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DEVEC: A PHASE II STUDY OF METRONOMIC CHEMOTHERAPY IN ELDERLY NON‐FIT PATIENTS WITH AGGRESSIVE B‐CELL LYMPHOMAS (PROMOTED BY FIL)

2017; Wiley; Volume: 35; Issue: S2 Linguagem: Inglês

10.1002/hon.2440_8

1099-1069

Maria Christina Cox, Gerardo Musuraca, Annalisa Arcari, Alberto Fabbri, Guido Gini, Monica Tani, Alessandra Tucci, Luigi Marcheselli, Sergio Storti, Francesca Di Landro, R. Battistini, Paola Anticoli Borza, Ivana Casaroli, Valerio Zoli, Francesca Fabbri, Andrea Aroldi, Virginia Naso, Maria Paola Bianchi, E Borgo, Antonella Ferranti, Alessandra Dondi, Alessandro Levis, Agostino Tafuri, Francesco Merli,

CAR-T cell therapy research

Background: There is an unmet need for active treatments in elderly, non-FIT patients, with aggressive lymphomas, allowing to preserve patient's Quality of life (QoL). Moving forward to setting up a suitable schedule, we devised a metronomic chemotherapy (MTN-CHT) protocol, termed DEVEC, consisting of prednisolone (PDN), cyclophosphamide (CTX), etoposide (ETO), oral vinorelbine (VRN) ± rituximab(RTX). Since February 2011, this MTN-CHT schedule, was adopted in six clinical centres affiliated with the FIL. Candidate for this palliative schedule were aggressive B and T cell lymphoma patients, considered unfit for standard chemotherapies. Forty-two patients (31 DLBCL and 11 PTCL), with a median age of 79 years, were evaluated for outcome analysis. The schedule was well tolerated even in frail pts; hematologic toxicity was moderate and manageable with GF. The rate of extra-hematologic toxicity of grade ≥ 3 was 19%, mostly due to infections. Only 3/42 (7%) pts discontinued treatment because of toxicity or death. The overall response rate (ORR) was 64.3% including 23.8% CR, 4.7% unconfirmed CR (uCR) and 38% PR. The median overall survival (OS) and progression free survival (PFS) were 15 (95% CI = 8.645–21.355) and 10 (CI 95% = 5.520–14.480) months, respectively. On the basis of these results and giving the lack of MTN-CHT trials in lymphoma patients, the elderly commission of the FIL released in November 2016 the DEVEC trial (EUDRACT 2016-003703-62). Methods/Design: This is an open label, non-randomized, multicentre, phase II study, to evaluate the efficacy and safety of DEVEC oral schedule (fig1) in large B-cell (LBCL) and Burkitt lymphoma (BL) diagnosed in elderly unfit and frail patients who are R/R after previous treatment, and in super-frail patients at disease onset. Patients will be enrolled according to Bryant & Day two-stage optimal design.Co-Primary Objectives: 1) To explore the activity of the DEVEC induction + maintenance schedule; 2) To explore the safety of the DEVEC induction + maintenance schedule.Secondary Objectives: To evaluate the ORR (CR, Cru, PR) and the Clinical Benefit evaluated at the end of induction (EOI) cycles. OS, PFS, EFS, DFS, to assess QoL. Treatment Schedule: A) Induction phase: six courses (q 28 days) of PDN + ETO + VRN + CTX, ±RTX. Patients in PR and SD after 2 cycles will continue with additional 4 courses. At the end of the induction phase patients in ≥PR will continue treatment with B) Maintenance phase: six courses of PDN + VRN + CTX. (q28 days). Primary Endpoints: The primary efficacy endpoint is defined in terms of CRR (CR + Cru rate). The primary safety endpoint is defined as incidence, nature, and severity of adverse events. Keywords: Chemotherapy; diffuse large B-cell lymphoma (DLBCL); elderly.