Phase 1/2 Study of VSLI Plus Rituximab in Patients With Relapsed and/or Refractory NHL

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).