Contiguous Stage II Adult Diffuse Large Cell LymphomaPhase 2NCT00121199
Combination Chemo, Rituximab, and Bevacizumab in Older Patients With Stage II-IV Diffuse Large B-Cell Lymphoma
A Phase 2 study testing rituximab, bevacizumab and cyclophosphamide in people with Contiguous Stage II Adult Diffuse Large Cell Lymphoma and Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase II trial is studying how well giving combination chemotherapy together with rituximab and bevacizumab works in treating older patients with stage II, stage III, or stage IV diffuse large B-cell lymphoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Contiguous Stage II Adult Diffuse Large Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, Stage III Adult Diffuse Large Cell Lymphoma
- What is being tested?
- rituximab, bevacizumab and cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 73 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2005to Dec 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients must have previously untreated Stage III, IV, or bulky Stage II diffuse large B-cell non-Hodgkin's lymphoma which is positive for CD20; a report providing confirmation of CD20 expression must be submitted
- Pathology Review: Adequate sections from the original diagnostic specimen must be available for submission for review by the SWOG Lymphoma Pathology Laboratory; an adequate biopsy requires sufficient tissue to establish the architecture and a REAL or WHO histologic subtype with certainty; thus, core biopsies, especially multiple core biopsies may be adequate; whereas, needle aspirations or cytologies are not adequate
- Specimens for analysis of angiogenic markers must be submitted to the University of Arizona
- All patients must have bidimensionally measurable disease documented within 28 days prior to registration; patients with non-measurable disease in addition to measurable disease must have all nonmeasurable disease assessed within 42 days prior to registration
- Patients must have a unilateral or bilateral bone marrow aspirate and biopsy performed within 42 days prior to registration
- Patients must have a CT scan of the chest/abdomen and pelvis performed within 28 days prior to registration
Show all 32Show fewer
- Patients must not have clinical evidence of central nervous system involvement by lymphoma; any laboratory or radiographic tests performed to assess CNS involvement must be negative within 42 days of registration
- Patients may not have a previous diagnosis of indolent lymphoma (histologic transformation or mixed histologies with an indolent or nodular component are ineligible)
- Patients must not have received prior chemotherapy, radiation, or antibody-based therapy for lymphoma
- Patients must have a Zubrod performance status of 0 - 2
- Serum LDH must be measured within 28 days prior to registration
- Patients must have a cardiac ejection fraction >= 45% by MUGA scan or a 2-d ECHO with no significant abnormalities within 42 days prior to registration
- Absolute neutrophil count > 1,000/mcL obtained within 28 days prior to registration
- Platelet count > 100,000/mcL obtained within 28 days prior to registration
- Serum creatinine < 2 x the institutional upper limit of normal within 28 days prior to registration
- Patients must have urine proteinuria screened by dipstick or urine analysis within 28 days prior to registration; in patients with proteinuria >= +1 or urine protein:creatinine ratio >= 1.0, a 24 hour urine protein should be obtained and the level < 1gm/24 hours to be eligible
- Patients must not have a history of hypersensitivity reaction to products containing Polysorbate 20 (Tween 20), Chinese hamster ovary cell products, or recombinant human antibodies
- Patients known to be HIV-positive, or who have a history of solid organ transplantation are ineligible due to the concern over immunosuppression associated with B-cell depletion; patients at high risk of Hepatitis B virus infection should be screened before initiation of rituximab
- Patients must not have uncontrolled hypertension
- Patients with a history of prior myocardial infarction, unstable angina, stroke, or arterial thrombosis within 6 months are ineligible
- Patients with clinically significant peripheral vascular disease, a serious or non-healing wound, ulcer, or bone fracture, or a bleeding diathesis/coagulopathy are ineligible
- Patients with a history of venous thrombosis requiring full-dose anticoagulation or currently receiving anticoagulation therapy may be eligible provided that the following criteria are met:
- The patient must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin or on a stable dose of LMW heparin
- The patient must not have bleeding or pathological conditions that carry a high risk of bleeding (e.g. tumor involving major vessels, known varices)
- Patients who have had a major surgical procedure or traumatic injury within 28 days prior to registration or anticipation of major surgical procedure during the course of therapy are ineligible
- Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months are ineligible
- Patients requiring continuous supplemental oxygen therapy are ineligible
- No prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer for which the patient has been disease-free for five years
- Pregnant or nursing women may not participate in this study due to the potential for congenital abnormalities, and of harm to nursing infants due to this treatment regimen; women or men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during the study period and for at least 6 months after the completion of therapy
- If Day 28 or 42 falls on a weekend or holiday, the limit may be extended to the next working day
- Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
- At the time of patient registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Trial of Standard Dose Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP) and Rituximab Plus Bevacizumab for Advanced Stage Diffuse Large B-Cell NHL
This phase II trial is studying how well giving combination chemotherapy together with rituximab and bevacizumab works in treating older patients with stage II, stage III, or stage IV diffuse large B-cell lymphoma. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Monoclonal antibodies, such as rituximab and bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Bevacizumab may also stop the growth of cancer cells by blocking blood flow to the cancer. Giving combination chemotherapy together with monoclonal antibodies may kill more cancer cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To estimate the 1-year progression-free survival rate in patients with advanced stage diffuse large B-cell NHL treated with CHOP - rituximab - bevacizumab.
