05-001: Treatment of Acute Lymphoblastic Leukemia in Children

Summary

RATIONALE: L-asparaginase is an important component of treatment for childhood acute lymphoblastic leukemia, but is also associated with notable side-effects, including hypersensitivity, pancreatitis, and thrombosis. We have previously reported that patients with acute lymphoblastic leukemia in whom asparaginase treatment was discontinued because of intolerable side-effects had survival outcomes that were inferior to those who received all or nearly all of their intended doses. Two bacterial sources of asparaginase exist: Escherichia coli (E coli) and Erwinia chrysanthemia (Erwinia). Generally, the E coli-derived enzyme has been used as front-line therapy and the Erwinia-derived preparation has been reserved for patients who develop hypersensitivity reactions. Pegylated E coli asparaginase (PEG-asparaginase) has a longer half-life and is potentially less immunogenic than native E coli L-asparaginase, and has been used as the initial asparaginase preparation in some pediatric acute lymphoblastic leukemia treatment regimens.

PURPOSE: Although the pharmacokinetics of each of these asparaginase preparations: intravenous PEG-asparaginase (IV-PEG) and intramuscular native E coli L-asparaginase (IM-EC) have been well characterized, their relative efficacy and toxicity have not been studied extensively.

Conditions

• Drug/Agent Toxicity by Tissue/Organ
• Leukemia

Interventions

DRUG

asparaginase

DRUG

cyclophosphamide

DRUG

cytarabine

DRUG

dexamethasone

DRUG

dexrazoxane hydrochloride

DRUG

doxorubicin hydrochloride

DRUG

etoposide

Given IV

DRUG

leucovorin calcium

DRUG

mercaptopurine

Given orally

DRUG

methotrexate

DRUG

methylprednisolone

DRUG

pegaspargase

Given IV

DRUG

prednisolone

DRUG

therapeutic hydrocortisone

DRUG

vincristine sulfate

RADIATION

radiation therapy

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• Dana-Farber Cancer Institute

  lead OTHER

Principal Investigators

• Lynda Vrooman, MD · Dana-Farber Cancer Institute

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

1 Year

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2005-04-30

Primary Completion

2014-08-31

Completion

2019-06-30

Countries

• United States
• Canada

Study Locations