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

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Biological therapies such as CpG 7909 use different ways to stimulate the immune system and stop cancer cells from growing. Combining CpG 7909 with rituximab may kill more cancer cells. PURPOSE: Phase I trial to study the effectiveness of CpG 7909 plus rituximab in treating patients who have relapsed or refractory non-Hodgkin's lymphoma.

Detailed Description
-----------------
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.

Official Title
-----------------
A Multi-Center, Phase I, Open Label, Two Arm, Non-Randomized, Dose-Escalation, Study Of The Safety And Tolerability Of CPG 7909 In Patients Receiving Rituxan For Relapsed Or Refractory B-Cell Non-Hodgkin's Lymphoma

Conditions
-----------------
Lymphoma

Intervention / Treatment
-----------------
* Biological: rituximab
* Drug: agatolimod sodium


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: rituximab|nan|
|Drug: agatolimod sodium|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult Burkitt lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma