Premium
DEVEC: A PHASE II STUDY OF METRONOMIC CHEMOTHERAPY IN ELDERLY NON‐FIT PATIENTS WITH AGGRESSIVE B‐CELL LYMPHOMAS (PROMOTED BY FIL)
Author(s) -
Cox M.C.,
Musuraca G.,
Arcari A.,
Fabbri A.,
Gini G.,
Tani M.,
Tucci A.,
Marcheselli L.,
Storti S.,
Di Landro F.,
Battistini R.,
Anticoli Borza P.,
Casaroli I.,
Zoli V.,
Fabbri F.,
Aroldi A.,
Naso V.,
Bianchi M.,
Borgo E.,
Ferranti A.,
Dondi A.,
Levis A.,
Tafuri A.,
Merli F.
Publication year - 2017
Publication title -
hematological oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 44
eISSN - 1099-1069
pISSN - 0278-0232
DOI - 10.1002/hon.2440_8
Subject(s) - medicine , toxicity , chemotherapy , vinorelbine , rituximab , lymphoma , clinical trial , phases of clinical research , progression free survival , etoposide , cyclophosphamide , oncology , surgery , cisplatin
after high‐dose therapy or, in not transplant‐eligible patients (pts), after 1st‐line chemotherapy, represents an unmet clinical need. Therefore, we aimed at evaluating a salvage combination regimen (PREBEN/ PEBEN)) based on pixantrone, an aza‐anthracenadione recently approved in Europe for pts with multiply relapsed or refractory aNHL, etoposide, bendamustine and, in CD20+ tumors, rituximab. A preliminary pre‐trial experience on heavily pre‐treated pts with relapsed aNHL of B‐ or T‐cell phenotype showed good feasibility and efficacy and was previously reported. On this background, the Nordic Lymphoma Group launched an open label phase 1 (dose finding)/2 study (EudraCT no.2015‐000758‐39) testing the feasibility and efficacy of the PREBEN regimen in relapsed aNHL of B‐ or T‐cell phenotype. Here, we present the preliminary data of the first 12 enrolled pts. Methods: The trial design subdivides pts in ‘fit’ and ‘frail’ according to predefined criteria. ‘Fit’ patients enter phase 1 with a phase 2 expansion at maximum tolerated dose (MTD) level. ‘Frail’ patients enter directly phase 2 at baseline dose level. This consists of Pixantrone 50 mg/m i.v. day 1 + 8, Etoposide 100 mg i.v. day 1, Bendamustine 90 mg i.v. day 1 with or without the addition of Rituximab 375 mg/ m i.v. day 1. A maximum of 4–6 three‐weekly cycles is given. PET/ CT is performed after cycle 2 and at the end of therapy. Dose escalation is done according to a Bayesian design. Primary end‐points are MTD (phase 1) and overall response rate (ORR) (phase 2). Results: Of the 12 pts enrolled, 8 are males and 4 females. The age range is 39–80 yrs. The histological diagnosis at relapse was diffuse large B‐cell lymphoma (DLBCL) in 8 pts and peripheral T‐cell lymphoma in 4 pts. Two pts entered the phase 1 (‘fit’) trial at baseline level and 10 entered the phase 2 ‘frail’ part of the trial. All pts had IPI > 2 prior to salvage start. The mean N of previous regimens was 3 (range 1–5). Three pts had previously undergone autologous stem cell transplant. Ten pts have initiated/undergone therapy; two patients have not initiated their 1st cycle yet. Of the 10 treated pts, all had a partial (N = 6, 60%) or complete (N = 4, 40%) metabolic response (ORR 100%) after 2 cycles. One of the complete responses was seen in a previously transplanted pt with stage IV relapse including bone lesions. Response durations range between 4 and 7+ months. The treatment schedule was feasible and most patients received it on an outpatient basis. The most common grade 3–4 toxicity was of hematological type (mainly neutropenia and thrombocytopenia). At the now completed first dose level of phase 1, one MTD was recorded due to grade 4 neutropenia. Grade 3–4 infections were seen in 2 pts and were manageable. Conclusions: In this high‐risk population of relapsed aNHL, the PREBEN/PEBEN salvage schedule is feasible (outpatient regimen) and the preliminary efficacy data are promising.