Epidemiology of Burkitt Lymphoma in East Africa Children or Minors (EMBLEM)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01196520
First received: September 4, 2010
Last updated: May 28, 2014
Last verified: May 2014
  Purpose

Burkitt lymphoma (BL) is an aggressive monoclonal B-cell malignancy that is rare (sporadic) worldwide, but is 100-fold more common (endemic) in equatorial Africa, particularly among children. Epstein-Barr virus (EBV) and malaria are epidemiologically linked to endemic BL in epidemiologic studies, but questions remain about role of EBV variants and the evidence for association with malaria is weak. EBV is ubiquitous, yet only few children develop BL, possibly because only a few EBV variants are pathogenically relevant. The association of BL with malaria is based on ecologic and non-comparative clinical studies. Two case-control studies have reported significant association of high anti-malarial antibodies with BL (OR=5_ among children in Uganda and in Malawi, but selection bias (cases and controls came from dissimilar geographical areas) and reverse causality bias were limitations. Three studies were conducted in the 1960s and 70s to test association of carriage of malaria-resistance gene with BL, two of which reported a significant or marginal inverse association. These pioneering studies were small (240 cases all together) and looked at one polymorphism in one gene (sickle cell gene). Improvements in technologies to characterize genetic variation allow the EBV and malaria hypotheses to be examined with greater power by looking at genetic variation across multiple genes.

Epidemiology of Burkitt lymphoma in East African children and minors (EMBLEM) is a case-control study of 1500 BL cases and 3000 age-, sex- and residence-frequency matched controls we are proposing to conduct in East Africa. The study will enroll cases at four hospitals in four regions in East Africa, where malaria transmission is holoendemic and year round. The controls will be enrolled from general population attendees at Health Center II (HC-II) units where the cases originated. The primary study objectives are: 1) to test the hypothesis that genetic resistance to malaria is associated with a lower risk of BL, and 2) to use genome-wide association methods to discover genetic variation that may be associated with decreased or increased risk of BL. Because genetic variation conveys no information on actual exposure to malaria or EBV, in secondary analyses, we will use empiric epidemiological questionnaire and laboratory methods: a) to measure exposure to malaria and its association with BL, and b) to measure EBV variants and their association with BL. To examine issues related to bias and to obtain data to correct for deviations, we will also enroll 2250 population controls from 5% of the villages to obtain population distribution of key exposures variables. This data will be used to reweight the distribution in HC-II controls back to the general population.


Condition
Lymphoma, Non-Hodgkin
Malaria
Herpesvirus 4, Human

Study Type: Observational
Study Design: Time Perspective: Cross-Sectional
Official Title: Epidemiology of Burkitt Lymphoma in East Africa Children or Minors (EMBLEM)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Burkitts Lymphoma [ Time Frame: At enrollment ] [ Designated as safety issue: No ]
  • Malaria [ Time Frame: At enrollment ] [ Designated as safety issue: No ]

Estimated Enrollment: 6750
Study Start Date: May 2010
Detailed Description:

Burkitt lymphoma (BL) is an aggressive monoclonal B-cell malignancy that is rare (sporadic) worldwide, but is 100-fold more common (endemic) in equatorial Africa, particularly among children. Epstein-Barr virus (EBV) and malaria are epidemiologically linked to endemic BL in epidemiologic studies, but questions remain about role of EBV variants and the evidence for association with malaria is weak. EBV is ubiquitous, yet only few children develop BL, possibly because only a few EBV variants are pathogenically relevant. The association of BL with malaria is based on ecologic and non-comparative clinical studies. Two case-control studies have reported significant association of high anti-malarial antibodies with BL (OR=5_ among children in Uganda and in Malawi, but selection bias (cases and controls came from dissimilar geographical areas) and reverse causality bias were limitations. Three studies were conducted in the 1960s and 70s to test association of carriage of malaria-resistance gene with BL, two of which reported a significant or marginal inverse association. These pioneering studies were small (240 cases all together) and looked at one polymorphism in one gene (sickle cell gene). Improvements in technologies to characterize genetic variation allow the EBV and malaria hypotheses to be examined with greater power by looking at genetic variation across multiple genes.

