Gemcitabine Hydrochloride, Cyclophosphamide, Vincristine Sulfate, Prednisolone, and Rituximab in Treating Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma

OBJECTIVES:

• To determine whether rituximab, in combination with non-cardiotoxic chemotherapy comprising gemcitabine hydrochloride, cyclophosphamide, vincristine sulfate, and prednisolone, is efficacious in a group of patients who are unfit for CHOP chemotherapy.

OUTLINE: This is a multicenter study.

Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8; cyclophosphamide IV, vincristine sulfate IV, and rituximab IV on day 1; and oral prednisolone once daily on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 1 year.

DISEASE CHARACTERISTICS:

• Histologically confirmed CD20-positive diffuse large B-cell non-Hodgkin lymphoma (DLBCL) according to the current WHO classification, including all morphological variants

• Newly diagnosed disease
• Bulky stage IA-IV disease

• No non-bulky stage IA disease
• Measurable disease
• Not eligible for CHOP chemotherapy due to impaired cardiac function

• Cardiac status that does not allow the administration of 8 courses of R-CHOP chemotherapy, as defined by 1 of the following criteria:

• Ejection fraction less than 50% as assessed by either ECHO or MUGA scan
• NYHA class III-IV
• No high-grade transformation of low-grade lymphoma
• No symptomatic central nervous system or meningeal involvement by the lymphoma
• No AIDS-related lymphoma

PATIENT CHARACTERISTICS:

• ECOG performance status 0-3
• Life expectancy > 3 months
• Platelet count > 100 x 10^9/L
• WBC > 3 x 10^9/L
• Neutrophils > 1.5 x 10^9/L (unless elevated level attributed to bone marrow infiltration by lymphoma)
• Serum bilirubin < 50 μmol/L
• Transaminases < 2.5 times upper limit of normal (unless elevated level attributed to lymphoma)
• Glomerular filtration rate > 30 mL/min
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other concurrent uncontrolled medical condition
• No active malignant disease, other than non-melanotic skin cancer or carcinoma in situ of the uterine cervix, within the past 10 years
• No positive serology for HIV
• No medical or psychiatric conditions that compromise the patient's ability to give informed consent

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy, radiotherapy, or other investigational drug for this indication