|By PR Newswire||
|December 8, 2012 08:00 AM EST||
ATLANTA, Dec. 8, 2012 /PRNewswire-USNewswire/ -- The promising investigational targeted therapy ibrutinib and its mechanism of silencing gene communication pathways critical to the development of cancer may be an effective way to combat chronic lymphocytic leukemia (CLL), according to studies presented today at the 54th Annual Meeting of the American Society of Hematology (ASH).
CLL is a blood cancer that causes abnormal white blood cells called lymphocytes to accumulate in the blood, bone marrow, and in the lymph nodes or other organs, causing these organs to enlarge. Approximately 15,000 Americans are diagnosed with CLL every year; nearly 70 percent of those affected are 65 and older.,  For some patients with slower growing disease, physicians employ "watch and wait" strategies to minimize unnecessary treatment. However, patients with high-risk features such as rapidly progressing disease require prompt treatment to manage symptoms and reduce organ damage.
Ibrutinib is a specialized anti-cancer therapy that targets the Bruton's tyrosine kinase (BTK, an enzyme important in the development of CLL). As an inhibitor of BTK, ibrutinib selectively targets leukemia cells, promoting their death and preventing them from growing while leaving normal cells unharmed. Studies suggest this design allows the drug to more effectively treat the disease, with encouraging early results in harder-to-treat patient groups such as elderly untreated patients and those whose disease has become resistant to other therapies or those who have experienced disease recurrence after receiving other therapies. Two studies will present efficacy and safety results testing the compound alone and in combination with other currently used therapies for CLL.
"The evidence collected to date on ibrutinib demonstrates that it may have the potential to improve long-term prognosis for patients who are not sensitive to standard treatment," said Claire E. Dearden, MD, moderator of the press conference, Consultant Hematologist and Head of the CLL Unit at The Royal Marsden NHS Foundation Trust in London. "Equally important, the exciting efficacy and safety data that we are seeing for this drug in these studies underscore the significant progress we are making in our quest to better understand and attack the specific cellular targets responsible for CLL, particularly in these vulnerable patient populations."
This press conference will take place on Saturday, December 8, at 8:00 a.m. EST.
The Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib (PCI-32765) Promotes High Response Rate, Durable Remissions, and is Tolerable in Treatment Naive (TN) and Relapsed or Refractory (RR) Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Patients including Patients with High-Risk (HR) Disease: New and Updated Results of 116 Patients in Phase Ib/II Study [Abstract 189]
New research demonstrates that a novel investigational therapeutic agent called ibrutinib may be an effective and safe targeted treatment option for previously untreated, hard-to-treat, and relapsed patients with chronic lymphocytic leukemia (CLL).
Primary treatment for CLL includes a combined chemotherapy-based regimen with fludarabine and cyclophosphamide, along with the immune therapy rituximab. While rituximab is effective, it is generally not well tolerated among elderly patients. Treatment with this drug also compromises the immune system by attacking both cancerous and normal cells, putting patients at risk for a range of infections and increasing their risk of developing treatment-related acute myeloid leukemia.
To understand if ibrutinib may be effective for elderly CLL patients and to identify which patients might benefit most from the drug, researchers enrolled 116 CLL patient participants in several treatment cohorts: patients who were never treated (the treatment-naive group), those who had received two or more prior therapies (the relapsed/refractory group), those who had relapsed within two years of treatment (the high-risk group), and those over age 65. Two oral dosing regimens (420 mg or 840 mg daily) of ibrutinib were used. The primary goal of the study was to determine the safety of the low and high doses; secondary objectives included efficacy, measures of the intensity of the drug's effect in the body, and the long-term safety of administering this therapy continuously until relapse.
