Stage III Diffuse Large B-Cell LymphomaPhase 2NCT02530125
Pidilizumab in Treating Patients With Stage III-IV Diffuse Large B-Cell Lymphoma Following First Remission
A Phase 2 study testing Laboratory Biomarker Analysis and Pidilizumab in people with Stage III Diffuse Large B-Cell Lymphoma and Stage IV Diffuse Large B-Cell Lymphoma, run by Northwestern University at 2 sites in United States.
Trial summary
The purpose of this study is to evaluate pidilizumab and its effect, bad and/or good, on the immune system in relation to its ability to fight cancer cells. Many cancers can be brought to a phase called complete remission (no cancer is found) but have a chance that they may come back. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage III Diffuse Large B-Cell Lymphoma, Stage IV Diffuse Large B-Cell Lymphoma
- What is being tested?
- Laboratory Biomarker Analysis and Pidilizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2015to Jan 2017
- 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
- Histologically confirmed de novo DLBCL by the 4th edition of the World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues published in 2008; patients with transform lymphoma are excluded; patients with known primary mediastinal large B-cell lymphoma (PMLBCL) are excluded; patients with known c-v-myc avian myelocytomatosis viral oncogene homolog (c-myc) translocation (by fluorescence in situ hybridization) positive DLBCL are eligible for enrollment; c-myc testing prior to study enrollment is not required; availability of diagnostic biopsy samples in encouraged for the exploratory analysis but not required for enrollment; patients with "double-hit" or "triple-hit" lymphoma are eligible for enrollment
- Previously completed anthracycline-based induction chemotherapy with standard regimens including rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP), dose adjusted (DA)-etoposide, prednisone, vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide (EPOCH), and rituximab (R), and R-hyper cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, methotrexate, and cytarabine (CVAD); patients need a minimum of 6 cycles of treatment; initial treatment with pidilizumab must be administered between 30-90 days from last dose of induction chemotherapy
- Complete remission (CR) according to the Revised Response Criteria for Malignant Lymphoma after first-line treatment
- Diagnostic CT scans with contrast of chest, abdomen, and pelvis must have been performed within 8 weeks from the first day of the last cycle of R-chemotherapy; a neck CT will be required if the patient had involvement of the neck region at initial diagnosis
- A negative fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/CT scan performed within 8 weeks from the first day of the last cycle of R-chemotherapy and confirming CR, with negative defined as a score of 1-3 on the Deauville 5-point scale used to quantify radionucleotide density in PET scans as determined locally; PET positive/indeterminate lesions which are confirmed on biopsy to harbor no active lymphoma will be considered negative for determination of CR status
- If positive bone marrow involvement at initial diagnosis the patient must have a negative bone marrow biopsy following R-chemotherapy to confirm the CR
Show all 18Show fewer
- Stage III/IV disease by Ann Arbor Staging
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Any National Comprehensive Cancer Network (NCCN)-International Prognostic Index (IPI) score; a calculated score required for enrollment
- Absolute neutrophil count (ANC) >= 1000
- Platelet count >= 50,000
- Total bilirubin =< 2 x upper limit of normal (ULN) or if total bilirubin is > 2 x ULN, the direct bilirubin must be normal
- Alkaline (Alk.) phosphatase =< 3 x ULN
- Aspartate aminotransferase (AST) =< 3 x ULN
- Creatinine =< 2 x ULN or creatinine clearance (CrCl) > 30 ml/min
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test at enrollment; FCBP must either commit to abstinence from heterosexual intercourse or commit to the use of 2 acceptable methods of birth control; a FCBP is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
- Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy
- All subjects must have given signed, informed consent prior to registration on study
Who cannot join
- Active malignancy requiring therapy such as radiation, chemotherapy, or immunotherapy; exceptions to this are as follows: localized nonmelanotic skin cancer and any cancer that in the judgment of the investigator has been treated with curative intent and will not interfere with the study treatment plan and response assessment
- Known central nervous system (CNS) involvement
- Prior stem cell transplantation (autologous or allogeneic)
- Persistent diarrhea or malabsorption > National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade 2, despite medical management
- Subjects with known immunodeficiency, known autoimmune disease, or concurrent use of immunomodulatory agents
- Any cancer directed therapies between completion of induction chemotherapy and treatment on protocol
Show all 12Show fewer
- Known hypersensitivity to murine or chimeric antibodies or proteins
- Presence of co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens; this includes, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Subjects with known human immunodeficiency virus (HIV) infection
- Subjects with known active hepatitis B virus (HBV) and hepatitis C virus (HCV) infection
- Women must not be pregnant or breast-feeding
- Unwillingness or inability to comply with the protocol
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Georgia Regents University Medical Center
Augusta, Georgia, 30912
Northwestern University
Chicago, Illinois, 60611
About this study
Official title: Phase II Study of Pidilizumab (MDV9300) in Patients With Diffuse Large B-Cell Lymphoma Following First Remission
The purpose of this study is to evaluate pidilizumab and its effect, bad and/or good, on the immune system in relation to its ability to fight cancer cells. Many cancers can be brought to a phase called complete remission (no cancer is found) but have a chance that they may come back. Researchers are working to improve therapy and to find new drugs that lower the chance of disease coming back. This study uses a drug called pidilizumab. The drug targets our immune system. It can change how our immune system finds cancer cells. The drug may kill any remaining cancer cells that we cannot see with computed tomography (CT) scans. The drug, pidilizumab, is being studied in other cancers.
