Study terminated due to lack of response at the first efficacy analysis

Rituximab has been demonstrated to sensitize drug-resistant NHL cells to the cytotoxic actions of several chemotherapy agents by enhancing sensitivity of tumor cells to chemotherapy-induced apoptosis. Gemcitabine, a nucleoside analog that is used in several other malignancies, has shown very promising activity in patients with refractory Hodgkin's disease and low-grade NHL. The combination of rituximab and gemcitabine may have synergistic cytotoxic action in patients with relapsed or refractory DLBCL and possibly lead to improved response rates and demonstrable clinical benefit.

This trial will investigate the efficacy the combination of rituximab and gemcitabine in treating patients with relapsed or refractory DLBCL.

OUTLINE: This is a multi-center study.

• Rituximab 375 mg/m2 day 1 of 21 day cycle
• Gemcitabine 1000 mg/m2 days 1 and 8 of 21 day cycle

Subgroup 1. Relapsed after responding to first line chemotherapy, who are not candidates for salvage high-dose chemotherapy.

Subgroup 2. Failure to achieve a complete response or relapsed after responding to salvage chemotherapy (any number of salvage regimens allowed), who are not candidates for high-dose chemotherapy.

Subgroup 3. Refractory to first line chemotherapy and/or 1 (one) salvage chemotherapy regimen.

Subgroup 4. Progression after high-dose chemotherapy. Patients with progressive disease within 3 months of high-dose chemotherapy are not allowed.

Performance Status: ECOG performance status 0, 1, 2

Life expectancy: Not specified

Hematopoietic:·

• ANC ≥ 1,000/mm3·
• Platelets ≥ 100,000/mm3

Hepatic:·

• Total bilirubin ≤ 2.0 x ULN·
• ALT and AST ≤ 3 x ULN unless lymphoma involves the liver on CT scan then AST and ALT can be < 5 x ULN

Renal:·

• Serum creatinine ≤ 2.0 mg/dl (except for patients on dialysis)

Cardiovascular:·

• Not specified

Pulmonary:·

• Not specified

Inclusion Criteria:

• Biopsy-proven DLBCL which meet the criteria of any of the 4 subgroups
• Transformed DLBCL from a previous indolent NHL which meet the criteria of any of the 4 subgroups and have received at least one standard chemotherapy regimen for aggressive NHL or a biopsy upon progression of disease has been obtained to confirm the presence of DLBCL. The concomitant presence of a component of low grade lymphoma will NOT exclude participation
• Measurable disease per Standardized Response Criteria for Non-Hodgkin's Lymphoma
• Prior gemcitabine therapy is allowed.
• Negative pregnancy test

Exclusion Criteria:

• No history of life-threatening reactions to rituximab.
• No history of gemcitabine intolerance; prior gemcitabine therapy is allowed.
• No history of malignancy in the last 5 years (basal cell carcinoma of the skin excluded).
• No central nervous system or cerebrospinal fluid involvement
• No other investigational drugs received within 30 days prior to being registered for protocol therapy.
• No active infections.
• No current breastfeeding