The study found that response to therapy was high across the cohorts, with largely manageable toxicities. Previously untreated elderly patients responded best to the agent, with 71 percent experiencing a complete or partial response at either treatment dose. The same response was observed in 67 percent of the relapsed patients and 50 percent of the high-risk patient cohort. After 22 months of follow-up, the disease had not progressed in 96 percent of previously untreated patients and 76 percent of relapsed and high-risk patients.
The treatment regimen was generally well-tolerated, as only non-severe side effects were observed, including diarrhea, fatigue, chest infection, rash, nausea, joint pain, and infrequent and transient low blood counts. Investigators found no evidence of cumulative toxicity or long-term safety concerns with a median follow-up of 16 months for treated patients. These results demonstrate ibrutinib's potential as a highly active, well-tolerated first-line therapy for CLL.
"As we learn more about how to target specific essential survival signals and communications pathways in cancer, we are improving our ability to effectively treat the disease while avoiding the toxicities of chemotherapy and potential relapse," said John C. Byrd, MD, lead author and Director of the Division of Hematology at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute in Columbus. "If we can replicate these high survival rates and good tolerability with ibrutinib through larger scale Phase III studies, we may find it to be an extremely valuable new therapy for not just elderly, but for all CLL patients."
Dr. Byrd will present this study in an oral presentation on Sunday, December 9, at 5:00 p.m. EST at the Georgia World Congress Center in Thomas Murphy Ballroom 4, Level 5, Building B.
The BTK Inhibitor Ibrutinib (PCI-32765) in Combination with Rituximab is Well−Tolerated and Displays Profound Activity in High-Risk Chronic Lymphocytic Leukemia (CLL) Patients
The combination of the novel investigational agent ibrutinib with an established therapeutic antibody, rituximab, may present a safer and more effective option than the current standard chemotherapy-based treatment regimen for patients with high-risk CLL.
While current chemotherapy-based treatment options for CLL patients are effective, they come with toxic side effects that are challenging for elderly patients. Physicians have long awaited new options that offer better tolerability. Ibrutinib is designed to selectively target leukemia cell growth, with the aim of effectively treating the disease without the toxicities of chemotherapy. Data from earlier studies of ibrutinib have shown it to be equally effective in both low- and high-risk CLL.
High-risk CLL patients typically have unfavorable responses to standard CLL therapies and a dismal outcome. Such patients are characterized by presence of chromosomal abnormalities (i.e., deletions of chromosome 17p or 11q) or short remissions (less than 3 years) after standard chemo-immunotherapy. To develop an alternative therapy regimen for this patient population, researchers explored the combination of ibrutinib and the anti-CD20 antibody rituximab in high-risk CLL.
In this Phase II study conducted at The University of Texas MD Anderson Cancer Center in Houston, ibrutinib was given in combination with rituximab to evaluate its potential to accelerate and improve CLL patient responses. Forty patients were treated with 420 mg of ibrutinib daily in combination with weekly rituximab for four weeks, followed by ibrutinib daily plus monthly rituximab until month six, followed by single-agent ibrutinib.
Positive responses to therapy were shown among the vast majority of treated patients. At four months of follow-up, the overall response rate was 85 percent and almost all (38 of 40) patients continued on therapy without disease progression. Of the 20 patients evaluable for early response, 17 achieved a partial remission. Patient health questionnaires also noted improvements in health and the quality of life of all treated patients.
Overall, the regimen was well-tolerated among participants, with little severe toxicity that was largely unrelated and short in duration. After treatment with ibrutinib-rituximab (iR) combination therapy, most cases of early lymphocytosis (increase in white blood cells that is a sign of infection), due to the ibrutinib-induced shift of CLL cells from lymph node tissues into the blood, peaked early and resolved; at four months of follow-up, only three treated patients had lymphocytosis that had not yet resolved. This shorter lymphocytosis duration, when compared to single-agent use of ibrutinib, is presumably related to the addition of rituximab.
"We know that high-risk CLL patients struggle with the effects of standard chemo-immunotherapy and eventually become resistant. For these harder-to-treat patients, ibrutinib in combination with rituximab appears to be a safer option with high efficacy and without the related risks," said Jan Burger, MD, PhD, lead author and Associate Professor of Medicine in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston. "Based on these promising results, we need larger-scale studies of ibrutinib-rituximab in high-risk CLL, with the goal of accelerating the development of this therapy for patients who most urgently need better options."
Dr. Burger will present this study in an oral presentation on Sunday, December 9, at 4:30 p.m. EST at the Georgia World Congress Center in Thomas Murphy Ballroom 4, Level 5, Building B.
American Society of Hematology 54th Annual Meeting
The study authors and moderator will be available for interviews after the press conference or by telephone. Additional press briefings will take place throughout the meeting on efforts to reduce toxicity and improve survival for blood cancer therapy, strategies to increase the efficacy and safety of treatments for bleeding and clotting disorders, new targeted treatment for hard-to-treat blood disorders, and advances in stem cell technology and transplant strategies. For the complete annual meeting program and abstracts, visit www.hematology.org/2012abstracts. Follow ASH (@ASH_hematology) on Twitter (use the hashtag #ASH12 when posting tweets about the meeting) and on Facebook at www.facebook.com/AmericanSocietyofHematology for the most up-to-date information about the 2012 ASH Annual Meeting.
The American Society of Hematology (ASH) (www.hematology.org) is the world's largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 50 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. The official journal of ASH is Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field, which is available weekly in print and online.
 National Cancer Institute, "SEER Stat Fact Sheets: Chronic Lymphocytic Leukemia," http://seer.cancer.gov/statfacts/html/clyl.html (Accessed October 2012).
 Gribben, J.G., "How I treat CLL up front," Blood 115, no. 2 (2009): 187-197.
SOURCE American Society of Hematology
We are reaching the end of the beginning with WebRTC, and real systems using this technology have begun to appear. One challenge that faces every WebRTC deployment (in some form or another) is identity management. For example, if you have an existing service – possibly built on a variety of different PaaS/SaaS offerings – and you want to add real-time communications you are faced with a challenge relating to user management, authentication, authorization, and validation. Service providers will want to use their existing identities, but these will have credentials already that are (hopefully) i...
Nov. 26, 2014 03:00 PM EST Reads: 805
The Internet of Things will greatly expand the opportunities for data collection and new business models driven off of that data. In her session at @ThingsExpo, Esmeralda Swartz, CMO of MetraTech, discussed how for this to be effective you not only need to have infrastructure and operational models capable of utilizing this new phenomenon, but increasingly service providers will need to convince a skeptical public to participate. Get ready to show them the money!
Nov. 26, 2014 03:00 PM EST Reads: 801
The Internet of Things will put IT to its ultimate test by creating infinite new opportunities to digitize products and services, generate and analyze new data to improve customer satisfaction, and discover new ways to gain a competitive advantage across nearly every industry. In order to help corporate business units to capitalize on the rapidly evolving IoT opportunities, IT must stand up to a new set of challenges. In his session at @ThingsExpo, Jeff Kaplan, Managing Director of THINKstrategies, will examine why IT must finally fulfill its role in support of its SBUs or face a new round of...
Nov. 26, 2014 03:00 PM EST Reads: 662
Cultural, regulatory, environmental, political and economic (CREPE) conditions over the past decade are creating cross-industry solution spaces that require processes and technologies from both the Internet of Things (IoT), and Data Management and Analytics (DMA). These solution spaces are evolving into Sensor Analytics Ecosystems (SAE) that represent significant new opportunities for organizations of all types. Public Utilities throughout the world, providing electricity, natural gas and water, are pursuing SmartGrid initiatives that represent one of the more mature examples of SAE. We have s...
