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

This study has been completed.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group Identifier:
First received: May 9, 2009
Last updated: September 28, 2015
Last verified: May 2015

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 Intervention
Genetic: microarray analysis
Genetic: reverse transcriptase-polymerase chain reaction
Other: laboratory biomarker analysis

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Retrospective
Official Title: A Study of the Mechanisms of Intrinsic and Acquired Methotrexate Resistance in Acute Lymphocytic Leukemia

Resource links provided by NLM:

Further study details as provided by Children's Oncology Group:

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

Enrollment: 135
Study Start Date: June 1998
Study Completion Date: April 2006
Primary Completion Date: March 2005 (Final data collection date for primary outcome measure)
Detailed Description:


  • 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.


Ages Eligible for Study:   up to 120 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Acute lymphoblastic leukemia (ALL) in relapse


  • 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)


  • Not specified


  • Not specified
  Contacts and Locations
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Please refer to this study by its identifier: NCT00899899

Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Study Chair: Richard Gorlick, MD Children's Hospital at Montefiore
  More Information

Responsible Party: Children's Oncology Group Identifier: NCT00899899     History of Changes
Other Study ID Numbers: B977
COG-B977 ( Other Identifier: Children's Oncology Group )
CDR0000078589 ( Other Identifier: Clinical )
Study First Received: May 9, 2009
Last Updated: September 28, 2015

Keywords provided by Children's Oncology Group:
adult acute lymphoblastic leukemia in remission
childhood acute lymphoblastic leukemia in remission
recurrent adult acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors processed this record on May 23, 2017