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Results of a phase I-II study of fenretinide and rituximab for patients with indolent B-cell lymphoma and mantle cell lymphoma.

ABSTRACT: Fenretinide, a synthetic retinoid, induces apoptotic cell death in B-cell non-Hodgkin lymphoma (B-NHL) and acts synergistically with rituximab in preclinical models. We report results from a phase I-II study of fenretinide with rituximab for B-NHLs. Eligible diagnoses included indolent B-NHL or mantle cell lymphoma. The phase I design de-escalated from fenretinide at 900 mg/m2 PO BID for days 1-5 of a 7-day cycle. The phase II portion added 375 mg/m2 IV rituximab weekly on weeks 5-9 then every 3 months. Fenretinide was continued until progression or intolerance. Thirty-two patients were treated: 7 in phase I, and 25 in phase II of the trial. No dose-limiting toxicities were observed. The phase II component utilized fenretinide 900 mg/m2 twice daily with rituximab. The most common treatment-related adverse events of grade 3 or higher were rash (n = 3) and neutropenia (n = 3). Responses were seen in 6 (24%) patients on the phase II study, with a median duration of response of 47 months (95% confidence interval, 2-56). The combination of fenretinide and rituximab was well tolerated, yielded a modest overall response rate, but with prolonged remission durations. Further study should focus on identifying the responsive subset of B-NHL.

SUBMITTER: Cowan AJ

PROVIDER: S-EPMC5303179 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Results of a phase I-II study of fenretinide and rituximab for patients with indolent B-cell lymphoma and mantle cell lymphoma.

Cowan Andrew J AJ Stevenson Phillip A PA Gooley Ted A TA Frayo Shani L SL Oliveira George R GR Smith Stephen D SD Green Damian J DJ Roden Jennifer E JE Pagel John M JM Wood Brent L BL Press Oliver W OW Gopal Ajay K AK

British journal of haematology 20170105 4

Fenretinide, a synthetic retinoid, induces apoptotic cell death in B-cell non-Hodgkin lymphoma (B-NHL) and acts synergistically with rituximab in preclinical models. We report results from a phase I-II study of fenretinide with rituximab for B-NHLs. Eligible diagnoses included indolent B-NHL or mantle cell lymphoma. The phase I design de-escalated from fenretinide at 900 mg/m<sup>2</sup> PO BID for days 1-5 of a 7-day cycle. The phase II portion added 375 mg/m<sup>2</sup> IV rituximab weekly on ...[more]

PMID: 28055107

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Project description:BackgroundTemsirolimus is a mammalian target of rapamycin (mTOR) inhibitor with single-agent antitumour activity in patients with mantle cell lymphoma. We therefore tested its efficacy and toxicity in combination with rituximab (an antiCD20 antibody) in patients with relapsed or refractory mantle cell lymphoma.MethodsIn a phase 2 study, patients (aged ≥18 years) at 35 centres in the USA were given temsirolimus 25 mg/week, and rituximab 375 mg/m(2) per week for 4 weeks during the first cycle and thereafter a single dose of rituximab every other 28-day cycle. Both drugs were administered intravenously. Responding patients after six cycles could continue treatment for a total of 12 cycles, and were then observed without additional maintenance treatment. The primary endpoint was the proportion of patients with either rituximab-sensitive or rituximab-refractory disease who had at least a partial response. The analyses were done on all patients who were treated. The study was registered with ClinicalTrials.gov, number NCT00109967.Findings71 patients with mantle cell lymphoma were enrolled and 69 were assessable and were included in the final analysis. The overall response rate (ORR) was 59% (41 of 69 patients)-13 (19%) patients had complete responses and 28 (41%) had partial responses. The ORR was 63% (30 of 48; 95% CI 47-76) for rituximab-sensitive patients, and 52% (11 of 21; 30-74) for rituximab-refractory patients. The most common treatment-related grade 3 or 4 adverse events in rituximab-sensitive and rituximab-refractory patients were thrombocytopenia (eight [17%] and eight [38%], respectively), neutropenia (ten [21%] and five [24%], respectively), fatigue (eight [17%] and two [10%], respectively), leucopenia (six [13%] and three [14%], respectively), pneumonia (five [10%] and two [10%], respectively), lymphopenia (five [10%] and two [10%], respectively), pneumonitis (four [8%] and none, respectively), oedema (four [8%] and none, respectively), dyspnoea (three [6%] and two [10%], respectively), and hypertriglyceridaemia (three [6%] and two [10%], respectively).InterpretationmTOR inhibitors in combination with rituximab could have a role in the treatment of patients with relapsed and refractory mantle cell lymphoma.FundingNational Institutes of Health and the Predolin Foundation.

Dataset Information

Results of a phase I-II study of fenretinide and rituximab for patients with indolent B-cell lymphoma and mantle cell lymphoma.

Publications

Results of a phase I-II study of fenretinide and rituximab for patients with indolent B-cell lymphoma and mantle cell lymphoma.

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