A Study of Dulanermin in Combination With Rituximab in Subjects With Follicular and Other Low Grade, CD20+, Non-Hodgkin's Lymphomas

A Phase Ib/II, Open-Label, Multicenter Study of the Safety, Pharmacokinetics, and Efficacy of Dulanermin Administered Intravenously in Combination With Rituximab to Subjects With Follicular and Other Low-Grade, CD20+, B-Cell Non-Hodgkin's Lymphomas That Have Progressed Following Previous Rituximab Therapy

This Phase Ib/II, open-label, multicenter trial is designed to evaluate the safety, pharmacokinetics, and efficacy of dulanermin when combined with rituximab in subjects with follicular, CD20+, B-cell Non-Hodgkin's Lymphoma (NHL) that has progressed following a response of ≥ 6 months duration to a prior rituximab-containing therapy. The multicenter, international, randomized Phase II part of this study will commence only after the safety and available pharmacokinetic data from the Phase Ib part of the study have been evaluated by the Sponsor and have been provided to participating investigators and the FDA.

Inclusion Criteria:

• Signed Informed Consent Form
• Age ≥ 18 years
• History of histologically confirmed CD20+ follicular NHL Grade 1, 2, or 3a
• Progression of disease following the most recent treatment with rituximab-containing therapy that resulted in stable disease or a partial or complete response lasting ≥ 6 months
• Measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• For subjects of reproductive potential (males and females), use of a reliable means of contraception (e.g., contraceptive pill, intrauterine device [IUD], physical barrier throughout the trial and for 1 year following their final exposure to study treatment).
• Life expectancy of > 3 months

Exclusion Criteria:

• Prior radiotherapy to a measurable, metastatic lesion(s) to be used to measure response unless that lesion shows unequivocal progression at baseline
• Radiation therapy to a peripheral lesion within 14 days prior to Day 1; Radiation therapy to a thoracic, abdominal, or pelvic field within 28 days prior to Day 1
• Chemotherapy, hormonal therapy, radiotherapy, or immunotherapy within 4 weeks prior to Day 1
• Patients who have received radioimmunotherapy for relapsed or refractory, follicular NHL are eligible for the study if they received this therapy at least 1 year prior to Day 1, they have adequate bone marrow function, and they have no evidence of myelodysplastic syndrome on bone marrow aspirate/biopsy
• Prior treatment with dulanermin or an agonist antibody to DR4 or DR5
• Concurrent systemic corticosteroid therapy
• Evidence of clinically detectable ascites on Day 1
• Other invasive malignancies within 5 years prior to Day 1
• History or evidence upon physical examination of central nervous system (CNS) disease within 1 year prior to study entry
• Active infection requiring parenteral antibiotics on Day 1
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study and fine needle aspirations within 7 days prior to Day 1
• Pregnancy or lactation
• Serious nonhealing wound, ulcer, or bone fracture
• Current or recent participation in another experimental drug study
• Clinically significant cardiovascular disease
• Known positive test result for HIV, hepatitis B surface antigen (sAg), hepatitis B IgG or IgM core antibody, or hepatitis C antibody
• Known sensitivity to murine or human antibodies
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk from treatment complications