A Study of SGN-40 in Combination With Rituximab in Patients With CD20-Positive, Follicular and Marginal Zone B-Cell Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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This is an open-label, multicenter Phase Ib study designed to evaluate the safety, pharmacokinetics, and preliminary efficacy of SGN-40 when combined with rituximab in patients with relapsed CD20-positive, follicular or marginal zone NHL who have received at least one prior rituximab-containing regimen.

Official Title
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An Open-Label, Phase Ib Study of the Safety, Pharmacokinetics, and Activity of the Anti-CD40 Monoclonal Antibody SGN-40 Administered in Combination With Rituximab in Patients With CD20-Positive, Follicular and Marginal Zone B-Cell Non-Hodgkin's Lymphoma Who Have Relapsed Following Previous Rituximab Therapy

Conditions
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Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: rituximab
* Drug: SGN-40


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented history of histologically confirmed CD20-positive, follicular NHL or marginal zone NHL At least one previous treatment with rituxan monotherapy or a rituximab-containing regimen Measurable disease Either fresh or archived tumor specimen must be available for central confirmation of diagnosis and correlative studies Life expectancy of > 3 months For patients of reproductive potential, use of a reliable means of contraception Exclusion Criteria: Chemotherapy or radiotherapy within 28 days of Day 1 Prior treatment with a monoclonal antibody directed against CD40 Radioimmunotherapy or immunotherapy with a monoclonal antibody other than rituximab within 3 months of Day 1 Prior treatment with an investigational drug within 28 days of Day 1 Prior allogeneic bone marrow transplant Prior autologous hematopoietic stem cell transplant within 12 weeks of Day 1 Concurrent systemic corticosteroid therapy Prior anaphylactoid or other serious reaction to rituximab that resulted in hospitalization or discontinuation of therapy, or both Evidence of clinically detectable ascites on Day 1 Other invasive malignancies within 3 years prior to Day 1 except for adequately treated basal cell or squamous cell skin cancer, in situ carcinoma of the cervix, in situ breast cancer, in situ prostate cancer, or other cancer of which the patient has been disease-free for at least 3 years History or evidence on physical examination of CNS disease Active infection requiring parenteral antibiotics within 14 days of Day 1 Major surgical procedure (excluding lymph node biopsy) or significant traumatic injury within 28 days prior to Day 1 Pregnancy (positive pregnancy test) or lactation Serious, nonhealing wound, ulcer, or bone fracture Clinically significant cardiovascular disease, congestive heart failure, serious cardiac arrhythmia requiring medication within 1 year prior to Day 1. Grade II or greater peripheral vascular disease at study entry. Known human immunodeficiency virus (HIV) infection Known serious medical conditions, including cirrhosis, hepatitis C infection, and chronic obstructive or chronic restrictive pulmonary disease

Ages Eligible for Study
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Minimum Age: 18 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: rituximab<br>* Escalating intravenous repeating dose<br>Drug: SGN-40<br>* Escalating intravenous repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and nature of dose-limiting toxicities in order to determine the maximum tolerated dose |  | Length of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in vital signs, physical examination findings, and clinical laboratory results |  | Length of study | 
| Incidence, nature, and severity of adverse events |  | Length of study | 
| Pharmacokinetic parameters |  | Length of study | 
| Patient's best response as assessed by the investigator |  | Length of study | 
| Duration of response |  | Length of study | 
| Event-free survival |  | Length of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NHL, Rituxan, anti-CD40