Lymphoma, Non-HodgkinNCT01196520
Epidemiology of Burkitt Lymphoma in East Africa Children or Minors (EMBLEM)
An observational study of Lymphoma, Non-Hodgkin and Malaria, run by National Cancer Institute (NCI) at 6 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 15 yearsHealthy volunteers can take part
- Conditions the study is for
- Lymphoma, Non-Hodgkin, Malaria, Herpesvirus 4, Human
- How many people
- 4,893 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 25 May 2010to 21 May 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 15 years
- All sexes
- Healthy volunteers accepted
- Child
Study population: Residents of Northern Uganda, Western Kenya, and Northern Tanzania.
Who may be able to join
- 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.
Show all 9Show fewer
- For control subjects:
- Age 0-15 years.
- Residing in a defined geographic area for at least 4 months.
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
Uganda4 sites
St.Mary's Hospital Lacor
Gulu
Kuluva Hospital (Arua)
Kampala
Homabay District Hospital
Nyanza
Webuye District Hospital
Webuye
Tanzania2 sites
Bugando Medical Center
Mwanza
Shirati Health, Educational, and Development Foundation
Shirati
About this study
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.
...
Read the 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.
- Conditions
- Lymphoma, Non-Hodgkin, Malaria, Herpesvirus 4, Human
- Keywords
- Burkitt Lymphoma, Epstein-Barr Virus, Malaria
- Medical subject headings
- Lymphoma, Non-Hodgkin, Malaria, Epstein-Barr Virus Infections, Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
Burkitts Lymphoma
Newly diagnosed case of BL confirmed by histology or cytology.
Measured: At enrollment
Secondary outcomes (1)
Malaria
Positive diagnosis for parasitemia based on blood smear or antigenemia based on a rapid diagnostic test.
Measured: At enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2010 (estimated)
- Study start25 May 2010
- Primary completion31 Dec 2015
- Study completion21 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Lymphoma, Non-HodgkinStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 4,893 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Sam M Mbulaiteye, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01196520
- Sponsor's protocol ID
- 999910133
- Other IDs
- 10-C-N133
- Status last verified
- May 2020
- First submitted
- 4 Sep 2010
- Last updated
- 22 May 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
BURKITT D. A sarcoma involving the jaws in African children. Br J Surg. 1958 Nov;46(197):218-23. doi: 10.1002/bjs.18004619704. No abstract available.
PubMed 13628987Levine PH, Connelly RR, McKay FW. Burkitt's lymphoma in the USA: cases reported to the American Burkitt Lymphoma Registry compared with population-based incidence and mortality data. IARC Sci Publ. 1985;(60):217-24.
PubMed 4065946Burkitt D. Burkitt's lymphoma outside the known endemic areas of Africa and New Guinea. Int J Cancer. 1967 Nov 15;2(6):562-5. doi: 10.1002/ijc.2910020603. No abstract available.
PubMed 5582262
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epidemiology of Burkitt Lymphoma in East Africa Children or Minors (EMBLEM)
- ClinicalTrials.gov ID
- NCT01196520
- Acronym / sponsor ID
- 999910133
- Conditions
- Lymphoma, Non-Hodgkin, Malaria, Herpesvirus 4, Human
- Keywords
- Burkitt Lymphoma, Epstein-Barr Virus, Malaria
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 4,893 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 25 May 2010 (actual)
- Primary completion
- 31 Dec 2015 (actual)
- Study completion
- 21 May 2020 (actual)
- First posted
- 8 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
...
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 design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- Up to 15 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Residents of Northern Uganda, Western Kenya, and Northern Tanzania.
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Burkitts Lymphoma
Time frame: At enrollment
Newly diagnosed case of BL confirmed by histology or cytology.
1 secondary outcome
Malaria
Time frame: At enrollment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2020.
- Background: PubMed 13628987BURKITT D. A sarcoma involving the jaws in African children. Br J Surg. 1958 Nov;46(197):218-23. doi: 10.1002/bjs.18004619704. No abstract available.
- Background: PubMed 4065946Levine PH, Connelly RR, McKay FW. Burkitt's lymphoma in the USA: cases reported to the American Burkitt Lymphoma Registry compared with population-based incidence and mortality data. IARC Sci Publ. 1985;(60):217-24.
- Background: PubMed 5582262Burkitt D. Burkitt's lymphoma outside the known endemic areas of Africa and New Guinea. Int J Cancer. 1967 Nov 15;2(6):562-5. doi: 10.1002/ijc.2910020603. No abstract available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sam M Mbulaiteye, M.D. principal investigator
National Cancer Institute (NCI)
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Lymphoma, Non-Hodgkin and Malaria, run by National Cancer Institute (NCI) at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Uganda, Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Burkitts Lymphoma (time frame: At enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01196520, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2020.