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

Overview[ - collapse ][ - ]

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.
ConditionRelapsed Acute Lymphoblastic Leukemia
Allergy to PEG e.Coli Asparaginase
Allergy to Native e.Coli Asparaginase
InterventionDrug: Erwinase
Drug: Vincristine
Drug: Dexamethasone
Drug: Doxorubicin
Drug: Cytarabine
Drug: Methotrexate
Drug: Triple Intrathecal Therapy
PhasePhase 1
SponsorTherapeutic Advances in Childhood Leukemia Consortium
Responsible PartyTherapeutic Advances in Childhood Leukemia Consortium
ClinicalTrials.gov IdentifierNCT00928200
First ReceivedJune 24, 2009
Last UpdatedAugust 18, 2010
Last verifiedAugust 2010

Tracking Information[ + expand ][ + ]

First Received DateJune 24, 2009
Last Updated DateAugust 18, 2010
Start DateMay 2009
Estimated Primary Completion DateJune 2010
Current Primary Outcome MeasuresMaximum Tolerated Dose [Time Frame: Each dose level is evaluated] [Designated as safety issue: Yes]
Current Secondary Outcome MeasuresNot Provided

Descriptive Information[ + expand ][ + ]

Brief TitleErwinase for Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) (IND 104224)
Official TitleIntravenous Erwinase for Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia and Allergy to E. Coli Asparaginase (IND 104224)
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.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 1
Study DesignAllocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition
  • Relapsed Acute Lymphoblastic Leukemia
  • Allergy to PEG e.Coli Asparaginase
  • Allergy to Native e.Coli Asparaginase
InterventionDrug: 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.
Study Arm (s)Not Provided

Recruitment Information[ + expand ][ + ]

Recruitment StatusTerminated
Estimated Enrollment30
Estimated Completion DateJune 2010
Estimated Primary Completion DateJune 2010
Eligibility 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.
GenderBoth
Ages1 Year
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States, Canada

Administrative Information[ + expand ][ + ]

NCT Number NCT00928200
Other Study ID NumbersT2006-002
Has Data Monitoring CommitteeYes
Information Provided ByTherapeutic Advances in Childhood Leukemia Consortium
Study SponsorTherapeutic Advances in Childhood Leukemia Consortium
CollaboratorsNot Provided
Investigators Study Chair: Heather Grossman, MD Children's Hopital New YorkPrincipal Investigator: Paul Gaynon, md Therapeutic Advances in Childhood Leukemia
Verification DateAugust 2010

Locations[ + expand ][ + ]

Phoenix Children's Hospital
Phoenix, Arizona, United States
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
University of Miami Cancer Center
Miami, Florida, United States, 33136
Children's Memorial
Chicago, Illinois, United States
Johns Hopkins University
Baltimore, Maryland, United States
C.S. Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109-0914
Childrens Hospital & Clinics of Minnesota
Minneapolis, Minnesota, United States, 55404-4597
University of Minnesota Children's Hospital
Minneapolis, Minnesota, United States
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
Nationwide Childrens Hospital
Columbus, Ohio, United States
Oregon Health and Science University
Portland, Oregon, United States
Vanderbilt Children's Hospital
Nashville, Tennessee, United States
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Hospital for Sick Kids
Toronto, Ontario, Canada