Read the detailed description
PRIMARY OBJECTIVES:
- To estimate the rate of response, whereby either cluster of differentiation (CD)4+CD25+programmed death 1 ligand 1 (PD-L1)+ T lymphocytes or CD4+CD62L+CD127+ T lymphocytes has an "increase" following administration of pidilizumab in patients with diffuse large B-cell lymphoma (DLBCL) that have completed induction chemotherapy.
SECONDARY OBJECTIVES:
- To determine the toxicity and tolerability of pidilizumab therapy following induction chemotherapy.
II. To estimate the progression free survival (PFS) at 2 years. III. To estimate the overall survival (OS) at 2 years. IV. To estimate time to second line chemotherapy (TSLC) at 2 years.
TERTIARY OBJECTIVES:
- To characterize programmed death 1 (PD-1) pathway specific expression markers from the diagnostic biopsy specimens.
II. To characterize serum biomarkers of immune and inflammatory response during treatment with pidilizumab.
III. To characterize levels of soluble PD-L1 related to treatment with pidilizumab.
OUTLINE:
Patients receive pidilizumab intravenously (IV) over approximately 5 hours on day 1. Treatment repeats every 42 days for 3 courses in the absence of disease progression or unacceptable toxicity.
After completion of treatment, patients are followed up at 30 days and then every 3 months for 2 years.
- Being tested
- Laboratory Biomarker Analysis, Pidilizumab
- 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.
Laboratory Biomarker AnalysisOther
Correlative studies
PidilizumabBiological
Also called CT-011
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (pidilizumab) | Experimental | Patients receive pidilizumab IV over approximately 5 hours on day 1. Treatment repeats every 42 days for 3 courses in the absence of disease progression or unacceptable toxicity. Receives: Other: Laboratory Biomarker Analysis; Biological: Pidilizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response to Pidilizumab
Response will be defined as the proportion of CD4+CD25+PD-L1+ T lymphocytes and CD4+CD62L+CD127+ T lymphocytes responders. Responders are defined as either a) a 50% increase or b) a half standard deviation increase in lymphocyte subsets. Lymphocyte subsets will be evaluated by flow cytometry on peripheral blood obtained at specified time points through the treatment period.
Measured: Baseline to up to 127 days. Study terminated before this timeframe. As a result insufficient data was collected to be analyzed.
Secondary outcomes (5)
The Frequency and Severity of Toxicity - Number of Grade 1, 2, 3, 4, and 5, Adverse Events Experienced During Treatment of Pidilizumab Defined by NCI CTCAE v 4.03.
Adverse events (AEs) were graded according to the National Cancer Institute's Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0. In general, AEs are graded according to the following:
Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE
Measured: Start of treatment, and at days 22, 43, 85, 127 and every 3 months for up to 2 years. Due to early termination of the study, AEs for all patients were collected throughout treatment and up to the point of termination of the study.
Overall Survival (OS)
To estimate the overall survival (OS) at 2 years
Measured: From study enrollment until death, or until last contact, assessed up to 2 years. Study terminated before this timeframe. As a result insufficient data was collected to be analyzed.
Progression Free Survival (PFS)
To estimate the progression free survival (PFS) at 2 years. PFS will be defined as time from study enrollment until the first occurrence of disease relapse, progression, re-initiation of cytotoxic chemotherapy, or death due to disease, or until last contact if the patient did not experience any of these.
