Gemcitabine Hydrochloride, Cyclophosphamide, Vincristine Sulfate, Prednisolone, and Rituximab in Treating Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma
Gemcitabine Hydrochloride, Cyclophosphamide, Vincristine Sulfate, Prednisolone, and Rituximab in Treating Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma
RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride, cyclophosphamide,
 vincristine sulfate, and prednisolone, work in different ways to stop the growth of cancer
 cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies,
 such as rituximab, can block cancer growth in different ways. Some block the ability of
 cancer cells to grow and spread. Others find cancer cells and help kill them or carry
 cancer-killing substances to them. Giving more than one drug (combination chemotherapy)
 together with rituximab may kill more cancer cells.

 PURPOSE: This phase II trial is studying giving gemcitabine hydrochloride, cyclophosphamide,
 vincristine sulfate, and prednisolone together with rituximab to see how well it works 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