Erwinase for Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) (IND 104224) - Full Text View

Purpose

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	Intervention	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
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: 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)

Resource links provided by NLM:

MedlinePlus related topics: Allergy Chronic Lymphocytic Leukemia Leukemia

Drug Information available for: Dexamethasone Methotrexate Cytarabine Dexamethasone acetate Vincristine sulfate Dexamethasone sodium phosphate Asparaginase Methotrexate sodium Doxorubicin Doxorubicin hydrochloride

U.S. FDA Resources

Further study details as provided by Therapeutic Advances in Childhood Leukemia Consortium:

Primary Outcome Measures:

Maximum Tolerated Dose [ Time Frame: Each dose level is evaluated ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	30
Study Start Date:	May 2009
Study Completion Date:	June 2010
Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Intervention Details:

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.

1.5 mg/m2/dose IV push on days 1, 8, 15 and 22

10 mg/m2/day divided BID. Give by mouth days 1-14

60 mg/m2/day IV over 15 minutes on day 1

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

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

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.

Eligibility

Ages Eligible for Study:	1 Year to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

LABS

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00928200

Locations

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
Children's Hospital New York-Presbyterian
New York, New York, United States, 10032
New York University Medical Center
New York, New York, United States, 10016
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

Investigators

Study Chair:	Heather Grossman, MD	Children's Hopital New York
Principal Investigator:	Paul Gaynon, md	Therapeutic Advances in Childhood Leukemia

More Information

Additional Information:

For more information about this and other clinical trials, please visit the TACL website. This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Heather Grossman, Therapeutic Advances in Childhood Leukemia Consortium
ClinicalTrials.gov Identifier:	NCT00928200 History of Changes
Other Study ID Numbers:	T2006-002
Study First Received:	June 24, 2009
Last Updated:	August 18, 2010
Health Authority:	United States: Food and Drug Administration Canada: Health Canada Brazil: National Committee of Ethics in Research Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Therapeutic Advances in Childhood Leukemia Consortium:

Relapsed
Allergy
Erwinia

Acute
Lymphoblastic
Leukemia

Additional relevant MeSH terms:

Hypersensitivity
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Asparaginase
Cytarabine
Dexamethasone
Doxorubicin
Methotrexate

Vincristine
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 23, 2013