Clinical trial NCT00899899: Resistance to Methotrexate in Patients With Acute Lymphoblastic Leukemia in Relapse or Remission
Official title: A Study of the Mechanisms of Intrinsic and Acquired Methotrexate Resistance in Acute Lymphocytic Leukemia
Study type: OBSERVATIONAL
Overall status: COMPLETED
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
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-05-12
Enrollment: 135
Sex: ALL
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Acute lymphoblastic leukemia (ALL) in relapse

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.

Eligibility 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

Primary outcomes:
measure: Mechanisms of intrinsic and acquired methotrexate resistance
measure: Correlation of acquired methotrexate resistance with dosage or timing of methotrexate administration
measure: Correlation of acquired methotrexate resistance with other clinical factors
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Children's Hospital at Montefiore
name: Richard Gorlick, MD
role: STUDY_CHAIR
References: