RATIONALE: Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining more than one monoclonal antibody may kill more cancer cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining two different monoclonal antibodies in treating patients who have relapsed or refractory follicular non-Hodgkin's lymphoma.

OBJECTIVES:

• Determine the safety profile and recommended phase II dose of IDEC-114 monoclonal antibody and rituximab in patients with relapsed or refractory follicular non-Hodgkin's lymphoma.
• Determine the pharmacokinetics of this regimen in these patients.
• Determine the efficacy of this regimen in these patients.
• Determine the immunogenicity of this regimen in these patients.

OUTLINE: This is an open-label, multicenter, dose-escalation study of IDEC-114 monoclonal antibody (IDEC-114).

• Phase I: Patients receive IDEC-114 IV over 1 hour on days 3, 8, 15, and 22 and rituximab IV on days 1, 8, 15, and 22.

Cohorts of 3-6 patients receive escalating doses of IDEC-114 until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

• Phase II: Patients receive IDEC-114 at the MTD and rituximab as in phase I. Patients are followed at days 29, 36, 43, and 50; months 3 and 6; every 3 months for 1.5 years; and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 39-48 patients (9-18 patients for phase I and 30 patients for phase II) will be accrued for this study.

• Biological: galiximab
• Biological: rituximab

DISEASE CHARACTERISTICS:

• Histologically confirmed follicular non-Hodgkin's lymphoma (NHL)

  • Relapsed after or refractory to primary therapy
• Progressive disease after at least 1 prior standard therapy, including chemotherapy, radiotherapy, biologic therapy, or bone marrow or stem cell transplantation

• Bidimensionally measurable disease

  • At least one lesion at least 2.0 cm
• No disease refractory to prior rituximab
• No pleural or peritoneal effusion with positive cytology for lymphoma
• No prior aggressive NHL or mantle cell lymphoma
• No chronic lymphocytic leukemia
• No CNS lymphoma

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• WHO 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Hemoglobin at least 8.0 g/dL
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 75,000/mm^3

Hepatic

• Bilirubin no greater than 2.0 mg/dL
• AST and/or ALT no greater than 2 times upper limit of normal

Renal

• Creatinine no greater than 2.0 mg/dL
• No hydronephrosis

Cardiovascular

• No congestive heart failure
• No New York Heart Association class III or IV heart disease
• No myocardial infarction within the past 6 months

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 12 months after study participation
• HIV negative
• No other primary malignancy requiring active treatment (except hormonal therapy)
• No active uncontrolled bacterial, viral, or fungal infection
• No other medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• More than 3 weeks since prior biologic therapy for cancer
• More than 6 months since prior antibody therapy for lymphoma
• More than 6 months since prior bone marrow or stem cell transplantation
• No prior IDEC-114 or other anti-CD80 antibody

Chemotherapy

• See Disease Characteristics
• More than 3 weeks since prior chemotherapy for cancer (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

• More than 3 weeks since prior prednisone

Radiotherapy

• See Disease Characteristics
• More than 3 weeks since prior radiotherapy for cancer
• More than 6 months since prior radioimmunotherapy for lymphoma

Surgery

• More than 4 weeks since prior major surgery (except diagnostic surgery)

Other

• Recovered from prior therapy
• More than 3 weeks since other prior immunosuppressive therapy
• Prior investigational drugs allowed