vincristine sulfate liposome injection (marqibo®), bendamustine and rituximab-phase i trial in indolent b-cell lymphoma

Conditions: Lymphoma, Non-Hodgkin; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, Small-Cell; Waldenstrom Macroglobulinemia; Lymphoma, B-Cell, Marginal Zone

Summary: this study evaluates addition of vincristine sulfate liposome injection (marqibo®) to the standard regimen of bendamustine and rituximab in adult patients with indolent b-cell lymphoma. this is a dose-escalation study.

bendamustine-rituximab is a standard chemotherapy regimen for treatment of many indolent b-cell lymphomas, but most patients experience a recurrence of the lymphoma. vincristine sulfate has been a traditional component of chemotherapy regimens in non-hodgkin lymphoma and it is possible that adding it to the bendamustine-rituximab regimen might provide a better quality of remissions or longer duration of remissions with acceptable toxicity. this is a phase 1, single-center, open-label, single-arm trial in patients with indolent b-cell non-hodgkin lymphoma otherwise appropriate for bendamustine-rituximab as initial or subsequent line of therapy. patients will receive the of rituximab and bendamustine in combination with escalating doses of vincristine sulfate liposome injection (marqibo®). the objective of this study is to assess safety of this combination by establishing the maximum tolerated dose of vincristine sulfate liposome injection (marqibo®) in the combination.

Eligibility criteria:
inclusion criteria: * histologically confirmed indolent b-cell non-hodgkin lymphoma. * radiological measurable disease. * previous treatment for lymphoma is allowed, with the exception of use of bendamustine within 6 months or any prior use of vincristine sulfate liposome injection * eastern cooperative oncology group performance status 0 or 1; * life expectancy of at least 6 months; * adequate organ and marrow function; * women of child-bearing potential and men must agree to use adequate contraception. * ability to understand and the willingness to sign a written informed consent document. exclusion criteria: * history of allergic reactions attributed to any drug used in the study. * any lymphoma-directed therapy within 4 weeks. * any prior treatment with vincristine sulfate liposome injection. * prior treatment with bendamustine or vincristine sulfate within 180 days of enrollment. * patients who are receiving any other investigational agents with the exception of endocrine therapy for breast or prostate cancer. * central nervous system involvement. * peripheral sensory or motor neuropathy. * history of a demyelinating condition. * positive test for the human anti-chimeric antibody (haca). * patients receiving any medications or substances that are strong inhibitors or inducers of cytochrome p450, family 3, subfamily a (cyp3a) enzyme are ineligible. * uncontrolled intercurrent illness. * prisoners. * pregnant or breast-feeding women. * known human immunodeficiency virus (hiv) or active hepatitis b infection * any prior or active cancer, which in the opinion of the investigator would preclude safe participation in this study.

Keywords: bendamustine rituximab vincristine sulfate vincristine sulfate liposome injection phase i escalation with overdose control