Analysis of Molecular Markers of Drug Resistance in Tumor Biopsies From Previously Untreated Aggressive Non-Hodgkin's Lymphoma

NCT ID: NCT00026910

Last Updated: 2008-03-04

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 1998-07-31
• Study Completion Date: 2002-05-31

Brief Summary

Although the cause(s) of clinical drug resistance in non-Hodgkin's lymphomas (NHL) are unknown, in vitro studies suggest that abnormalities of the cell cycle and mechanisms of apoptosis may play an important role. Clinical studies have now shown that p53, bcl-2 and tumor proliferation all have significant effects on clinical drug resistance. To further investigate the role of genes that control the cell cycle and apoptosis, we wish to correlate the expression of multiple molecular targets [including but not restricted to bcl-2, BAX, bcl-6, MIB-1, p53, p21, p27, p16, cyclin D(1), cyclin A, cyclin E, mdm-2, cpp 32, mcl-1, EBER-1, ALK, and a panel of B, T and other cell lineage markers], involving these pathways, with clinical outcome following treatment with combination chemotherapy. All clinical data and tissue samples for this study will come from patients who have been previously enrolled on two protocols for the initial treatment of aggressive lymphomas. No new patients will be enrolled for this study.

Detailed Description

Although the cause(s) of clinical drug resistance in non-Hodgkin's lymphomas (NHL) are unknown, in vitro studies suggest that abnormalities of the cell cycle and mechanisms of apoptosis may play an important role. Clinical studies have now shown that p53, bcl-2 and tumor proliferation all have significant effects on clinical drug resistance. To further investigate the role of genes that control the cell cycle and apoptosis, we wish to correlate the expression of multiple molecular targets using immunohistochemistry and cDNA microarray expression profiling (including but not restricted to bcl-2, BAX, bcl-6, MIB-1, p53, p21, p27, p16, cyclin D1, cyclin A, cyclin E, mdm-2, cpp 32, mcl-1, EBER-1, ALK, and a panel of B, T and other cell lineage markers), involving these pathways, with clinical outcome following treatment with combination chemotherapy. All clinical data and tissue samples for this study will come from patients who have been previously enrolled on two protocols for the initial treatment of aggressive lymphomas. No new patients will be enrolled for this study.

Conditions

Non-Hodgkin Lymphoma

Eligibility Criteria

Inclusion Criteria

Prior enrollment on the clinical trial of ProMACE-CytaBOM versus ProMACE-MOPP (81-C-0166) or Short Course ProMACE-CytaBOM (87-C-0180) for the treatment of previously untreated aggressive lymphomas.

Informed consent for participation in the above clinical trials.

Adequate biopsy material from initial biopsy and/or biopsies at relapse of disease.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Locations

National Cancer Institute (NCI)

Bethesda, Maryland, United States

Countries

United States

References

Harris CC, Hollstein M. Clinical implications of the p53 tumor-suppressor gene. N Engl J Med. 1993 Oct 28;329(18):1318-27. doi: 10.1056/NEJM199310283291807. No abstract available.

Reference Type: BACKGROUND

PMID: 8413413 (View on PubMed)

Wilson WH, Teruya-Feldstein J, Fest T, Harris C, Steinberg SM, Jaffe ES, Raffeld M. Relationship of p53, bcl-2, and tumor proliferation to clinical drug resistance in non-Hodgkin's lymphomas. Blood. 1997 Jan 15;89(2):601-9.

Reference Type: BACKGROUND

PMID: 9002964 (View on PubMed)

Sachs L, Lotem J. Control of programmed cell death in normal and leukemic cells: new implications for therapy. Blood. 1993 Jul 1;82(1):15-21.

Reference Type: BACKGROUND

PMID: 8324219 (View on PubMed)

Other Identifiers

98-C-0136

Identifier Type: -

Identifier Source: secondary_id

980136

Identifier Type: -

Identifier Source: org_study_id