Rituximab and Combination Chemotherapy in Treating Older Patients With Diffuse Large B-Cell Lymphoma

OBJECTIVES:

Primary

• Determine the clinical response rate in older patients with previously untreated aggressive diffuse large B-cell stage II-IV lymphoma treated with rituximab, cyclophosphamide, pegylated doxorubicin hydrochloride liposome (HCl), vincristine, and prednisone.
• Determine the cardiotoxicity and myelosuppression of this regimen in these patients.

Secondary

• Determine disease-free survival and overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive rituximab intravenous (IV), cyclophosphamide IV over 1-1½ hours, pegylated doxorubicin HCl liposome IV over 1 hour, and vincristine IV on day 1, and oral prednisone on days 1-5. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 6 and continuing until blood counts recover OR pegfilgrastim SC once on day 6 (24 hours after the completion of chemotherapy). Treatment repeats every 21 days for up to 8 courses in the absence of unacceptable toxicity, disease progression, active hepatitis B virus infection, or hepatitis. Patients with no response OR who achieve less than a partial response after 4 courses are removed from the study.

Patients are followed at 1 month, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter.

PROJECTED ACCRUAL: A maximum of 80 patients will be accrued for this study within 27 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed diffuse large B-cell lymphoma

• Stage II, III, or IV disease
• Previously untreated disease
• Measurable or evaluable disease
• No primary central nervous system (CNS) lymphoma or follicular B-cell lymphoma

PATIENT CHARACTERISTICS:

Age

• 61 and over

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count > 1,000/mm^3*
• Platelet count > 100,000/mm^3* NOTE: * Unless due to lymphoma-related hypersplenism or bone marrow infiltration

Hepatic

• Bilirubin < 2 mg/dL
• Hepatitis B surface antigen negative
• Hepatitis B core antibody negative
• Hepatitis C Virus antibody negative

Renal

• Creatinine < 2 mg/dL

Cardiovascular

• left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram or ple gated acquisition (MUGA) scan
• No uncontrolled hypertension or cardiac symptoms
• Cardiologist consultation required for patients with stage A cardiac failure or any of the following known heart diseases:

• Diastolic dysfunction
• Prior coronary artery bypass graft
• Prior percutaneous transluminal coronary angioplasty
• Prior stent insertion
• Prior radiotherapy to the chest
• No myocardial infarction within the past 6 months
• No New York Heart Association class II-IV heart failure
• No uncontrolled angina
• No severe uncontrolled ventricular arrhythmias
• No clinically significant pericardial disease
• No acute ischemic or active conduction system abnormality by electrocardiogram (EKG)

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No psychiatric illness that would preclude study compliance or giving informed consent
• No other major life-threatening illness that would preclude study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• See Cardiovascular

Surgery

• See Cardiovascular