Measured: Up to 2 years. Study terminated before this timeframe. As a result insufficient data was collected to be analyzed.
Relapsed Disease
Measured: Up to 2 years. Study terminated before this timeframe. As a result insufficient data was collected to be analyzed.
Time to Second Line Chemotherapy (TSLC)
To estimate time to second line chemotherapy (TSLC) at 2 years
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2015 (estimated)
- Study startSep 2015
- Primary completionJan 2017
- Study completionJan 2017
Why it stopped: sponsor decided to discontinue development of the study drug.
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.
- Other trials for Stage III Diffuse Large B-Cell LymphomaStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe 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
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- Gateway for Cancer Research, National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Jane N. Winter, Northwestern University
- Investigators
- Jane Winter, MD, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02530125
- Sponsor's protocol ID
- NU 15H08
- Other IDs
- NCI-2015-01415, STU00200695, NU 15H08, P30CA060553
- Status last verified
- Apr 2017
- First submitted
- 19 Aug 2015
- Last updated
- 19 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Pidilizumab (MDV9300) in Patients With Diffuse Large B-Cell Lymphoma Following First Remission
- ClinicalTrials.gov ID
- NCT02530125
- Acronym / sponsor ID
- NU 15H08
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: sponsor decided to discontinue development of the study drug.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- Gateway for Cancer Research, National Cancer Institute (NCI)
- Study start
- Sep 2015 (actual)
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 20 Aug 2015 (estimated)
- Results
- Posted 19 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate pidilizumab and its effect, bad and/or good, on the immune system in relation to its ability to fight cancer cells. Many cancers can be brought to a phase called complete remission (no cancer is found) but have a chance that they may come back. Researchers are working to improve therapy and to find new drugs that lower the chance of disease coming back. This study uses a drug called pidilizumab. The drug targets our immune system. It can change how our immune system finds cancer cells. The drug may kill any remaining cancer cells that we cannot see with computed tomography (CT) scans. The drug, pidilizumab, is being studied in other cancers.
Detailed description
PRIMARY OBJECTIVES:
- To estimate the rate of response, whereby either cluster of differentiation (CD)4+CD25+programmed death 1 ligand 1 (PD-L1)+ T lymphocytes or CD4+CD62L+CD127+ T lymphocytes has an "increase" following administration of pidilizumab in patients with diffuse large B-cell lymphoma (DLBCL) that have completed induction chemotherapy.
SECONDARY OBJECTIVES:
- To determine the toxicity and tolerability of pidilizumab therapy following induction chemotherapy.
II. To estimate the progression free survival (PFS) at 2 years. III. To estimate the overall survival (OS) at 2 years. IV. To estimate time to second line chemotherapy (TSLC) at 2 years.
TERTIARY OBJECTIVES:
- To characterize programmed death 1 (PD-1) pathway specific expression markers from the diagnostic biopsy specimens.
II. To characterize serum biomarkers of immune and inflammatory response during treatment with pidilizumab.
III. To characterize levels of soluble PD-L1 related to treatment with pidilizumab.
OUTLINE:
Patients receive pidilizumab intravenously (IV) over approximately 5 hours on day 1. Treatment repeats every 42 days for 3 courses in the absence of disease progression or unacceptable toxicity.
