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

This study is currently recruiting participants.
Verified July 31, 2017 by National Institutes of Health Clinical Center (CC)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01196520
First Posted: September 8, 2010
Last Update Posted: October 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by:
National Institutes of Health Clinical Center (CC)
  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: Observational Model: Case-Control
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 ]
  • Malaria [ Time Frame: At enrollment ]

Estimated Enrollment: 6750
Study Start Date: May 24, 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 pathogenitically 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

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 15 Years   (Child)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
National Cancer Institute (NCI)
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
First Submitted: September 4, 2010
First Posted: September 8, 2010
Last Update Posted: October 6, 2017
Last Verified: July 31, 2017

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

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