This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Hypothesis:The objectives of this Phase I study with patients with non-Hodgkin's lymphoma (NHL) are:1. To define the safety profile of 4 weekly doses of an anti-human CD40 monoclonal antibody, SGN-402. To determine the maximum tolerated dose of 4 weekly doses of SGN3. To obtain preliminary anti-tumor activity of SGN-40Goals:NHL is a heterogeneous malignancy originating from lymphocytes. In the United States, the incidence is estimated at about 54,000/yr with a prevalence of approximately 331,000. The majority (80%) of lymphoma cases is of B-cell origin. While the disease can occur in all ages, the incidence increases with age, with the usual onset beginning in adults over 40 years. NHL is characterized by a clonal proliferation of lymphocytes that accumulate in the lymph nodes, blood, bone marrow, and spleen, although any major organ may be involved.NHL can be divided into two prognostic groups: indolent and aggressive. Intensive combination chemotherapy regimens cure some cases of the aggressive forms of NHL. The more indolent and follicular forms of the disease that affect nearly half of all patients with NHL are considered incurable. While indolent NHL is responsive to radiation therapy and chemotherapy, a continuous rate of relapse is usually seen in advanced stages. In patients who have relapsed from primary treatment and who are not candidates for stem cell transplantation, novel therapies that can provide clinical benefit are needed.The expression of CD40, a member of the tumor necrosis factor (TNF) superfamily, on aggressive NHL makes this antigen an attractive target for treatment of relapsed patients. CD40 is a receptor molecule on the cell surface of all mature B cells (B lymphocytes), most B-cell malignancies, monocytes, dendritic cells (in the nervous system), endothelial cells (within blood vessels), and epithelial cells.Endpoints:This is a Phase I study, and as such endpoints will include:+ Defining the safety profile [dose limiting toxicity (DLT)] of 4 weekly doses of SGN-40 in patients with NHL+ Determining the maximum tolerated dose (MTD) of 4 weekly doses of SGN-40 in patients with NHL+ Obtaining preliminary anti-tumor activity of SGN-40 in patients with NHL

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000070-46
Application #
7717874
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2007-12-01
Project End
2008-05-31
Budget Start
2007-12-01
Budget End
2008-05-31
Support Year
46
Fiscal Year
2008
Total Cost
$796
Indirect Cost
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Latva-Rasku, Aino; Honka, Miikka-Juhani; Stan?áková, Alena et al. (2018) A Partial Loss-of-Function Variant in AKT2 Is Associated With Reduced Insulin-Mediated Glucose Uptake in Multiple Insulin-Sensitive Tissues: A Genotype-Based Callback Positron Emission Tomography Study. Diabetes 67:334-342
Evangelou, Evangelos (see original citation for additional authors) (2018) Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits. Nat Genet 50:1412-1425
Doherty, Aiden; Smith-Byrne, Karl; Ferreira, Teresa et al. (2018) GWAS identifies 14 loci for device-measured physical activity and sleep duration. Nat Commun 9:5257
Askie, Lisa M; Darlow, Brian A; Finer, Neil et al. (2018) Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration. JAMA 319:2190-2201
Frayling, Timothy M; Beaumont, Robin N; Jones, Samuel E et al. (2018) A Common Allele in FGF21 Associated with Sugar Intake Is Associated with Body Shape, Lower Total Body-Fat Percentage, and Higher Blood Pressure. Cell Rep 23:327-336
Srinivasan, Lakshmi; Page, Grier; Kirpalani, Haresh et al. (2017) Genome-wide association study of sepsis in extremely premature infants. Arch Dis Child Fetal Neonatal Ed 102:F439-F445
Di Fiore, Juliann M; Martin, Richard J; Li, Hong et al. (2017) Patterns of Oxygenation, Mortality, and Growth Status in the Surfactant Positive Pressure and Oxygen Trial Cohort. J Pediatr 186:49-56.e1
Denson, Lee A; McDonald, Scott A; Das, Abhik et al. (2017) Early Elevation in Interleukin-6 is Associated with Reduced Growth in Extremely Low Birth Weight Infants. Am J Perinatol 34:240-247
Holmes, Michael V; Pulit, Sara L; Lindgren, Cecilia M (2017) Genetic and epigenetic studies of adiposity and cardiometabolic disease. Genome Med 9:82
Younge, Noelle; Goldstein, Ricki F; Bann, Carla M et al. (2017) Survival and Neurodevelopmental Outcomes among Periviable Infants. N Engl J Med 376:617-628

Showing the most recent 10 out of 589 publications