After completion of treatment, patients are followed up at 30 days and then every 3 months for 2 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 (pidilizumab) | Experimental | Other: Laboratory Biomarker Analysis, Biological: PidilizumabPatients receive pidilizumab IV over approximately 5 hours on day 1. Treatment repeats every 42 days for 3 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 (18 listed)
- Histologically confirmed de novo DLBCL by the 4th edition of the World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues published in 2008; patients with transform lymphoma are excluded; patients with known primary mediastinal large B-cell lymphoma (PMLBCL) are excluded; patients with known c-v-myc avian myelocytomatosis viral oncogene homolog (c-myc) translocation (by fluorescence in situ hybridization) positive DLBCL are eligible for enrollment; c-myc testing prior to study enrollment is not required; availability of diagnostic biopsy samples in encouraged for the exploratory analysis but not required for enrollment; patients with "double-hit" or "triple-hit" lymphoma are eligible for enrollment
- Previously completed anthracycline-based induction chemotherapy with standard regimens including rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP), dose adjusted (DA)-etoposide, prednisone, vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide (EPOCH), and rituximab (R), and R-hyper cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, methotrexate, and cytarabine (CVAD); patients need a minimum of 6 cycles of treatment; initial treatment with pidilizumab must be administered between 30-90 days from last dose of induction chemotherapy
- Complete remission (CR) according to the Revised Response Criteria for Malignant Lymphoma after first-line treatment
- Stage III/IV disease by Ann Arbor Staging
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Key exclusion criteria (12 listed)
- Active malignancy requiring therapy such as radiation, chemotherapy, or immunotherapy; exceptions to this are as follows: localized nonmelanotic skin cancer and any cancer that in the judgment of the investigator has been treated with curative intent and will not interfere with the study treatment plan and response assessment
- Known central nervous system (CNS) involvement
- Prior stem cell transplantation (autologous or allogeneic)
- Persistent diarrhea or malabsorption > National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade 2, despite medical management
- Subjects with known immunodeficiency, known autoimmune disease, or concurrent use of immunomodulatory agents
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 |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (pidilizumab) |
| PidilizumabAlso: CT-011Given IV | Biological | Treatment (pidilizumab) |
Primary outcome
Response to Pidilizumab
Time frame: Baseline to up to 127 days. Study terminated before this timeframe. As a result insufficient data was collected to be analyzed.
Response will be defined as the proportion of CD4+CD25+PD-L1+ T lymphocytes and CD4+CD62L+CD127+ T lymphocytes responders. Responders are defined as either a) a 50% increase or b) a half standard deviation increase in lymphocyte subsets. Lymphocyte subsets will be evaluated by flow cytometry on peripheral blood obtained at specified time points through the treatment period.
5 secondary outcomes
The Frequency and Severity of Toxicity - Number of Grade 1, 2, 3, 4, and 5, Adverse Events Experienced During Treatment of Pidilizumab Defined by NCI CTCAE v 4.03.
Time frame: Start of treatment, and at days 22, 43, 85, 127 and every 3 months for up to 2 years. Due to early termination of the study, AEs for all patients were collected throughout treatment and up to the point of termination of the study.
Overall Survival (OS)
Time frame: From study enrollment until death, or until last contact, assessed up to 2 years. Study terminated before this timeframe. As a result insufficient data was collected to be analyzed.
Progression Free Survival (PFS)
Time frame: Up to 2 years. Study terminated before this timeframe. As a result insufficient data was collected to be analyzed.
Relapsed Disease
Time frame: Up to 2 years. Study terminated before this timeframe. As a result insufficient data was collected to be analyzed.
Time to Second Line Chemotherapy (TSLC)
Time frame: Up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Stage III Diffuse Large B-Cell Lymphoma
Active, not recruitingPhase 2
Rituximab and Combination Chemotherapy With or Without Lenalidomide in Treating Patients With Newly Diagnosed Stage II-IV Diffuse Large B Cell Lymphoma
Ann Arbor Stage II Diffuse Large B-Cell Lymphoma, Ann Arbor Stage III Diffuse Large B-Cell Lymphoma
Active, not recruitingPhase 2/3
Testing the Addition of a New Anti-cancer Drug, Venetoclax, to Usual Chemotherapy for High Grade B-cell Lymphomas
Diffuse Large B-Cell Lymphoma, Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
Active, not recruitingPhase 1/2
Selinexor Plus Combination Chemotherapy in Treating Patients With Advanced B Cell Non-Hodgkin Lymphoma
Diffuse Large B-Cell Lymphoma, Recurrent B-Cell Non-Hodgkin Lymphoma
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 recruitingPhase 1/2
Vorinostat, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma
Ann Arbor Stage II Non-Hodgkin Lymphoma, Ann Arbor Stage III Non-Hodgkin Lymphoma
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.
Jane Winter, MD principal investigator
Northwestern University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Laboratory Biomarker Analysis and Pidilizumab in people with Stage III Diffuse Large B-Cell Lymphoma and Stage IV Diffuse Large B-Cell Lymphoma, run by Northwestern University at 2 sites 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 18 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: stopped early, as of the sponsor's last update on 19 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 Mar 2018). 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?
Response to Pidilizumab (time frame: Baseline to up to 127 days. Study terminated before this timeframe. As a result insufficient data was collected to be analyzed.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Mar 2018.