"At a pre-planned interim analysis, an independent data monitoring committee determined that the study met its primary endpoint showing that GA101 plus chlorambucil helped people live significantly longer without their disease worsening (progression-free survival; PFS) compared to MabThera/Rituxan plus chlorambucil. The CLL11 study is being conducted in cooperation with the German CLL Study Group (GCLLSG). These final data were reached well ahead of the target completion date in 2014 as a result of the magnitude of difference seen between the two study arms. No new safety signals for GA101 or MabThera/Rituxan were identified in this analysis, and adverse events were similar to those observed in the first stage of the study which was previously reported earlier this year."
The FDA has granted Obinutuzumab GA101 in CLL both Breakthrough Therapy Designation and Priority Review.
Marketing applications have also been submitted to other regulatory authorities, including the European Medicines Association (EMA), in April 2013. In the United States, Genentech has opened an Expanded Access Program (EAP) to provide GA101 to people with CLL under certain circumstances while the company seeks regulatory approval.
' Adding the investigational monoclonal antibody obinutuzumab (GA101, Genentech) to chlorambucil in elderly patients with chronic lymphocytic leukemia (CLL) more than doubled time to disease progression in a phase 3 trial.
"Effectively, this ends the era of chlorambucil monotherapy," study author Valentin Goede, MD, clinical scientist in the Department of Hematology at the University of Cologne, Germany, told Medscape Medical News.
Dr. Goede presented the first set of results from the CLL11 trial during the Presidential Symposium here at the 18th Congress of the European Hematology Association.'
"This finding suggests an 86% reduction in the risk for a progression, relapse, or death in the obinutuzumab arm," Dr. Goede pointed out.
He noted that these data, particularly the progression-free survival for the obinutuzumab group, might improve with time because the data are still immature.'
Marketing applications have been submitted on the basis of the CLL11 data to regulatory authorities, including the European Medicines Association and the US Food and Drug Administration (FDA). A launch in the United States is expected by the end of this year.
Thanks for this appreciate the updates, especially being in the older age group. However, did I read the article correctly that the new drug if passed will not be available untl Dec 20 ?. Still getting to grips with all the information, treatments etc.
Best to talk to your Cardiff consultant. Prof Fegan was is involved with the CLL11 and will be able to give you a clear picture of the Welsh picture. There will be further hurdles to overcome following licensing the treatment has to go through appraisal and approval by NICE. I believe it will take longer for us?
In the meantime RIALTO I believe is running in the UK, allowing access to a similar combination .
A Phase III randomised trial to compare Ofatumumab plus Chlorambucil (O-Ch) and Ofatumumab and Benamustine (O-B) for patients not considered fit for FCR.
From the earlier thread:
Professor Chris Fegan and patient discuss the promising results of the clinical trial of obinutuzumab (GA101) in combination with Chlorambucil cardiffandvaleuhb.wales.nhs... Cardiff CLL Research Group cardiffcll.wordpress.com
The paper will be presented at ASH conference in December. FDA approval will follow, perhaps early 2014. Then approvals in the EU and other countries will follow...
There is no set timeline to market, unfortunately.
Yes buses often arrive together. Good to see competition for the Rituximab replacement (lets not also forget generic versions of Rituximab will also join the mix too and add to available options). Good to have two humanised MAB’s that are more effective at targeting CD20 than Rituximab that also use a different part of the molecule., adding to treatment options.
Here is some information about progress with the GSK equivalent: Ofatumumab
Ofatumumab is also gaining ground and has met its final endpoint in trials with chlorambucil. final results of its phase 3 study in combination with chlorambucil will be released later this year. Both are now lining up for approval in combination with chlorambucil as first line treatments for those unsuitable for FCR.
“The company said a total of 447 patients were enrolled in the study. A 9.3 month improvement in the time a patient lived without worsening of their disease was seen in patients randomized to ofatumumab and chlorambucil compared to patients randomized to chlorambucil alone.”
Genmab news
GSK and Genmab Announce Positive Top-line Results from Pivotal Study of ARZERRA® (ofatumumab) Combined with Chlorambucil in Previously Untreated Chronic Lymphocytic Leukemia
• Median 22.4 month progression free survival in patients treated with ofatumumab plus chlorambucil, an improvement of 9.3 months compared to chlorambucil alone
• No unexpected safety findings
Copenhagen, Denmark and London UK; May 29, 2013 — Genmab A/S (OMX: GEN) and GlaxoSmithKline plc (GSK) announced today that their Phase III study of ARZERRA® (ofatumumab) in combination with chlorambucil versus chlorambucil alone in patients with previously untreated chronic lymphocytic leukemia (CLL) met its primary endpoint of progression free survival (PFS) as assessed by an Independent Review Committee (IRC).
A total of 447 patients were enrolled in the study. A 9.3 month improvement in the time a patient lived without worsening of their disease (median PFS) was seen in patients randomized to ofatumumab and chlorambucil compared to patients randomized to chlorambucil alone (22.4 months vs. 13.1 months; Hazard Ratio 0.57; p<0.001).
There were no unexpected safety findings. The most common (=1%) serious adverse events as reported by the investigator within 60 days of last treatment were neutropenia [including febrile neutropenia] (5%), anaemia (4%), pneumonia (4%), and pyrexia (2%). Infusion reactions were mild to moderate in severity with 3% of infusion reactions reported as serious.
"We are delighted with the positive results from this trial which we believe may lead to ofatumumab plus chlorambucil as an additional treatment option for the care of patients with CLL," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "We look forward to submitting the study results, including secondary endpoints, to the International Workshop on CLL (iwCLL) in Cologne, Germany this September."
"As the aim of treating CLL, particularly in the frontline setting, is to maximize progression free survival while minimizing side effects, we are therefore encouraged by these promising results," said Dr. Kathy Rouan, Vice President BioPharmaceutical Development, GlaxoSmithKline. "We are planning regulatory submissions in the EU, US, and other regions in the coming months."
About the study
This Phase III study (NCT00748189) included patients with previously untreated CLL considered inappropriate for fludarabine-based therapy. Patients in the study were randomized 1:1 to treatment with up to twelve cycles of ofatumumab in combination with chlorambucil or up to twelve cycles of chlorambucil alone. The primary endpoint of the study was PFS according to the International Workshop for Chronic Lymphocytic Leukaemia (IWCLL) updated 2008 National Cancer Institute-sponsored Working Group (NCIWG) guidelines, using an independent endpoints review committee.
This article includes the following comments by Dr Kanti Rai (of Rai CLL staging fame)
"Time to rethink chlorambucil?
This trial was an extremely interesting, large sample size, multinational planned and executed trial.
Patients with comorbidities, the population selected for this study, are the people with chronic lymphocytic leukemia who need to be addressed. They form the largest majority of the CLL population. This study confirms that chlorambucil, which we in the United States have virtually thrown out of the window as totally ineffective, may not be so if you use it in combination with an anti-CD20 monoclonal antibody. These are excellent results that we have to keep in mind."
Dr. Kanti Rai is chief of hematology-oncology at Long Island Jewish Medical Center in New Hyde Park, N.Y. He was the invited discussant of the study and disclosed serving as a consultant or advisor to Celgene, Genentech, and Teva and receiving honoraria from Celgene, Cephalon, and Genentech.
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