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

Completed

• Conditions: B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Recurrent Childhood Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia
• Interventions: Other: laboratory biomarker analysis

• Registration Number: NCT00898404
• Lead Sponsor: Children's Oncology Group

Brief Summary

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.

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 Timeline

• Study Start: 2003-11
• Study First Submitted: 2009-05-09
• Study First Submitted QC: 2009-05-09
• Study First Posted: 2009-05-12
• Status Verified: 2016-05
• Primary Completion: 2016-05
• Study Completion: 2016-05
• Last Update Submitted: 2016-05-09
• Last Update Posted: 2016-05-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Arm I	laboratory biomarker analysis	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.

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Children's Oncology Group; 🇺🇸 Arcadia, California, United States