phase 1/2 study of vsli plus rituximab in patients with relapsed and/or refractory nhl

Conditions: Non-Hodgkin's Lymphoma; Diffuse Large B-cell Lymphoma; Mantle Cell Lymphoma

Summary: this was a phase 1/2 study performed at two clinical centers in the us and uk. it was a single arm, open label study evaluating vsli plus rituximab in adults with aggressive relapsed or refractory non-hodgkin's lymphoma.

the primary efficacy endpoint was objective response rate, defined as the proportion of patients with a response of cr + pr. duration of response, time to progression, and overall survival were analyzed. descriptive statistics were used for demographics, disease characteristics, treatment exposures, efficacy, and safety variables.

Eligibility criteria:
inclusion criteria: * histologically-confirmed diffuse large b-cell non-hodgkin's lymphoma (nhl), as defined by the revised european american lymphoma/who classification. this included: diffuse large b-cell, primary mediastinal large b-cell lymphoma with sclerosis,intravascular large b-cell lymphoma, immunoblastic b-cell lymphoma, t-cell rich b-cell lymphoma or anaplastic large b-cell lymphoma. in the us protocol only, patients who had transformation from an indolent lymphoma and those who had mantle cell lymphoma were eligible. * confirmation of cd20 expression on lymphoma cells. * eastern cooperative oncology group (ecog) ≤2. * one or more prior chemotherapy regimens. patients who had received prior rituximab therapy as part of an induction chemotherapy regimen or who had a previous response to rituximab as a single agent were eligible. * measurable disease in at least 1 site, which had not been previously irradiated. measurable disease was defined as at least 1 bidimensionally measurable lesion with clearly defined margins that were ≥1.5 cm in the largest dimension determined by physical examination or computed tomography (ct) scan. * total bilirubin and serum creatinine ≤2 times the uln. * absolute neutrophil count (anc) ≥0.5 × 109/l, and platelets ≥50 × 109/l. * 18 years of age or older. * women of childbearing potential who were willing to use an acceptable method of contraception throughout the course of the study. signed and dated informed consent form. exclusion criteria: * known transformation from an indolent lymphoma (uk protocol only). * eligible for conventional or high-dose chemotherapy with curative intent. * radiotherapy, chemotherapy, immunotherapy, or corticosteroids (\>10 mg/day of prednisone or equivalent) within the past 4 weeks. * any previous malignancies with less than a 5-year complete remission interval, except for curatively resected basal cell carcinoma or curatively resected in situ carcinoma of the uterine cervix. * history of or active cns-lymphoma, aids-related lymphoma, or any uncontrolled severe medical illness or infection. * history of neurologic disorders unrelated to chemotherapy (including familial neurologic diseases and acquired demyelinating disorders). * grade 3 or 4 sensory or motor neuropathy at screening related to prior chemotherapy. * major surgery (excluding that for diagnosis) within 4 weeks of enrollment. * pregnant or lactating women (women of childbearing potential underwent a pregnancy test). * allergy to vincristine, or other vinca alkaloids. * progressive disease while receiving or within 1 month of having received previous rituximab therapy (us protocol only). * hypersensitivity to any component of rituximab or to murine proteins (uk protocol only).

Keywords: nhl non-hodgkin's lymphoma diffuse large b-cell lymphoma mantle cell lymphoma