Phase I Study of the Combination of Bendamustine, Rituximab, and Pixantrone in Patients With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

被引:4
作者
Heyman, Benjamin [1 ]
Rizzieri, David [1 ]
Adams, David J. [2 ]
De Castro, Carlos [1 ]
Diehl, Louis [1 ]
Li, Zhiguo [3 ]
Moore, Joseph [1 ]
Beaven, Anne [1 ]
机构
[1] Duke Univ, Sch Med, Dept Med, Div Hematol Malignancies & Cellular Therapy, Durham, NC 27706 USA
[2] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA
[3] Duke Univ, Sch Med, Dept Biostat & Bioinformat, Durham, NC USA
关键词
Anthracycline; Anthracenedoine; Heart failure; Left ventricular ejection fraction; Salvage; CYTOSINE-ARABINOSIDE; SALVAGE CHEMOTHERAPY; 3-DIMENSIONAL MODEL; PLUS RITUXIMAB; DES-LYMPHOMES; NCIC-CTG; GEMCITABINE; CISPLATIN; TRANSPLANTATION; DEXAMETHASONE;
D O I
10.1016/j.clml.2018.07.285
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
For patients with relapsed/refractory non-Hodgkin lymphoma, outcomes with standard chemotherapy are poor. New therapies with reduced toxicity are needed. We conducted a phase I clinical trial of the novel combination of BuRP (bendamustine, rituximab, and pixantrone) in patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Overall, the BuRP regimen was safe, with encouraging response rates warranting continued investigation at the highest dose level. Background: For patients with aggressive lymphomas who relapse after initial therapy, a durable response is rarely achieved with standard salvage therapies. Significant efforts have focused on the development of novel treatments with reduced toxicity. We conducted a phase I prospective single arm clinical trial of the novel combination of BuRP (bendamustine, rituximab, and pixantrone) in patients with relapsed/refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (NHL). Patients and Methods: Eligible patients included adults with biopsy-proven R/R B-cell NHL who met the criteria for treatment. Patients received bendamustine 120 mg/m(2), rituximab 375 mg/m(2), and pixantrone, per cohort dose, on day 1 for up to 6 cycles. Dose escalation used a 3 + 3 design, from a starting dose level of pixantrone 55 mg/m(2) to 115 mg/m at dose level 3. Results: Twenty-two patients were enrolled onto the study with a median follow-up of 7.9 months. The maximum tolerated dose was not reached, but the highest dose level of pixantrone of 115 mg/m(2) was well-tolerated. The most common grade 3/4 adverse events were neutropenia (27%) and thrombocytopenia (23%). The mean change in left ventricular ejection fraction was 2.5% (standard deviation, 5.51%; 95% confidence interval, 0.0%-4.9%). The overall response rate for the entire cohort was 37.5% (95% confidence interval, 15%-65%), but at the highest pixantrone dose, the overall response rate was 63%, with a complete response rate of 25%. Conclusion: The BuRP regimen was found to be safe in patients with R/R B-cell NHL. The favorable toxicity profile plus the encouraging response rates seen suggest that continued investigation of the highest dose level is warranted. (C) 2018 Elsevier Inc. All rights reserved.
引用
收藏
页码:679 / 686
页数:8
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