2 x institutional upper limit of normal
  • Serum creatinine is > the upper limit of normal for age at the institution's laboratory.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00928200

United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States
United States, California
City of Hope
Duarte, California, United States, 91010
Miller Children's Hospital
Long Beach, California, United States
Childrens Hospital Los Angeles
Los Angeles, California, United States, 90027
Oakland Children's Hospital
Oakland, California, United States
Stanford University Medical Center
Palo Alto, California, United States, 94304-1812
UCSF School of Medicine
San Francisco, California, United States, 94143-0106
United States, Florida
University of Miami Cancer Center
Miami, Florida, United States, 33136
United States, Illinois
Children's Memorial
Chicago, Illinois, United States
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States
United States, Michigan
C.S. Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109-0914
United States, Minnesota
Childrens Hospital & Clinics of Minnesota
Minneapolis, Minnesota, United States, 55404-4597
University of Minnesota Children's Hospital
Minneapolis, Minnesota, United States
United States, New York
New York University Medical Center
New York, New York, United States, 10016
Children's Hospital New York-Presbyterian
New York, New York, United States, 10032
United States, Ohio
Nationwide Childrens Hospital
Columbus, Ohio, United States
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States
United States, Tennessee
Vanderbilt Children's Hospital
Nashville, Tennessee, United States
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Canada, Ontario
Hospital for Sick Kids
Toronto, Ontario, Canada
Sponsors and Collaborators
Therapeutic Advances in Childhood Leukemia Consortium
Study Chair: Heather Grossman, MD Children's Hopital New York
Principal Investigator: Paul Gaynon, md Therapeutic Advances in Childhood Leukemia

Additional Information:
Responsible Party: Heather Grossman, Therapeutic Advances in Childhood Leukemia Consortium Identifier: NCT00928200     History of Changes
Other Study ID Numbers: T2006-002
First Posted: June 25, 2009    Key Record Dates
Last Update Posted: August 20, 2010
Last Verified: August 2010

Keywords provided by Therapeutic Advances in Childhood Leukemia Consortium:

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors