Clinical trial NCT00898404: Response or Resistance to Chemotherapy in Young Patients With Acute Lymphoblastic Leukemia Treated With Methotrexate
Official title: Molecular Correlates of Methotrexate in Childhood ALL
Study type: OBSERVATIONAL
Overall status: 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
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-05-12
Enrollment: 150
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Newly Diagnosed Patients with ALL treated with Methotrexate

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.

Eligibility criteria: 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

Primary outcomes:
measure: Molecular basis for human reduced folate carrier (hRFC) transcripts
timeFrame: Up to 4 years
measure: Correlation of hRFC expression and methotrexate transport and sensitivities
timeFrame: Up to 4 years
measure: High frequency gene/transcript variants for hRFC in relation to response and resistance to methotrexate
timeFrame: Up to 4 years
measure: Multidrug resistance-associated proteins in relation to response and resistance to methotrexate and mercaptopurine
timeFrame: Up to 4 years
Secondary outcomes:
Other outcomes:
Locations:
city: Arcadia
country: United States
facility: Children's Oncology Group
state: California
Study officials:
affiliation: Children's Oncology Group
name: Larry Matherly
role: PRINCIPAL_INVESTIGATOR
References: