Latest finding for treating newly diagnosed Hodgkin lymphoma

A Phase I study of brentuximab vedotin in patients with newly diagnosed Hodgkin lymphoma was led by UNC Lineberger Comprehensive Cancer Center, British Columbia Cancer Agency, Mayo Clinic, and MD Anderson - an interim report was presented at the ASH annual meeting in December 2011.

 

The study recommended that brentuximab vedotin should not be combined with the standard ABVD chemotherapy regimen due to increased risk of pulmonary toxicity but found that the safety and efficacy of this therapy combined with AVD to be encouraging.

 

UNC Lineberger plans to lead a Phase II clinical trial using brentuximab vedotin for patients with early stage Hodgkin lymphoma in collaboration with Mayo Clinic and the UNC Cancer Network.

 

For more information about this trial, check for updates at clinicaltrials.gov or contact Dr. Steven Park at 919-843-7942.

 

Overcoming Bortezomib Resistance in Multiple Myeloma

 

Dr. Peter Voorhees is seeking to identify novel therapeutics that overcome resistance to proteasome inhibitors for patients with multiple myeloma. Preclinical data he previously generated revealed a role for interleukin-6, a cytokine involved in myeloma cell growth and survival, in resistance to the proteasome inhibitor bortezomib. These data paved the way for a Phase II clinical trial evaluating the combination of bortezomib and siltuximab, a monoclonal antibody that inhibits the function of interleukin-6, for patients with relapsed myeloma.

 

Currently, the UNC Myeloma program is involved in two clinical trials evaluating other pathways to overcome proteasome inhibitor resistance: the aggresome and AKT pathways. To this end, a Phase II study of pegylated liposomal doxorubicin, bortezomib and vorinostat, an inhibitor of histone deacetylase-6 and the aggresome pathway is planned.  An industry-sponsored Phase IB study evaluating the combination of bortezomib, dexamethasone and the AKT inhibitor, GSK2110183, is on-going.

 

Dr. Voorhees is also collaborating with Drs. Nancy Allbritton and Marcey Waters to develop novel fluorescent probes that will have the ability to measure enzyme activity at the level of the single myeloma cell. They are initially developing probes that measure AKT and proteasome activity in myeloma cells, which will eventually be used as pharmacodynamic measures of target inhibition in patient myeloma samples and to better study resistance to inhibitors of these enzymes in myeloma.

 

For more information about current myeloma clinical trials, contact Dr. Peter Voorhees at 919-966-4431.

 

Jonathan Serody, MD, Elizabeth Thomas Professor, Division of Hematology & Oncology, Microbiology & Immunology, talks about clinical trials, recent breakthroughs, understanding cancer genetics and moving forward. Watch video.

 

 

Finding genetic polymorphisms that correlate with response to therapy

Drs. Kristy Richards and Steven Park are working together on a clinical project to study a known polymorphism in a gene, FCGR3A - they have shown that FCGR3A polymorphism affects rituximab response in the most common subtype of lymphoma, diffuse large B-cell lymphoma.

 

Patients with one version of FCGR3A, encoding valine at position 158, have a significantly better overall and progression-free survival than patients with phenylalanine at that position after treatment with R-CHOP (rituximab combined with chemotherapy).  

 

Dr. Richards and Dr. Park are now planning to genotype a larger population of rituximab-treated patients to confirm the results. They are also planning a clinical trial to treat patients who have the less-favorable FCGR3A genotype with such alternative therapies as newer anti-CD20 antibodies or increased-dose rituximab.

 

Dr. Richards’ laboratory group is also using a large-scale genetic screen to identify additional genes with polymorphisms that can affect response to rituximab and to other drugs used to treat lymphoma. 

 

The hope is that discovering these novel genes will reveal more about the mechanism of action of rituximab (and other drugs) as well as to predict which patients are resistant and may respond better to alternative therapies.

 

This course is designed to provide data driven and practical recommendations for coping with the challenges of cancer.

 

The symposium will be held on April 20 & 21, 2012 in Greenville, NC. For more information, including registration and course credit details and a schedule, view this flyer or call 252-744-3546.

 

 

UNC Lineberger    N.C. Cancer Hospital    Clinical Trials     Clinical Programs    Comprehensive Cancer Support

 

For questions about all clinical trials at UNC (including those at UNC that are also offered at other sites), contact the UNC Lineberger protocol office at 919-966-4432 or (toll-free) 1-877-668-0683.

 

To make an appointment at the N.C. Cancer Hospital for one of your patients, visit our web page for referring physicians. You may also contact the Carolina Consultation Center at 1-800-862-6264.