None listed
Conditions
Brief summary
This Phase Ib/II, open-label, multicenter trial is designed to evaluate the safety, pharmacokinetics, and efficacy of Apo2L/TRAIL when combined with rituximab in subjects with follicular, CD20+, B-cell 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.
Interventions
Subjects will recieve Rituximab administered by IV infusion at 375 mg/m2 weekly for up to eight doses. Subjects randomized to the combination arm will also receive a maximum of four 21-day 8.0 mg/kg/day cycles of Apo2L/TRAIL (recombinant human Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand), by IV infusion.
Sponsors
Genentech
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Signed Informed Consent Form Age = 18 years History of histologically confirmed CD20+ follicular Non-Hodgkin's Lymphoma 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 Apo2L/TRAIL 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 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
Outcome results
None listed