II. To estimate the response rate (complete, complete unconfirmed, and partial) and 2-year progression-free survival of this regimen in patients with advanced stage diffuse large B-cell NHL.
III. To evaluate the toxicities associated with this regimen. IV. To correlate angiogenic biomarkers with patient outcome.
OUTLINE: This is a multicenter study.
Patients receive rituximab IV, bevacizumab IV over 30-90 minutes, cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1. Patients also receive oral prednisone on days 1-5. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at least every 6 months for 2 years and then annually for 3 years.
- Conditions
- Contiguous Stage II Adult Diffuse Large Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, Stage III Adult Diffuse Large Cell Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma
- Being tested
- rituximab, bevacizumab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rituximabBiological
Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8
Given IV
bevacizumabBiological
Also called anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF
Given IV
cyclophosphamideDrug
Also called CPM, CTX, Cytoxan, Endoxan
Given IV
Also called ADM, ADR, Adria, Adriamycin PFS
Given IV
Also called leurocristine sulfate, VCR, Vincasar PFS
Given IV
prednisoneDrug
Also called DeCortin, Deltra
Given PO
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (CHOP, rituximab, bevacizumab) | Experimental | Patients receive rituximab IV, bevacizumab IV over 30-90 minutes, cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1. Patients also receive oral prednisone on days 1-5. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. Receives: Biological: rituximab; Biological: bevacizumab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: vincristine sulfate; Drug: prednisone; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival at 1 Year
Measured from time of registration to date of of first observation of progression/relapse, or death due to any cause, or last contact date
Measured: 0-1 year
Progression-free Survival at 2 Year
Measured from time of registration to date of of first observation of progression/relapse, or death due to any cause, or last contact date
Measured: 0-2 years
Secondary outcomes (2)
Objective Response (Confirmed and Unconfirmed Complete Response (CR) or Partial Response (PR))
Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the SPD for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.
Measured: After Cycle 4 (Day 64) but prior to Cycle 5 (Day 85) and after Cycle 8 (Day 181). After completion of protocol treatment, every 6 months for 2 years, then annually for a maximum of five years.
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug
Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
Measured: Patients were assessed for adverse events after every cycle (1 cycle = 21 days) of protocol treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2005 (estimated)
- Study startJun 2005
- Primary completionDec 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Contiguous Stage II Adult Diffuse Large Cell LymphomaStudies 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Alison Stopeck, Principal investigator, SWOG Cancer Research Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00121199
- Sponsor's protocol ID
- NCI-2012-03062
- Other IDs
- NCI-2012-03062, S0515, S0515, U10CA032102
- Status last verified
- Dec 2012
- First submitted
- 19 Jul 2005
- Last updated
- 21 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Stopeck AT, Unger JM, Rimsza LM, LeBlanc M, Farnsworth B, Iannone M, Glenn MJ, Fisher RI, Miller TP. A phase 2 trial of standard-dose cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and rituximab plus bevacizumab for patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: SWOG 0515. Blood. 2012 Aug 9;120(6):1210-7. doi: 10.1182/blood-2012-04-423079. Epub 2012 Jun 25.
PubMed 22734071
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Standard Dose Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP) and Rituximab Plus Bevacizumab for Advanced Stage Diffuse Large B-Cell NHL
- ClinicalTrials.gov ID
- NCT00121199
- Acronym / sponsor ID
- NCI-2012-03062
- Conditions
- Contiguous Stage II Adult Diffuse Large Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, Stage III Adult Diffuse Large Cell Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 73 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jun 2005
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 21 Jul 2005 (estimated)
- Results
- Posted 19 Dec 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying how well giving combination chemotherapy together with rituximab and bevacizumab works in treating older patients with stage II, stage III, or stage IV diffuse large B-cell lymphoma. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Monoclonal antibodies, such as rituximab and bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Bevacizumab may also stop the growth of cancer cells by blocking blood flow to the cancer. Giving combination chemotherapy together with monoclonal antibodies may kill more cancer cells.
Detailed description
PRIMARY OBJECTIVES:
- To estimate the 1-year progression-free survival rate in patients with advanced stage diffuse large B-cell NHL treated with CHOP - rituximab - bevacizumab.
II. To estimate the response rate (complete, complete unconfirmed, and partial) and 2-year progression-free survival of this regimen in patients with advanced stage diffuse large B-cell NHL.
III. To evaluate the toxicities associated with this regimen. IV. To correlate angiogenic biomarkers with patient outcome.
