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

May 21, 2020 updated by: National Cancer Institute (NCI)

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.

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Study Overview

Status

Completed

Conditions

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.

Study Type

Observational

Enrollment (Actual)

4893

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Tanzania
      • Mwanza, Tanzania
        • Bugando Medical Center
      • Shirati, Tanzania
        • Shirati Health, Educational, and Development Foundation
  • Uganda
      • Gulu, Uganda
        • St.Mary's Hospital Lacor
      • Kampala, Uganda
        • Kuluva Hospital (Arua)
      • Nyanza, Uganda
        • Homabay District Hospital
      • Webuye, Uganda
        • Webuye District Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 15 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Residents of Northern Uganda, Western Kenya, and Northern Tanzania.

Description

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
BL Cases
Children from East Africa diagnosed with BL
HCII Controls
Matched controls from the local health clinics
Population Controls
Matched controls from the geographic region

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Burkitts Lymphoma
Time Frame: At enrollment
Newly diagnosed case of BL confirmed by histology or cytology.
At enrollment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Malaria
Time Frame: At enrollment
Positive diagnosis for parasitemia based on blood smear or antigenemia based on a rapid diagnostic test.
At enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Sam M Mbulaiteye, M.D., National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 25, 2010

Primary Completion (Actual)

December 31, 2015

Study Completion (Actual)

May 21, 2020

Study Registration Dates

First Submitted

September 4, 2010

First Submitted That Met QC Criteria

September 4, 2010

First Posted (Estimate)

September 8, 2010

Study Record Updates

Last Update Posted (Actual)

May 22, 2020

Last Update Submitted That Met QC Criteria

May 21, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 999910133
  • 10-C-N133

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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