A Phase I/II Study of Rituximab Plus Vincristine Sulfate Liposomes Injection in the Treatment of Relapsed or Refractory Aggressive Non Hodgkin's Lymphoma
- 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.
- 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
- 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