The Epidemiology of Burkitt lymphoma in East African children and minors (EMBLEM) is a case-control study of 1500 BL cases and 3000 age-, sex- and residence-frequency matched controls we are proposing to conduct in East Africa. The study will enroll cases at four hospitals in four regions in East Africa, where malaria transmission is holoendemic and year round. The controls will be enrolled from general population attendees at Health Center II (HC-II) units where the cases originated. The primary study objectives are: 1) to test the hypothesis that genetic resistance to malaria is associated with a lower risk of BL, and 2) to use genome-wide association methods to discover genetic variation that may be associated with decreased or increased risk of BL. Because genetic variation conveys no information on actual exposure to malaria or EBV, in secondary analyses, we will use empiric epidemiological questionnaire and laboratory methods: a) to measure exposure to malaria and its association with BL, and b) to measure EBV variants and their association with BL. To examine issues related to bias and to obtain data to correct for deviations, we will also enroll 2250 population controls from 5% of the villages to obtain population distribution of key exposures variables. This data will be used to reweight the distribution in HC-II controls back to the general population.

  Eligibility

Ages Eligible for Study:   up to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

For case subjects:

  • Newly diagnosed child with BL. New newly diagnosed means not more than 1 month since diagnosis, to minimize bias from mortality after diagnosis.
  • Not initiated BL specific treatment.
  • Age 0 through 15 years at diagnosis.
  • Residing in a pre-defined geographic area for at least 4 months prior to onset of BL-related symptoms. The catchment geographic area will be defined in the Study Manual as districts for each region.
  • Diagnosis based on local histology or cytology report.

For control subjects:

  • Age 0-15 years.
  • Residing in a defined geographic area for at least 4 months.

EXCLUSION CRITERIA:

For case subjects:

  • Not residing within the pre-defined geographic area for at least 4 months before onset of BL-related symptoms.
  • Clinically unstable condition; they will be stabilized first.
  • Initiated BL treatment.
  • Wrong diagnosis.
  • Refusal or are inability to consent.

For control subjects:

  • Mild clinical malaria (fever 37.5 degrees Celcius and a thick blood smear positive for malaria).
  • Any severe illness requiring immediate admission to hospital, e.g. acute respiratory infection, diarrhea with dehydration, snake bites or fractures.
  • Any cancer.
  • Not a usual resident of an eligible geographic area.
  • Non-consent.
  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: NCT01196520

Contacts
Contact: Sam M Mbulaiteye, M.D. (301) 594-7825 mbulaits@mail.nih.gov

Locations
Tanzania
Bugando Medical Center Recruiting
Mwanza, Tanzania
Shirati Health, Educational, and Development Foundation Recruiting
Shirati, Tanzania
Uganda
St.Mary's Hospital Lacor Recruiting
Gulu, Uganda
Kuluva Hospital (Arua) Recruiting
Kampala, Uganda
Homabay District Hospital Recruiting
Nyanza, Uganda
Webuye District Hospital Recruiting
Webuye, Uganda
Sponsors and Collaborators
Investigators
Principal Investigator: Sam M Mbulaiteye, M.D. National Cancer Institute (NCI)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT01196520     History of Changes
Other Study ID Numbers: 999910133, 10-C-N133
Study First Received: September 4, 2010
Last Updated: May 28, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Burkitt Lymphoma
Epstein-Barr Virus
Malaria

Additional relevant MeSH terms:
Burkitt Lymphoma
Malaria
Lymphoma, Non-Hodgkin
Lymphoma
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Neoplasms by Histologic Type
Neoplasms
Lymphoma, B-Cell
Neoplasms, Experimental
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Protozoan Infections
Parasitic Diseases

ClinicalTrials.gov processed this record on September 16, 2014