Randomised Comparisons, in Myeloma Patients of All Ages, of Thalidomide, Lenalidomide and Bortezomib Induction Combinations, and of Lenalidomide and Combination Lenalidomide Vorinostat as Maintenance
The last ten years has seen the introduction of a number of effective new anti-myeloma
agents into the clinical arena. These agents have been shown to be highly effective in the
relapse setting and now are being introduced as treatment earlier in the disease course.
This study aims to address in the randomised setting some of the key questions concerning
the use of thalidomide, bortezomib, lenalidomide and vorinostat in the initial treatment of
multiple myeloma patients.
Newly diagnosed patients of all ages with symptomatic myeloma requiring treatment are
For initial treatment, thalidomide in combination with cyclophosphamide and dexamethasone,
the UK gold standard, will be compared with the newer combination of lenalidomide,
cyclophosphamide and dexamethasone.
For patients with a sub-optimal response to initial therapy, the response to the proteasome
inhibitor bortezomib will be assessed, as previous studies have demonstrated that it is able
to induce responses and improve progression-free and overall survival in patients resistant
to standard chemotherapy. Patients young and fit enough to tolerate an autologous transplant
will then proceed to high dose melphalan with peripheral blood stem cell rescue and then on
to maintenance randomisation. Older or less fit patients will go directly to a maintenance
The value of lenalidomide and lenalidomide combined with vorinostat maintenance will then be
assessed by randomising eligible patients to receive either lenalidomide, lenalidomide
combined with vorinostat maintenance therapy, or close observation.
The primary end points of the study are overall and progression-free survival (OS and PFS).
Secondary end points include response and toxicity.
A number of laboratory based studies will also be performed in order to determine patient
specific factors predicting overall and progression-free survival and response to treatment.
Overall survial for induction chemotherapy comparisons is defined as the time from initial randomisation to the trial to death from any cause or last follow-up. Overall survival for maintenance therapy comparisons is defined from the time of maintenance randomisation.
United Kingdom: Medicines and Healthcare Products Regulatory Agency
EudraCT number: 2009-010956-93