Nov. 26, 2014 03:00 PM EST Reads: 710
One of the biggest challenges when developing connected devices is identifying user value and delivering it through successful user experiences. In his session at Internet of @ThingsExpo, Mike Kuniavsky, Principal Scientist, Innovation Services at PARC, described an IoT-specific approach to user experience design that combines approaches from interaction design, industrial design and service design to create experiences that go beyond simple connected gadgets to create lasting, multi-device experiences grounded in people's real needs and desires.
Nov. 26, 2014 02:45 PM EST Reads: 809
"Matrix is an ambitious open standard and implementation that's set up to break down the fragmentation problems that exist in IP messaging and VoIP communication," explained John Woolf, Technical Evangelist at Matrix, in this SYS-CON.tv interview at @ThingsExpo, held Nov 4–6, 2014, at the Santa Clara Convention Center in Santa Clara, CA.
Nov. 26, 2014 02:45 PM EST Reads: 648
Connected devices and the Internet of Things are getting significant momentum in 2014. In his session at Internet of @ThingsExpo, Jim Hunter, Chief Scientist & Technology Evangelist at Greenwave Systems, examined three key elements that together will drive mass adoption of the IoT before the end of 2015. The first element is the recent advent of robust open source protocols (like AllJoyn and WebRTC) that facilitate M2M communication. The second is broad availability of flexible, cost-effective storage designed to handle the massive surge in back-end data in a world where timely analytics is e...
Nov. 26, 2014 02:15 PM EST Reads: 535
P2P RTC will impact the landscape of communications, shifting from traditional telephony style communications models to OTT (Over-The-Top) cloud assisted & PaaS (Platform as a Service) communication services. The P2P shift will impact many areas of our lives, from mobile communication, human interactive web services, RTC and telephony infrastructure, user federation, security and privacy implications, business costs, and scalability. In his session at @ThingsExpo, Robin Raymond, Chief Architect at Hookflash, will walk through the shifting landscape of traditional telephone and voice services ...
Nov. 26, 2014 02:00 PM EST Reads: 1,405
Scott Jenson leads a project called The Physical Web within the Chrome team at Google. Project members are working to take the scalability and openness of the web and use it to talk to the exponentially exploding range of smart devices. Nearly every company today working on the IoT comes up with the same basic solution: use my server and you'll be fine. But if we really believe there will be trillions of these devices, that just can't scale. We need a system that is open a scalable and by using the URL as a basic building block, we open this up and get the same resilience that the web enjoys.
Nov. 25, 2014 09:30 PM EST Reads: 1,160
The Internet of Things is tied together with a thin strand that is known as time. Coincidentally, at the core of nearly all data analytics is a timestamp. When working with time series data there are a few core principles that everyone should consider, especially across datasets where time is the common boundary. In his session at Internet of @ThingsExpo, Jim Scott, Director of Enterprise Strategy & Architecture at MapR Technologies, discussed single-value, geo-spatial, and log time series data. By focusing on enterprise applications and the data center, he will use OpenTSDB as an example t...
Nov. 25, 2014 09:30 PM EST Reads: 1,209
The Domain Name Service (DNS) is one of the most important components in networking infrastructure, enabling users and services to access applications by translating URLs (names) into IP addresses (numbers). Because every icon and URL and all embedded content on a website requires a DNS lookup loading complex sites necessitates hundreds of DNS queries. In addition, as more internet-enabled ‘Things' get connected, people will rely on DNS to name and find their fridges, toasters and toilets. According to a recent IDG Research Services Survey this rate of traffic will only grow. What's driving t...
Nov. 25, 2014 07:00 PM EST Reads: 1,255
Enthusiasm for the Internet of Things has reached an all-time high. In 2013 alone, venture capitalists spent more than $1 billion dollars investing in the IoT space. With "smart" appliances and devices, IoT covers wearable smart devices, cloud services to hardware companies. Nest, a Google company, detects temperatures inside homes and automatically adjusts it by tracking its user's habit. These technologies are quickly developing and with it come challenges such as bridging infrastructure gaps, abiding by privacy concerns and making the concept a reality. These challenges can't be addressed w...
