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

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

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.

Study Overview

• Status: Completed
• Conditions: Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: SGN-40; Drug: rituximab

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: SGN-40; Escalating intravenous repeating dose; Drug: rituximab; Escalating intravenous repeating dose

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Collaborators: Seagen Inc.
• Investigators: Study Director: Deborah Hurst, M.D., Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: November 9, 2007
• First Submitted That Met QC Criteria: November 9, 2007
• First Posted (Estimate): November 12, 2007

Study Record Updates

• Last Update Posted (Estimate): March 20, 2014
• Last Update Submitted That Met QC Criteria: March 18, 2014
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Keywords: Rituxan; NHL; anti-CD40
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: ACF4325g