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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Children's Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00898404
First received: May 9, 2009
Last updated: July 9, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention
B-cell Childhood Acute Lymphoblastic Leukemia
Childhood Acute Lymphoblastic Leukemia in Remission
Recurrent Childhood Acute Lymphoblastic Leukemia
T-cell Childhood Acute Lymphoblastic Leukemia
Other: laboratory biomarker analysis

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Molecular Correlates of Methotrexate in Childhood ALL

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Molecular basis for human reduced folate carrier (hRFC) transcripts [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • Correlation of hRFC expression and methotrexate transport and sensitivities [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • High frequency gene/transcript variants for hRFC in relation to response and resistance to methotrexate [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • Multidrug resistance-associated proteins in relation to response and resistance to methotrexate and mercaptopurine [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: November 2003
Estimated Primary Completion Date: January 2100 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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

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

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Newly Diagnosed Patients with ALL treated with Methotrexate

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00898404

Locations
United States, California
Children's Oncology Group Recruiting
Arcadia, California, United States, 91006-3776
Contact: Larry H. Matherly    313-832-7294    matherly@kci.wayne.edu   
Principal Investigator: Larry H. Matherly         
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Larry Matherly Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00898404     History of Changes
Other Study ID Numbers: AALL04B1, NCI-2009-00308, CDR0000346452, COG-AALL04B1, R01CA076641
Study First Received: May 9, 2009
Last Updated: July 9, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 27, 2014