Rituximab and Combination Chemotherapy Combined With Yttrium Y 90 Ibritumomab Tiuxetan in Treating Older Patients With Previously Untreated B-Cell Lymphoma

OBJECTIVES:

• Determine the progression-free and overall survival of patients age 60 and over with previously untreated diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) combined with yttrium Y 90 ibritumomab tiuxetan.
• Determine the incidence of adverse experiences, hematologic toxicity (WBC, hemoglobin, and platelet nadirs; and transfusion requirements), cardiac toxicity (incidence of left ventricular dysfunction and cardiomyopathy by echocardiography), and the development of human antimouse antibody/human anti-chimeric antibody in patients treated with this regimen.
• Determine the predictive value of detecting minimal residual disease by molecular techniques for future relapse/recurrence in patients treated with this regimen.
• Determine the response rate of patients treated with this regimen.
• Determine the red blood cell transfusion requirements, change in hemoglobin from baseline, and incidence of anemia with prophylactic darbepoetin alfa support in patients treated with this regimen.
• Determine the conversion rate to complete remission in patients treated with ibritumomab tiuxetan who achieve a partial remission post-R-CHOP.
• Determine the effect of darbepoetin alfa on the quality of life of these patients.

OUTLINE: This is an open-label, nonrandomized study.

• Chemotherapy: Patients receive rituximab IV over 2-5 hours, cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1; oral prednisone on days 1-5 or 2-6; and filgrastim (G-CSF) subcutaneously (SC) on days 7-15. Patients also receive darbepoetin alfa SC on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
• Radioimmunotherapy: Patients receive rituximab IV over 3-5 hours and indium In 111 ibritumomab tiuxetan (IDEC-In2B8) IV over 10 minutes on day 0.

Patients undergo gamma camera imaging at 2-24 hours and 48-72 hours after the injection of IDEC-In2B8 to observe the flow of ibritumomab tiuxetan. If the flow is deemed safe, then patients receive yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 7.

Quality of life is assessed at baseline, before course 5 of chemotherapy, before radioimmunotherapy, and at 3 months.

Patients are followed every 3 months for 1 year and then every 6 months for 4 years.

PROJECTED ACCRUAL: A total of 65 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed diffuse large B-cell lymphoma, including any of the following subtypes:

• Centroblastic
• Immunoblastic
• T-cell/histiocyte-rich
• Lymphomatoid granulomatosis type
• Anaplastic large B-cell
• Plasmablastic
• Mediastinal
• Intravascular large B-cell lymphoma
• Previously untreated
• High-intermediate or high-risk disease, defined by an age-adjusted international prognostic index score of 2 or 3 (with 1 point each assigned for a ECOG greater than 1/Karnofsky less than 80%, lactate dehydrogenase greater than normal, and stage III or IV)
• Lymphomas with discordant histology and a diffuse large B-cell component are eligible
• Must have an initial diagnostic specimen that is CD20+
• At least Ann Arbor stage II disease

• No confinement of disease to an involved-field radiotherapy port (stage I or limited stage II disease)
• Bidimensionally measurable disease with at least 1 lymph node at least 2.0 cm by 2.0 cm by physical examination, CT scan, or positron-emission tomography
• Bone marrow cellularity greater than 15%
• No known brain or leptomeningeal metastases
• No primary effusion lymphomas

PATIENT CHARACTERISTICS:

Age

• 60 and over* NOTE: *Patients 60 to 65 years of age must be deemed ineligible for autologous stem cell transplantation

Performance status

• Karnofsky 50-100%

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin no greater than 2.0 mg/dL (except for Gilbert's disease)

Renal

• Creatinine no greater than 1.5 mg/dL* OR
• Creatinine clearance greater than 50 mL/min* NOTE: *Patients not meeting either criterion but who have renal insufficiency directly related to lymphomatous involvement of the kidneys or renal collecting system are allowed

Cardiovascular

• Cardiac ejection fraction at least 50% by echocardiogram
• No acute myocardial infarction within the past 3 months
• No uncontrolled hypertension
• No New York Heart Association class III or IV congestive heart failure
• No unstable angina pectoris

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• HIV negative
• B12 and folate greater than the lower limit of normal
• Transferrin saturation at least 15%
• Ferritin greater than 10 µg/L
• At least 6 weeks since prior RBC donation
• No active seizure disorder

• Prior seizure disorder allowed if free of antiseizure medication and evidence of seizure activity for the past 5 years
• No concurrent uncontrolled medical problems that would preclude administration of chemotherapy or radioimmunotherapy
• No other concurrent malignancy treated with chemotherapy or radiotherapy except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

• At least 4 weeks since prior RBC transfusion
• No prior biologic therapy
• No other concurrent biologic therapy

Chemotherapy

• No prior chemotherapy (one course of R-CHOP allowed)
• No other concurrent standard or investigational chemotherapy

Endocrine therapy

• No more than 7 consecutive days of prior steroids (premedication allowed for prior intravenous contrast allergy)
• No other concurrent corticosteroids

Radiotherapy

• No prior radiotherapy

Surgery

• Not specified