Rituximab and Denileukin Diftitox in Treating Patients With Previously Untreated Stage III or Stage IV Follicular B-Cell Non-Hodgkin's Lymphoma

OBJECTIVES:

Primary

• Determine the response rate (complete response [CR], unconfirmed CR, and partial response) in patients with previously untreated stage III or IV follicular B-cell non-Hodgkin's lymphoma treated with rituximab and denileukin diftitox.
• Assess the overall survival, time-to-progression, duration of response, and time-to-new therapy in patients treated with this regimen.

Secondary

• Determine whether this regimen depletes or inhibits the function of regulatory T cells in these patients.

OUTLINE: This is a multicenter study.

Patients receive rituximab IV on days 1, 8, 15, and 22. Patients also receive denileukin diftitox IV over 15-60 minutes on days 1-5. Treatment with denileukin diftitox repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Blood is collected at baseline; on day 1 of courses 2-4; and 1 and 4 months after completion of study treatment for research studies. Research studies include analysis of peripheral blood lymphocyte subsets expressing CD3, CD4, CD8, CD19, CD25, and CD26 by flow cytometry; quantitation of CD4+, CD25+ regulatory T cells by flow cytometry; tumor-specific γ-interferon-secreting T cells by enzyme-linked immunospot assay; tumor-specific cytotoxic T-lymphocyte activity; and immune activation by enzyme-linked immunosorbent assay.

After completion of study treatment, patients are followed periodically for up to 5 years after registration.

PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Pathologically confirmed follicular B-cell non-Hodgkin's lymphoma (NHL)

• Stage III or IV disease
• Grade 1 or 2 disease
• Previously untreated disease
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques

• Clearly defined bidimensional diameter ≥ 2 x 2 cm on physical examination OR > 2.0 cm in 1 of the dimensions by CT scan, MRI, or plain radiograph imaging
• Splenic enlargement may be used as a measurable parameter if the spleen is palpable ≥ 3 cm below the left costal margin
• Circulating tumor cells < 5,000/mm³
• Must have paraffin-embedded tissue blocks/slides available
• No CNS lymphoma

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 1 year
• WBC ≥ 3,400/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 10.0 g/dL
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 3 times ULN
• AST ≤ 3 times ULN
• Creatinine ≤ 1.5 times ULN
• Albumin ≥ 3 g/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 1 year after completion of study therapy
• No HIV infection
• No other active malignancies
• No active uncontrolled infection
• No known hypersensitivity to denileukin diftitox or any of its components, including diphtheria toxin, aldesleukin, or excipients

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy, immunotherapy, vaccines, or radiotherapy for NHL