Biological Therapy Plus Monoclonal Antibody Therapy in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

OBJECTIVES:

• Determine the maximum tolerated dose of subcutaneous and IV CpG 7909 when administered with rituximab in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.
• Determine the safety and tolerability of this regimen in these patients.
• Determine the disease response in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of CpG 7909. Patients are sequentially assigned to 1 of 2 treatment groups.

• Group A: Patients receive rituximab IV over 4-5 hours followed by CpG 7909 IV over 2 hours on day 1. Courses repeat weekly for 4 weeks.
• Group B: Patients receive rituximab as above followed by CpG 7909 subcutaneously on day 1. Courses repeat weekly for 4 weeks.

Cohorts of 3-6 patients receive escalating doses of CpG 7909 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 4 weeks.

PROJECTED ACCRUAL: A total of 6-48 patients (3-24 per treatment group) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed CD20+ B-cell non-Hodgkin's lymphoma (NHL)

• CD20 positive by immunohistochemistry or flow cytometry
• Relapsed or refractory disease
• Bidimensionally measurable disease

• Sole site of measurable disease within a previously irradiated field allowed provided there was disease progression at that site
• No pre-existing ascites or pleural effusions
• No known CNS involvement by NHL

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• More than 3 months

Hematopoietic:

• Neutrophil count at least 1,000/mm3
• Platelet count at least 50,000/mm3

Hepatic:

• Bilirubin less than 2 mg/dL
• Transaminase less than 2 times upper limit of normal
• No hepatitis B or C

Renal:

• Creatinine less than 2 mg/dL

Cardiovascular:

• No significant cardiovascular disease
• No New York Heart Association class III congestive heart failure
• No myocardial infarction within the past 6 months
• No unstable angina
• No uncontrolled atrial or ventricular cardiac arrhythmias

Pulmonary:

• No concurrent significant pulmonary disease

Other:

• HIV negative
• No acute infection requiring antibiotics
• No fever over 38.2 degrees C within the past 3 days
• No other malignancy within the past 5 years except basal cell or noninvasive squamous cell skin cancer or carcinoma in situ of the cervix
• No pre-existing autoimmune disease or antibody-mediated disease, including:

• Systemic lupus erythematosus
• Rheumatoid arthritis
• Multiple sclerosis
• Sjogren's syndrome
• Autoimmune thrombocytopenia
• Controlled thyroid disease allowed
• Concurrent autoantibodies without clinical autoimmune disease allowed
• No history of allergic reactions attributed to compounds of similar composition to study drugs
• No other medical history, including laboratory results, that would preclude study
• No suspected or confirmed poor compliance or mental instability that would preclude study
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior allogeneic transplantation
• More than 30 days since prior hematopoietic growth factors (e.g., filgrastim (G-CSF) or epoetin alfa)
• More than 30 days since prior immunotherapy
• More than 90 days since prior monoclonal antibodies as monotherapy for patients who were unresponsive to treatment (30 days for patients who responded to treatment and subsequently relapsed)
• No other concurrent biological agents
• No concurrent hematopoietic growth factors (e.g., G-CSF or epoetin alfa)

Chemotherapy:

• More than 30 days since prior chemotherapy
• No concurrent chemotherapy

Endocrine therapy:

• More than 30 days since prior systemic corticosteroids
• No concurrent systemic corticosteroids

Radiotherapy:

• See Disease Characteristics
• More than 30 days since prior radiotherapy
• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• Recovered from prior therapy
• At least 6 months since prior coronary angioplasty
• More than 30 days since prior immunosuppressants
• More than 30 days since prior participation in an investigational drug study
• No concurrent immunosuppressants
• No concurrent anticoagulants except aspirin at doses no greater than 325 mg/day
• No other concurrent anticancer therapy
• No other concurrent investigational agents