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

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00899899
• Other study ID #: B977
• Secondary ID: COG-B977CDR00000
• Status: Completed
• Phase: N/A
• First received: May 9, 2009
• Last updated: September 28, 2015
• Start date: June 1998
• Est. completion date: April 2006

Study information

• Verified date: May 2015
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 135
• Est. completion date: April 2006
• Est. primary completion date: March 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 120 Years

Eligibility

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

Study Design

Observational Model: Case-Only, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Genetic:
• microarray analysis

• reverse transcriptase-polymerase chain reaction

Other:
• laboratory biomarker analysis

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mechanisms of intrinsic and acquired methotrexate resistance			No
Primary	Correlation of acquired methotrexate resistance with dosage or timing of methotrexate administration			No
Primary	Correlation of acquired methotrexate resistance with other clinical factors			No