Effect of Rituximab on Immunological Recall Response to Specific Antigens in the Treatment of Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to provide treatment for patients who have relapsed Non-Hodgkin's lymphoma (NHL) or refractory NHL, and to test the immunity of study subjects after receiving four treatments with rituximab.

Official Title
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A Multicenter Study to Evaluate the Effect of Rituximab (IDEC-102) on Primary Humoral Response, Recall Response, and Maintenance of Acquired Immunity to Specific Antigens

Conditions
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Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed IRB-approved informed consent. Age >/=40 years. Men and women of reproductive potential who are following accepted birth control methods. Histologic confirmation of low-grade or follicular, B-cell NHL prior to study entry. Relapsed (maximum of 5 relapses) or refractory, low-grade or follicular, CD20+,B-cell NHL. WHO performance status </= 2. Expected survival >/= 1 year. Acceptable hematologic status, liver function, renal function, and pulmonary function. Patients must be recovered from all nonhematological toxicities associated with prior surgery, radiation treatments, chemotherapy, biological therapy, bone marrow transplant, investigational drugs, or immunotherapy. Known history of tetanus toxoid immunization or positive tetanus titer at the screening visit. Exclusion Criteria: Active autoimmune disease. Exposure to rituximab within 12 months prior to Day 1. Chemotherapy within 3 months prior to Day 1. Previous immunization with tetanus toxoid within 2 years prior to Day 1. Previous exposure to KLH. Receipt of intravenous or intramuscular immunoglobulin (IVIG or IMIG) within 30 days of Day 1. Known history of hepatitis or other hepatic disease, HIV infection, or AIDS. Current use (including recreational use) of any illicit drugs or history of drug or alcohol abuse within the 5 years prior to Day 1. Prior diagnosis of aggressive NHL or mantle-cell lymphoma. Chronic lymphocytic leukemia (CLL). Small lymphocytic lymphoma (IWF A) with peripheral blood lymphocyte count > 5,000 cells/mm3. History of other primary malignancy, with the exception of squamous cell carcinoma or basal cell carcinoma of the skin, in situ carcinoma of the cervix, or treated prostate cancer for which the subject has not been disease free for at least 3 years. Serious nonmalignant disease (e.g., congestive heart failure, hydronephrosis); active, uncontrolled bacterial, viral, or fungal infection; or any other condition that would compromise protocol objectives in the opinion of the investigator and/or sponsor. Known allergies or contraindications to tetanus toxoid or KLH. Known allergy to shellfish. Presence of protein-losing enteropathy. Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1. Participation in another clinical study with an investigational agent or device within the last year. The subject cannot participate in any other clinical study with an investigational agent or device during the course of this study. Pregnant or lactating female subjects

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Rituximab | Drug: rituximab<br>* Dose, schedule,and duration specified in protocol<br>|
| No Intervention: 2<br>No drug | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine whether treatment with rituximab causes a clinically significant effect on immunological recall response to tetanus vaccine in NHL patients |  | 8.5 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine whether NHL patients can mount a primary response to KLH after treatment with rituximab |  | 8.5 months after treatment | 
| To determine whether NHL subjects treated with rituximab experience clinically significant changes in antibody titers to a panel of specific antigens |  | 8.5 months after treatment |