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

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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT00899899

Enrollment

135

Registered

2009-05-12

Start date

1998-06-30

Completion date

2006-04-30

Last updated

2015-09-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Leukemia

Keywords

adult acute lymphoblastic leukemia in remission, childhood acute lymphoblastic leukemia in remission, recurrent adult acute lymphoblastic leukemia, recurrent childhood acute lymphoblastic leukemia

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.

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.

Interventions

GENETICmicroarray analysis

GENETICreverse transcriptase-polymerase chain reaction

OTHERlaboratory biomarker analysis

Study design

Observational model

CASE_ONLY

Time perspective

RETROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

No minimum to 120 Years

Healthy volunteers

Inclusion criteria

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) PATIENT CHARACTERISTICS: * Not specified PRIOR CONCURRENT THERAPY: * Not specified

Design outcomes

Primary

Measure	Time frame
Correlation of acquired methotrexate resistance with other clinical factors	—
Mechanisms of intrinsic and acquired methotrexate resistance	—
Correlation of acquired methotrexate resistance with dosage or timing of methotrexate administration	—

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026