January 26, 2010
Perspectives on Recent Clinical Trials Development, Susan Kelley, MD
Recently, two new drugs have entered into phase III clinical trials, representing the final stages of clinical development intended to create a data dossier for submission to health regulators, such as the US FDA as part of the approval process for new drugs. These new trials will include patients with relapsed (recurrent) MM from the US and around the world. One trial, sponsored by Keryx and AEterna Zentaris, evaluates the combination of Velcade (bortezomib) and KRX-0401 (perifosine), a novel inhibitor of key signaling pathways involved in tumor cell growth. The second new phase III trial evaluates the combination of Velcade with panobinostat, an inhibitor of histone deacetylase, which is thought to influence gene messaging in tumor growth processes (Novartis). Myeloma patients should be encouraged by the increasing numbers of myeloma clinical studies and the transition of new agents into late stage drug trials. The challenge now is to ensure that the clinical trials that are being conducted can be enrolled rapidly. MMRF and MMRC will continue to work closely with the sponsors and clinical investigators on these trials to improve patient enrollment to these and other ongoing trials.
There have also been several announcements of new study results confirming the importance of “maintenance” therapy administered after initial chemotherapy and stem cell transplant. This maintenance therapy frequently consists of 1-2 drugs, including an IMID, such as Revlimid (lenalidomide), administered for up to 2-3 years after initial response is documented. Preliminary data were presented by Professor Palumbo from the Celgene MM 015 trial at ASH. Then, during later December and early January, press releases were issued by Celgene with the IFM (France) and by the US NCI (cooperative group CALGB) about two additional studies (one in Europe and one in US), where patients receiving maintenance with Revlimid had a longer time until myeloma recurrence than patients who were not receiving long-term maintenance treatment.
Furthermore, several new clinical trials are evaluating the possible role of treatment with new or existing drugs for patients with Smoldering (Stage I) MM, and preliminary positive data were presented at ASH in December, from a trial evaluating Revlimid and dexamethasone, with very positive outcome, but it was an analysis on only 40 patients so it is premature to conclude that smoldering patients should receive treatment.
Finally, data from phase I-II (early clinical development) trials facilitated by the MMRC were also presented at ASH. The new drugs/studies presented included updates on the ongoing trials with carfilzomib, elotuzumab, Torisel, NPI-0052, pomalidomide and combined treatment using Revlimid, Velcade, Doxil and dexamethasone. There was an important session on advances in genomics studies and preliminary findings from the ongoing MMRF Genomics Initiative were presented.
So, what should patients take away from these recent data? The data from several of these important “maintenance” protocols will be released for greater scrutiny by the medical community during 2010. It is important that all patients currently receiving treatment for newly diagnosed MM speak with their hematologists/oncologists about the role of maintenance therapy and whether they should be considered for maintenance treatment starting some time after completion of stem cell transplant (if transplanted) or after attaining the maximal benefit from induction chemotherapy. As always, please ask your physicians about clinical trials which might suit your stage of disease, whether you are a newly diagnosed patient or a patient whose MM has recurred after initial therapy. There are important new drugs emerging and increased trial participation rates will mean that the important results from these trials can become available sooner.