Nov. 25, 2014 04:30 PM EST Reads: 1,284
Explosive growth in connected devices. Enormous amounts of data for collection and analysis. Critical use of data for split-second decision making and actionable information. All three are factors in making the Internet of Things a reality. Yet, any one factor would have an IT organization pondering its infrastructure strategy. How should your organization enhance its IT framework to enable an Internet of Things implementation? In his session at Internet of @ThingsExpo, James Kirkland, Chief Architect for the Internet of Things and Intelligent Systems at Red Hat, described how to revolutioniz...
Nov. 24, 2014 07:00 PM EST Reads: 1,600
Bit6 today issued a challenge to the technology community implementing Web Real Time Communication (WebRTC). To leap beyond WebRTC’s significant limitations and fully leverage its underlying value to accelerate innovation, application developers need to consider the entire communications ecosystem.
Nov. 24, 2014 12:00 PM EST Reads: 1,486
The definition of IoT is not new, in fact it’s been around for over a decade. What has changed is the public's awareness that the technology we use on a daily basis has caught up on the vision of an always on, always connected world. If you look into the details of what comprises the IoT, you’ll see that it includes everything from cloud computing, Big Data analytics, “Things,” Web communication, applications, network, storage, etc. It is essentially including everything connected online from hardware to software, or as we like to say, it’s an Internet of many different things. The difference ...
Nov. 24, 2014 11:00 AM EST Reads: 1,621
Cloud Expo 2014 TV commercials will feature @ThingsExpo, which was launched in June, 2014 at New York City's Javits Center as the largest 'Internet of Things' event in the world.
Nov. 24, 2014 09:00 AM EST Reads: 1,635
SYS-CON Events announced today that Windstream, a leading provider of advanced network and cloud communications, has been named “Silver Sponsor” of SYS-CON's 16th International Cloud Expo®, which will take place on June 9–11, 2015, at the Javits Center in New York, NY. Windstream (Nasdaq: WIN), a FORTUNE 500 and S&P 500 company, is a leading provider of advanced network communications, including cloud computing and managed services, to businesses nationwide. The company also offers broadband, phone and digital TV services to consumers primarily in rural areas.
Nov. 23, 2014 07:30 PM EST Reads: 1,819
"There is a natural synchronization between the business models, the IoT is there to support ,” explained Brendan O'Brien, Co-founder and Chief Architect of Aria Systems, in this SYS-CON.tv interview at the 15th International Cloud Expo®, held Nov 4–6, 2014, at the Santa Clara Convention Center in Santa Clara, CA.
Nov. 23, 2014 12:00 PM EST Reads: 1,757
The major cloud platforms defy a simple, side-by-side analysis. Each of the major IaaS public-cloud platforms offers their own unique strengths and functionality. Options for on-site private cloud are diverse as well, and must be designed and deployed while taking existing legacy architecture and infrastructure into account. Then the reality is that most enterprises are embarking on a hybrid cloud strategy and programs. In this Power Panel at 15th Cloud Expo (http://www.CloudComputingExpo.com), moderated by Ashar Baig, Research Director, Cloud, at Gigaom Research, Nate Gordon, Director of T...
Nov. 23, 2014 07:45 AM EST Reads: 1,781
An entirely new security model is needed for the Internet of Things, or is it? Can we save some old and tested controls for this new and different environment? In his session at @ThingsExpo, New York's at the Javits Center, Davi Ottenheimer, EMC Senior Director of Trust, reviewed hands-on lessons with IoT devices and reveal a new risk balance you might not expect. Davi Ottenheimer, EMC Senior Director of Trust, has more than nineteen years' experience managing global security operations and assessments, including a decade of leading incident response and digital forensics. He is co-author of t...
Nov. 22, 2014 05:30 PM EST Reads: 1,530