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

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).