Resistance to Methotrexate in Patients With Acute Lymphoblastic Leukemia in Relapse or Remission

Sponsor

Children's Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00899899

Collaborator

National Cancer Institute (NCI) (NIH)

135

Enrollment

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Studying samples of blood from patients with cancer in the laboratory may help doctors learn more about cancer and the development of drug resistance in patients.

PURPOSE: This laboratory study is looking at resistance to methotrexate in patients with acute lymphoblastic leukemia in relapse or remission.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Genetic: microarray analysis Genetic: reverse transcriptase-polymerase chain reaction Other: laboratory biomarker analysis

Detailed Description

OBJECTIVES:

Determine the mechanisms of intrinsic and acquired methotrexate resistance using in vitro assays of matched initial diagnosis, relapsed, and nonrelapsed (control) leukemic blast samples from patients with acute lymphoblastic leukemia in relapse or remission.
Determine if the mechanisms of acquired methotrexate resistance are related to dosage or timing of methotrexate administration or other clinical factors in these patients.

OUTLINE: Random samples of frozen leukemic blasts from relapsing patients at initial diagnosis and relapse are selected. A corresponding sample from nonrelapsing patients (control) at initial diagnosis is also randomly selected.

Reduced folate carrier (RFC) and dehydrofolate reductase (DHFR) expression is measured using a quantitative reverse transcriptase-polymerase chain reaction assay of prepared RNA. DHFR gene amplification is measured by a dot blot analysis of prepared DNA. Results of these assays are used to determine if a particular mechanism of acquired methotrexate resistance is associated with a particular subset of acute lymphoblastic leukemia patients. Data are collected regarding the actual timing and dosage of methotrexate received by each patient and are correlated with the mechanisms of resistance.

PROJECTED ACCRUAL: A total of 135 paired samples will be accrued for this study.

Study Design

Study Type:

Observational

Actual Enrollment :

135 participants

Observational Model:

Case-Only

Time Perspective:

Retrospective

Official Title:

A Study of the Mechanisms of Intrinsic and Acquired Methotrexate Resistance in Acute Lymphocytic Leukemia

Study Start Date :

Jun 1, 1998

Actual Primary Completion Date :

Mar 1, 2005

Actual Study Completion Date :

Apr 1, 2006

Outcome Measures

Primary Outcome Measures

Mechanisms of intrinsic and acquired methotrexate resistance []
Correlation of acquired methotrexate resistance with dosage or timing of methotrexate administration []
Correlation of acquired methotrexate resistance with other clinical factors []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Meets 1 of the following criteria:
Acute lymphoblastic leukemia (ALL) in relapse, including all risk groups and leukemia subtypes, with frozen leukemic blast samples stored from the time of initial diagnosis and relapse
Non-relapsing ALL (as control)