Genome Expression in Lymphoma, Leukemia and Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Collaborator:
Lymphoma/Leukemia Molecular Profiling Project (LLMPP)
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00339963
First received: June 19, 2006
Last updated: March 14, 2014
Last verified: December 2013
  Purpose

This study will use genomics-based technology, such as DNA microarrays, to more precisely diagnose subsets of lymphoma, leukemia and multiple myeloma patients. There have been many attempts to classify lymphoid cancers in ways that will be useful for clinical diagnosis and treatment. Although broad diagnostic categories have been reliably defined, patients within each category have distinct clinical courses, suggesting that these classifications could be further divided into molecular (genetic) subtypes. For example, 40 percent of patients with diffuse large B-cell lymphoma achieve long-term disease remissions following combination chemotherapy and are apparently cured, whereas the remaining 60 percent die from the disease. Similarly, some patients with follicular lymphoma develop aggressive disease within a few years of diagnosis, while others have stable disease over 10 to 20 years. Although the distinctions in clinical course of these diseases are recognized, there are no studies to determine the molecular (genetic) basis for this variability. This study will try to define new molecular diagnostic categories in these diseases and correlate them with clinical features, including treatment response, disease remission and overall survival following chemotherapy.

This retrospective study will use clinical data and tissue samples from participating centers in the Lymphoma/Leukemia Molecular Profiling Project LLMPP). New patients will not be recruited for this study.

Biopsy materials, including fresh frozen or OTC-embedded lymphoma biopsy material, viably frozen samples of peripheral blood cells from leukemia patients, and viably frozen samples of bone marrow aspirates from multiple myeloma patients will be collected from pathologists participating in the LLMPP. RNA and genomic DNA will be extracted from the tumor samples. A variety of technologies will be used to characterize the genome of the cancer cells, including lymphochip microarrays for array-based comparative genomic hybridization; Southern blotting and PCR for translocation of genes previously implicated in these malignancies; and PCR and DNA sequencing methods for analyzing base changes in the genome of the cancer cells. Clinical information from the initial diagnosis to disease relapse will be taken from existing databases and/or patient charts. Gene expression will be correlated with the clinical data. If a small number of genes is found to strongly predict clinical outcome, quantitative RT-PCR assays using the Taqman technology may be developed as an alternative to DNA microarray analysis.


Condition
Lymphoma
Leukemia
Multiple Myeloma
Lymphoid Malignancies

Study Type: Observational
Official Title: Expression of the Genome in Lymphoid Malignancies

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 3000
Study Start Date: November 2001
Detailed Description:

Current diagnosis of the lymphoid malignancies relies upon the morphological appearance of the cancer cells supplemented by a few molecular markers. Within a diagnostic category, the clinical courses and responses of patients to therapy are variable, suggesting that the existing diagnostic categories may harbor more than one disease entity. Recent genomic technologies allow a comprehensive molecular analysis of the expression of the genome in cancer cells. DNA microarray analysis of gene expression in lymphomas revealed distinct molecular subtypes of diffuse large B-cell lymphoma and these new molecularly-defined lymphoma subtypes had divergent clinical outcomes. To extend our genomic analysis to all lymphoid malignancies, we have formed a consortium of cooperating institutions termed the Lymphoma/Leukemia Molecular Profiling Project (LLMPP). The clinical centers participating in the LLMPP will send lymphoma, leukemia and multiple myeloma samples to the NCI for gene expression profiling, array-based comparative genomic hybridization and cancer gene resequencing. Clinical data will also be sent for the patients in this study for the purpose of correlating gene expression measurements with clinical outcome. The goals of this effort are to define new molecular diagnostic categories in these diseases that are clinically relevant and to gain new insight into the molecular pathways that are active in these malignancies. The home institutions providing clinical data and tissue samples have obtained local approval by their clinical research committees for this study. No new patients will be enrolled or biopsied for this study.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Diagnosis of lymphoid malignancy at one of the LLMPP participating institutions, including specimens originating at other clinical sites and submitted to LLMPP participating sites.

Informed consent for research studies performed on biopsy material or waiver of the requirement for informed consent by the clinical research review boards at the LLMPP institutions.

Sufficient frozen biopsy and/or FFPE material from initial biopsy and/or biopsies at relapse of disease to obtain adequate RNA and DNA for gene expression profiling and analysis of genomic alterations in the malignant cells.

  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: NCT00339963

Contacts
Contact: Louis M Staudt, M.D. (301) 402-1892 lstaudt@mail.nih.gov

Locations
United States, Maryland
National Cancer Institute (NCI), 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: Deborah Draper    301-435-8525    draperde@mail.nih.gov   
Sponsors and Collaborators
Lymphoma/Leukemia Molecular Profiling Project (LLMPP)
Investigators
Principal Investigator: Louis M Staudt, M.D. National Cancer Institute (NCI)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00339963     History of Changes
Other Study ID Numbers: 999902042, 02-C-N042
Study First Received: June 19, 2006
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Microarray
Lymphoma
Leukemia
Myeloma
Profiling
Gene Expression
Molecular Diagnosis
Prognosis
Lymphoid Malignancy

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms
Lymphoma
Leukemia
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Lymphatic Diseases

ClinicalTrials.gov processed this record on September 15, 2014