The EORTC Cutaneous T-Cell Lymphoma (CTCL) Platform

Primary Cutaneous T-cell Lymphomas (CTCLs) are a heterogenous group of lymphomas, as outlined in the WHO classification. Due to the rarity of CTCL, very few prospective randomized trials have been performed for this disease. EORTC consensus recommendations for the treatment of early CTCL have been published, but treatment of advanced stage disease remains largely empirical, based on small non-randomized, uncontrolled studies with uncertain response data and limited chances to affect clinical practice.

The CTCL platform has been designed by the EORTC Cutaneous Lymphoma Task Force to address critical unadressed questions to move forward the standards of care of CTCL in advanced stage disease. It was built following a sequential approach. Following a European consensus defining the key clincial questions to improve disease control in CTCL, ideas regarding the biology of the disease and all possible emerging targets which may lead to a better understanding of the disease were explored. The candidate targets were selected and prioritized by their scientific and clinical relevance. The maturity and relevance of agents in development to tackle these pathways and targets were analyzed. Methodologically and statistically robust clinical trials were designed to allow the enrollment of patients through the evolution of their disease. Endpoints and translational research programs that could address and help identify mechanisms of action and clinical efficacy were also evaluated as to feasibility and scientific relevance. This comprehensive process lead to the design of early phase randomized trials on solid scientific grounds with the use of innovative drugs. Study protocol 21081 is a multicenter, randomized, open-label, phase III study and is suitable for patients who have not previously had other intravenous chemotherapy, and are therefore relatively treatment-naïve. The accrual goal is 105 patients. The objective of this trial is to test the hypothesis that lenalidomide is able to increase progression free survival in patients achieving a complete (CR) or partial (PR) response after standardized debulking treatment. A sister protocol, 21082, is addressed to patients who have had previous chemotherapy. Patients in that study will be treated with the histone deacetylase inhibitor vorinostat, with or without the addition of the proteosome inhibitor bortezomib. The primary objective of this trial will be to determine if the combination of bortezomib plus vorinostat is more effective than a histone deacetylase inhibitor alone in terms of prolonging progression free survival.

The presentation will address details of the disease biology which gave rise to these trials and the selection of innovative agents, the procedures of the strategy adopted and the challenges of designing methodologically valid trials addressing this rare disease.

Ortiz-Romero: MSD: Consultancy; Ferrer: Honoraria.