In:
British Journal of Haematology, Wiley, Vol. 175, No. 1 ( 2016-10), p. 55-65
Kurzfassung:
This phase Ib, dose‐escalation study investigated the maximum tolerated dose ( MTD ), recommended phase II dose ( RP 2D), safety, pharmacokinetics ( PK ) and preliminary efficacy of the pan‐class I phosphoinositide 3‐kinase ( PI 3K) and mechanistic target of rapamycin ( mTOR ) inhibitor voxtalisib [30 or 50 mg twice daily ( BID )], in combination with rituximab (voxtalisib+rituximab) or rituximab plus bendamustine (voxtalisib+rituximab+bendamustine), in relapsed or refractory indolent B‐cell non‐Hodgkin lymphoma ( NHL ), mantle cell lymphoma and chronic lymphocytic leukaemia ( CLL ). MTD and RP 2D of voxtalisib were determined using a 3 + 3 dose‐escalation design. Adverse events ( AE s), plasma PK and disease response were recorded. Thirty‐seven patients were enrolled. The RP 2D of voxtalisib in combination with rituximab or rituximab+bendamustine was 50 mg BID . Four patients experienced a total of five dose‐limiting toxicities. The most frequent AE s were nausea (45·9%), fatigue (37·8%) headache (32·4%) and pyrexia (32·4%). The most frequent grade ≥3 AE s were neutropenia (27·0%), thrombocytopenia (24·3%), anaemia (16·2%) and febrile neutropenia (10·8%). Voxtalisib PK parameters were not affected by co‐administration with rituximab or rituximab+bendamustine. Of 35 efficacy‐evaluable patients, four (11·4%) achieved complete response and 13 (37·1%) achieved partial response. Voxtalisib, in combination with rituximab or rituximab+bendamustine, demonstrated an acceptable safety profile and encouraging anti‐tumour activity in relapsed or refractory B‐cell malignancies.
Materialart:
Online-Ressource
ISSN:
0007-1048
,
1365-2141
DOI:
10.1111/bjh.2016.175.issue-1
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2016
ZDB Id:
1475751-5
