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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00899899
Recruitment Status : Completed
First Posted : May 12, 2009
Last Update Posted : September 30, 2015
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

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

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.

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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 : June 1998
Actual Primary Completion Date : March 2005
Actual Study Completion Date : April 2006

Primary Outcome Measures :
  1. Mechanisms of intrinsic and acquired methotrexate resistance
  2. Correlation of acquired methotrexate resistance with dosage or timing of methotrexate administration
  3. Correlation of acquired methotrexate resistance with other clinical factors

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   up to 120 Years   (Child, Adult, Older Adult)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00899899

Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
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Study Chair: Richard Gorlick, MD Children's Hospital at Montefiore
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Responsible Party: Children's Oncology Group Identifier: NCT00899899    
Other Study ID Numbers: B977
COG-B977 ( Other Identifier: Children's Oncology Group )
CDR0000078589 ( Other Identifier: Clinical )
First Posted: May 12, 2009    Key Record Dates
Last Update Posted: September 30, 2015
Last Verified: May 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:
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases