Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic LeukemiaPhase 1/2NCT01475058
CD19 CAR T Cells for B Cell Malignancies After Allogeneic Transplant
A Phase 1/2 study testing allogeneic cytomegalovirus-specific cytotoxic T lymphocytes in people with Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia and Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia, run by Fred Hutchinson Cancer Center at 1 site in United States.
Trial summary
This phase I/II trial studies the safety and toxicity of post-transplant treatment with donor T cells engineered to express a chimeric antigen receptor (CAR) targeting CD19 in patients who have had a matched related allogeneic hematopoietic stem cell transplant for a CD19+ B cell malignancy. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia, Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia, Recurrent Adult Acute Lymphoblastic Leukemia
- What is being tested?
- allogeneic cytomegalovirus-specific cytotoxic T lymphocytes
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2012to Jul 2014
- Phase
- Phase 1/2
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with CD19+ B cell malignancy who have persistent, relapsed or progressive disease after hematopoietic stem cell transplant from an human leukocyte antigen (HLA)-matched related donor OR patients with CD19+ B cell malignancy who are planned for or have had a hematopoietic stem cell transplant from an HLA-matched related donor and are at risk of relapse after HCT defined by any one of the disease-specific criteria listed below:
- Philadelphia chromosome negative acute lymphoblastic leukemia:
- Beyond first complete remission (CR) at the time of pre-transplant evaluation
- Required > 1 cycle of induction chemotherapy to achieve CR
- First morphologic CR but with evidence of minimal residual disease by flow cytometry, conventional cytogenetics, fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR)
- First CR with poor risk cytogenetics (t(4:11), t(8;14), hypodiploidy, near triploidy or > 5 cytogenetic abnormalities) at diagnosis
Show all 31Show fewer
- Planned for or have had a reduced intensity conditioned or non-myeloablative transplant
- Philadelphia positive acute lymphoblastic leukemia
- Not in CR at the time of pre-transplant evaluation
- In CR with the following features:
- Intolerant or unwilling to use a TKI after HCT
- Current or previous detection of cytogenetic abnormalities in addition to t(9;22) by conventional karyotyping, FISH or molecular methods
- Chronic lymphocytic leukemia, or low grade B cell lymphomas:
- Failed or ineligible for prior immunochemotherapy that included a purine analog and anti-CD20 monoclonal antibody AND a lymph node >= 5 cm at the time of pre-transplant evaluation
- Mantle cell lymphoma:
- Failed or ineligible for autologous transplant AND a lymph node >= 2 cm at the time of pre-transplant evaluation
- Diffuse large B cell lymphomas, large B cell transformation of an indolent lymphoma or other aggressive B cell lymphomas
- Failed or ineligible for autologous transplant AND not in CR at the time of pre-transplant evaluation
- Confirmation of tumor diagnosis and expression of CD19 after review by University of Washington Medical Center (UWMC) or Seattle Cancer Care Alliance (SCCA) pathology services
- The patient has signed the informed consent form for this study
- DONOR: Genotypic or phenotypic HLA-identical family members
- DONOR: Express one or more of the following combinations of viral serostatus and HLA allele:
- CMV seropositive and HLA-A*0101 positive
- CMV seropositive and HLA-A*0201 positive
- CMV seropositive and HLA-B*0702 positive
- CMV seropositive and HLA-B*0801 positive
- EBV seropositive and HLA-A*0201 positive
- EBV seropositive and HLA-B*0801 positive
- DONOR: Hematocrit >= 35% at enrollment
- DONOR: Age >= 18 years
- DONOR: The donor has signed the informed consent form for the study
Who cannot join
- Known central nervous system (CNS) tumor (CNS2 or CNS3) that is refractory to intrathecal chemotherapy and/or cranio-spinal radiation; patients with a history of CNS disease that has been effectively treated to CNS1 or lower evidence of disease will be eligible
- Human immunodeficiency virus (HIV) seropositive
- Significant medical or psychological conditions that would make them unsuitable candidates for T cell therapy
- Fertile patients unwilling to use contraception during and for 12 months after protocol enrollment
- Pregnant or breast-feeding
- DONOR: G-CSF administered within one month prior to the blood draw for T cell collection
Show all 20Show fewer
- DONOR: Unable for any reason to provide a 400 ml blood draw
- DONOR: Inadequate peripheral veins for blood collection
- DONOR: HIV-1, HIV-2, human T-lymphotropic virus (HTLV)-1 or HTLV-2 seropositive
- DONOR: Active hepatitis B or hepatitis C virus infection
- DONOR: Positive serologic test for syphilis
- DONOR: Aberrant CD45RA isoform expression on all T cells
- DONOR: Systolic blood pressure (BP) < 80 or > 200
- DONOR: Heart rate < 50 or > 120, if considered due to cardiac disease
- DONOR: Oxygen (O2) saturation < 88% on room air
- DONOR: Serum creatinine (Cr) > 3.0
- DONOR: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 4 x the upper limit of normal
- DONOR: Unable to provide informed consent to participate
- DONOR: Significant medical conditions (e.g. immunosuppressive therapy) that would make them unsuitable T cell donors
- DONOR: Pregnant or nursing
Trial locations and contacts
1 site in 1 country.
United States1 site
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
Official title: A Phase I/II Study of Cellular Immunotherapy With Donor Central Memory-derived Virus-specific CD8+ T-cells Engineered to Target CD19 for CD19+ Malignancies After Allogeneic Hematopoietic Stem Cell Transplant
This phase I/II trial studies the safety and toxicity of post-transplant treatment with donor T cells engineered to express a chimeric antigen receptor (CAR) targeting CD19 in patients who have had a matched related allogeneic hematopoietic stem cell transplant for a CD19+ B cell malignancy.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the safety and feasibility of pre-emptive adoptive T cell therapy using ex vivo expanded cytomegalovirus (CMV)- or Epstein-Barr virus (EBV)-specific T cells derived from donor CD62L+ central memory (TCM) cells and genetically modified to express a CD19-specific chimeric antigen receptor (CAR) in patients in complete remission after human leukocyte antigen (HLA)-matched related donor hematopoietic stem cell transplantation (HCT) for CD19+ B cell malignancies at high risk of post-HCT relapse. (Cohort A)
II. To assess the safety and feasibility of adoptive T cell therapy using ex vivo expanded CMV- or EBV-specific T cells derived from donor CD62L+ TCM cells and genetically modified to express a CD19-specific CAR in patients with persistent, progressive or relapsed disease after HLA-matched related donor HCT for CD19+ B cell malignancies. (Cohort B)
SECONDARY OBJECTIVES:
- To determine the duration of in vivo persistence of adoptively transferred bi-specific CD8+ T cells, and the phenotype of persisting T cells.
II. To determine if adoptively transferred bi-specific CD8+ T cells traffic to the bone marrow and function in vivo.
III. To determine if adoptively transferred bi-specific CD8+ T cells proliferate in allogeneic HCT recipients that reactivate CMV or EBV.
IV. To determine if the adoptive transfer of bi-specific CD8+ T cells eliminates CD19+ tumor cells in the subset of patients with a measurable tumor burden prior to T cell transfer.
OUTLINE:
At least 30 days after HCT, patients will receive one intravenous (IV) infusion of CMV/CD19 or EBV/CD19 bi-specific CD8+ T cells.
After completion of study treatment, patients are followed up periodically for 15 years.
- Conditions
- Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia, Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Mantle Cell Lymphoma
- Being tested
- allogeneic cytomegalovirus-specific cytotoxic T lymphocytes
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Large-Cell, Immunoblastic, Lymphoma, Mantle-Cell, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
allogeneic cytomegalovirus-specific cytotoxic T lymphocytesBiological
Also called allogeneic CMV-specific CTLs
Allogeneic CD19-specific chimeric antigen receptor-modified CD8+ central memory derived virus-specific T cells. Allogeneic CD19CAR-TCM cells given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (T cell therapy) | Experimental | Patients undergo one IV infusion of donor-derived CD8+ central memory-derived CMV/CD19 or EBV/CD19 bi-specific T cells, at least 30 days after HCT. Receives: Biological: allogeneic cytomegalovirus-specific cytotoxic T lymphocytes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and toxicity assessment of study treatment
Incidence of grade >= 3 toxicity, as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 occurring from the T cell infusion through day 42 after the T cell infusion. Analysis will be performed separately in patients in complete remission (cohort A) or with detectable disease (cohort B) at day 28 post-transplant (prior to the T cell infusion). Incidence of acute GVHD occurring from the T cell infusion through day 42 after the T cell infusion will be assessed.
Measured: Up to day 42 after the T cell infusion
Feasibility assessment of study treatment
If the prescribed T cell dose is delivered in more than 50% of the patients, this approach will be considered feasible for further study to reduce relapse after allogeneic HCT.
Measured: Up to 5 years
Secondary outcomes (1)
Anti-tumor efficacy and duration of persistence, migration, and function of adoptively transferred bi-specific effector cells
Measured: Up to 15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2011 (estimated)
- Study startApr 2012
- Primary completionApr 2014
- Study completionJul 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by Fred Hutchinson Cancer CenterThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Cameron Turtle, Fred Hutchinson Cancer Center
- Investigators
- Cameron Turtle, Principal investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01475058
- Sponsor's protocol ID
- 2494.00
- Other IDs
- NCI-2011-01819, 2494.00, P30CA015704, R01CA136551
- Status last verified
- Feb 2017
- First submitted
- 10 Nov 2011
- Last updated
- 15 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
PubMed 34515338
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of Cellular Immunotherapy With Donor Central Memory-derived Virus-specific CD8+ T-cells Engineered to Target CD19 for CD19+ Malignancies After Allogeneic Hematopoietic Stem Cell Transplant
- ClinicalTrials.gov ID
- NCT01475058
- Acronym / sponsor ID
- 2494.00
- Conditions
- Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia, Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Mantle Cell Lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Fred Hutchinson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Apr 2012
- Primary completion
- Apr 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 21 Nov 2011 (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.
This phase I/II trial studies the safety and toxicity of post-transplant treatment with donor T cells engineered to express a chimeric antigen receptor (CAR) targeting CD19 in patients who have had a matched related allogeneic hematopoietic stem cell transplant for a CD19+ B cell malignancy.
Detailed description
PRIMARY OBJECTIVES:
- To assess the safety and feasibility of pre-emptive adoptive T cell therapy using ex vivo expanded cytomegalovirus (CMV)- or Epstein-Barr virus (EBV)-specific T cells derived from donor CD62L+ central memory (TCM) cells and genetically modified to express a CD19-specific chimeric antigen receptor (CAR) in patients in complete remission after human leukocyte antigen (HLA)-matched related donor hematopoietic stem cell transplantation (HCT) for CD19+ B cell malignancies at high risk of post-HCT relapse. (Cohort A)
II. To assess the safety and feasibility of adoptive T cell therapy using ex vivo expanded CMV- or EBV-specific T cells derived from donor CD62L+ TCM cells and genetically modified to express a CD19-specific CAR in patients with persistent, progressive or relapsed disease after HLA-matched related donor HCT for CD19+ B cell malignancies. (Cohort B)
SECONDARY OBJECTIVES:
- To determine the duration of in vivo persistence of adoptively transferred bi-specific CD8+ T cells, and the phenotype of persisting T cells.
II. To determine if adoptively transferred bi-specific CD8+ T cells traffic to the bone marrow and function in vivo.
III. To determine if adoptively transferred bi-specific CD8+ T cells proliferate in allogeneic HCT recipients that reactivate CMV or EBV.
IV. To determine if the adoptive transfer of bi-specific CD8+ T cells eliminates CD19+ tumor cells in the subset of patients with a measurable tumor burden prior to T cell transfer.
OUTLINE:
At least 30 days after HCT, patients will receive one intravenous (IV) infusion of CMV/CD19 or EBV/CD19 bi-specific CD8+ T cells.
After completion of study treatment, patients are followed up periodically for 15 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 (T cell therapy) | Experimental | Biological: allogeneic cytomegalovirus-specific cytotoxic T lymphocytesPatients undergo one IV infusion of donor-derived CD8+ central memory-derived CMV/CD19 or EBV/CD19 bi-specific T cells, at least 30 days after HCT. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Patients with CD19+ B cell malignancy who have persistent, relapsed or progressive disease after hematopoietic stem cell transplant from an human leukocyte antigen (HLA)-matched related donor OR patients with CD19+ B cell malignancy who are planned for or have had a hematopoietic stem cell transplant from an HLA-matched related donor and are at risk of relapse after HCT defined by any one of the disease-specific criteria listed below:
- Confirmation of tumor diagnosis and expression of CD19 after review by University of Washington Medical Center (UWMC) or Seattle Cancer Care Alliance (SCCA) pathology services
- The patient has signed the informed consent form for this study
- DONOR: Genotypic or phenotypic HLA-identical family members
- DONOR: Express one or more of the following combinations of viral serostatus and HLA allele:
Key exclusion criteria (20 listed)
- Known central nervous system (CNS) tumor (CNS2 or CNS3) that is refractory to intrathecal chemotherapy and/or cranio-spinal radiation; patients with a history of CNS disease that has been effectively treated to CNS1 or lower evidence of disease will be eligible
- Human immunodeficiency virus (HIV) seropositive
- Significant medical or psychological conditions that would make them unsuitable candidates for T cell therapy
- Fertile patients unwilling to use contraception during and for 12 months after protocol enrollment
- Pregnant or breast-feeding
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 |
|---|---|---|
| allogeneic cytomegalovirus-specific cytotoxic T lymphocytesAlso: allogeneic CMV-specific CTLsAllogeneic CD19-specific chimeric antigen receptor-modified CD8+ central memory derived virus-specific T cells. Allogeneic CD19CAR-TCM cells given IV | Biological | Treatment (T cell therapy) |
Primary outcome
Safety and toxicity assessment of study treatment
Time frame: Up to day 42 after the T cell infusion
Incidence of grade >= 3 toxicity, as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 occurring from the T cell infusion through day 42 after the T cell infusion. Analysis will be performed separately in patients in complete remission (cohort A) or with detectable disease (cohort B) at day 28 post-transplant (prior to the T cell infusion). Incidence of acute GVHD occurring from the T cell infusion through day 42 after the T cell infusion will be assessed.
Feasibility assessment of study treatment
Time frame: Up to 5 years
If the prescribed T cell dose is delivered in more than 50% of the patients, this approach will be considered feasible for further study to reduce relapse after allogeneic HCT.
1 secondary outcome
Anti-tumor efficacy and duration of persistence, migration, and function of adoptively transferred bi-specific effector cells
Time frame: Up to 15 years
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 15 Feb 2017.
- Derived from this study: PubMed 34515338Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
Related trials for Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia
Active, not recruitingPhase 2
Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia
Acute Lymphoblastic Leukemia, Adult B Acute Lymphoblastic Leukemia
RecruitingPhase 1/2
Safety and Efficacy of Asciminib in Pediatrics and Young Adults With Relapse/Refractory (r/r) Philadelphia Positive (Ph+) or ABL-class Ph-like Acute Lymphoblastic Leukemia (ALL)
Acute Lymphoblastic Leukemia, Leukemia, Lymphoblastic, Acute, Philadelphia-Positive
RecruitingPhase 2
Asparaginase Erwinia Chrysanthemi With Chemotherapy for the Treatment of High-Risk Adults With Newly Diagnosed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative, Lymphoblastic Lymphoma
Active, not recruitingPhase 2
Combination Chemotherapy and Ponatinib Hydrochloride in Treating Patients With Acute Lymphoblastic Leukemia
Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Acute Lymphoblastic Leukemia
Enrolling by invitationPhase 2
Adding Asciminib to Usual Treatment for Adults With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Acute Lymphoblastic Leukemia
Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia, CD19+ Acute Leukemia
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.
Cameron Turtle principal investigator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing allogeneic cytomegalovirus-specific cytotoxic T lymphocytes in people with Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia and Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia, run by Fred Hutchinson Cancer Center 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 31 inclusion and 20 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 15 Feb 2017. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
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?
Safety and toxicity assessment of study treatment (time frame: Up to day 42 after the T cell infusion). 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 NCT01475058, 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 15 Feb 2017.