Response or Resistance to Chemotherapy in Young Patients With Acute Lymphoblastic Leukemia Treated With Methotrexate

Molecular Correlates of Methotrexate in Childhood ALL

This laboratory study is looking at response or resistance to chemotherapy in young patients with acute lymphoblastic leukemia treated with methotrexate. Studying samples of tumor tissue in the laboratory from patients with cancer may help doctors learn more about changes that occur in DNA and drug resistance in patients.

Study Overview

• Status: Completed
• Conditions: Childhood Acute Lymphoblastic Leukemia in Remission; Recurrent Childhood Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia
• Intervention / Treatment: Other: laboratory biomarker analysis

Detailed Description

OBJECTIVES:

I. Determine the molecular basis for human reduced folate carrier (hRFC) transcripts in B-precursor and T-cell acute lymphoblastic leukemia (ALL) blasts obtained from children with newly diagnosed ALL subsequently treated with methotrexate.

II. Correlate hRFC expression in these specimens with methotrexate transport and sensitivities.

III. Determine the roles of high frequency gene/transcript variants for hRFC as determinants of response and resistance to methotrexate in these patients.

IV. Determine the roles of multidrug resistance-associated proteins as determinants of response and resistance to methotrexate and mercaptopurine in these patients.

OUTLINE: This is a multicenter study.

Tumor diagnostic specimens from patients who subsequently failed therapy within 4 years of diagnosis or who did not fail therapy within 4 years of diagnosis (control patients) are obtained from the Children's Oncology Group cellbank. Specimens are studied for molecular determinants of human reduced folate carrier (hRFC) gene expression and gene sequence alterations using reverse transcriptase-polymerase chain reaction (RT-PCR), thymidylate synthase inhibition assay, Rnase protection assay, or 5'RACE. Multidrug resistance proteins are also studied by RT-PCR.

A certificate of confidentiality protecting the identity of research participants in this project has been issued by the National Cancer Institute.

• Study Type: Observational
• Enrollment (Anticipated): 150

Contacts and Locations

Study Locations

• United States
  • California
    • Arcadia, California, United States, 91006-3776
      • Children's Oncology Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Newly Diagnosed Patients with ALL treated with Methotrexate

Description

Inclusion Criteria:

• Diagnosis of B-precursor or T-cell acute lymphoblastic leukemia

  • Newly diagnosed disease subsequently treated with methotrexate
• Banked diagnostic blast specimens are available from Childrens Oncology Group (COG) cellbank

Study Plan

How is the study designed?

Design Details

• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Arm I; Tumor diagnostic specimens from patients who subsequently failed therapy within 4 years of diagnosis or who did not fail therapy within 4 years of diagnosis (control patients) are obtained from the Children's Oncology Group cellbank. Specimens are studied for molecular determinants of human reduced folate carrier (hRFC) gene expression and gene sequence alterations using reverse transcriptase-polymerase chain reaction (RT-PCR), thymidylate synthase inhibition assay, Rnase protection assay, or 5'RACE. Multidrug resistance proteins are also studied by RT-PCR.

Other: laboratory biomarker analysis; Correlative studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Molecular basis for human reduced folate carrier (hRFC) transcripts	Up to 4 years
Correlation of hRFC expression and methotrexate transport and sensitivities	Up to 4 years
High frequency gene/transcript variants for hRFC in relation to response and resistance to methotrexate	Up to 4 years
Multidrug resistance-associated proteins in relation to response and resistance to methotrexate and mercaptopurine	Up to 4 years

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Larry Matherly, Children's Oncology Group

Study record dates

Study Major Dates

• Study Start: November 1, 2003
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: May 9, 2009
• First Submitted That Met QC Criteria: May 9, 2009
• First Posted (Estimate): May 12, 2009

Study Record Updates

• Last Update Posted (Estimate): May 11, 2016
• Last Update Submitted That Met QC Criteria: May 9, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: AALL04B1; NCI-2009-00308 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CDR0000346452 (Other Identifier: Clinical Trials.gov); COG-AALL04B1 (Other Identifier: Children's Oncology Group); R01CA076641 (U.S. NIH Grant/Contract)