OUTLINE: This is a multicenter study.
Patients receive rituximab IV, bevacizumab IV over 30-90 minutes, cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1. Patients also receive oral prednisone on days 1-5. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at least every 6 months for 2 years and then annually for 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (CHOP, rituximab, bevacizumab) | Experimental | Biological: rituximab, Biological: bevacizumab, Drug: cyclophosphamide, Drug: doxorubicin hydrochloride, Drug: vincristine sulfate, Drug: prednisone, Other: laboratory biomarker analysisPatients receive rituximab IV, bevacizumab IV over 30-90 minutes, cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1. Patients also receive oral prednisone on days 1-5. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (32 listed)
- All patients must have previously untreated Stage III, IV, or bulky Stage II diffuse large B-cell non-Hodgkin's lymphoma which is positive for CD20; a report providing confirmation of CD20 expression must be submitted
- Pathology Review: Adequate sections from the original diagnostic specimen must be available for submission for review by the SWOG Lymphoma Pathology Laboratory; an adequate biopsy requires sufficient tissue to establish the architecture and a REAL or WHO histologic subtype with certainty; thus, core biopsies, especially multiple core biopsies may be adequate; whereas, needle aspirations or cytologies are not adequate
- Specimens for analysis of angiogenic markers must be submitted to the University of Arizona
- All patients must have bidimensionally measurable disease documented within 28 days prior to registration; patients with non-measurable disease in addition to measurable disease must have all nonmeasurable disease assessed within 42 days prior to registration
- Patients must have a unilateral or bilateral bone marrow aspirate and biopsy performed within 42 days prior to registration
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rituximabAlso: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8Given IV | Biological | Treatment (CHOP, rituximab, bevacizumab) |
| bevacizumabAlso: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGFGiven IV | Biological | Treatment (CHOP, rituximab, bevacizumab) |
| cyclophosphamideAlso: CPM, CTX, Cytoxan, EndoxanGiven IV | Drug | Treatment (CHOP, rituximab, bevacizumab) |
| doxorubicin hydrochlorideAlso: ADM, ADR, Adria, Adriamycin PFSGiven IV | Drug | Treatment (CHOP, rituximab, bevacizumab) |
| vincristine sulfateAlso: leurocristine sulfate, VCR, Vincasar PFSGiven IV | Drug | Treatment (CHOP, rituximab, bevacizumab) |
| prednisoneAlso: DeCortin, DeltraGiven PO | Drug | Treatment (CHOP, rituximab, bevacizumab) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (CHOP, rituximab, bevacizumab) |
Primary outcome
Progression-free Survival at 1 Year
Time frame: 0-1 year
Measured from time of registration to date of of first observation of progression/relapse, or death due to any cause, or last contact date
Progression-free Survival at 2 Year
Time frame: 0-2 years
Measured from time of registration to date of of first observation of progression/relapse, or death due to any cause, or last contact date
2 secondary outcomes
Objective Response (Confirmed and Unconfirmed Complete Response (CR) or Partial Response (PR))
Time frame: After Cycle 4 (Day 64) but prior to Cycle 5 (Day 85) and after Cycle 8 (Day 181). After completion of protocol treatment, every 6 months for 2 years, then annually for a maximum of five years.
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug
Time frame: Patients were assessed for adverse events after every cycle (1 cycle = 21 days) of protocol treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22734071Stopeck AT, Unger JM, Rimsza LM, LeBlanc M, Farnsworth B, Iannone M, Glenn MJ, Fisher RI, Miller TP. A phase 2 trial of standard-dose cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and rituximab plus bevacizumab for patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: SWOG 0515. Blood. 2012 Aug 9;120(6):1210-7. doi: 10.1182/blood-2012-04-423079. Epub 2012 Jun 25.
Related trials for Contiguous Stage II Adult Diffuse Large Cell Lymphoma
RecruitingObservational study
Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer
Chronic Myeloproliferative Disorders, Leukemia
Active, not recruitingObservational study
Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant
Hematopoietic/Lymphoid Cancer, Accelerated Phase Chronic Myelogenous Leukemia
Active, not recruiting
3'-Deoxy-3'-[18F] Fluorothymidine PET Imaging in Patients With Cancer
Brain and Central Nervous System Tumors, Chronic Myeloproliferative Disorders
RecruitingObservational study
Registry of Older Patients With Cancer
Chronic Myeloproliferative Disorders, Cognitive/Functional Effects
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.
Alison Stopeck principal investigator
SWOG Cancer Research Network
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing rituximab, bevacizumab and cyclophosphamide in people with Contiguous Stage II Adult Diffuse Large Cell Lymphoma and Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
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 32 inclusion and 0 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 21 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Progression-free Survival at 1 Year (time frame: 0-1 year). The study lists 2 primary outcomes in all. 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 NCT00121199, which also lists 1 linked publication.
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 21 May 2014.