| Exclusion Criteria: | 1) Prior radiotherapy to a measurable, metastatic lesion(s) to be used to measure response unless that lesion shows unequivocal progression at baseline.
2) 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.
3) Chemotherapy, hormonal therapy, radiotherapy, or immunotherapy within 4 weeks prior to Day 1 (6 weeks for nitrosoureas or mitomycin).
4) Subjects 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 Cycle 1, Day 1, have adequate bone marrow function (as defined by minimal hemoglobin, ANC, and platelet count requirements), and have no evidence of myelodysplastic syndrome on bone marrow aspirate/biopsy.(as evidenced by cytogenetic or fluorescence in situ hybridization criteria)
5) Prior treatment with Apo2L/TRAIL or an agonist antibody to DR4 or DR5.
6) Concurrent systemic corticosteroid therapy (except low-dose corticosteroid therapy used to treat an illness other than lymphoma or single administrations of hydrocortisone up to 100mg/dose, prior to rituximab infusions for prophylaxis against severe infusion reaction).
7) Evidence of clinically detectable ascites on Day 1. (Small pleural and peritoneal effusions detected incidentally on screening CT scans are not exclusionary).
8) Other invasive malignancies within 3 years prior to first study drug administration except for adequately treated (with curative intent) basal or squamous cell skin cancer, in situ carcinoma of the cervix, in situ breast cancer, in situ prostate cancer, limited-stage bladder cancer, or other cancers from which the subject has been disease free for at least 3 years.
9) History or evidence upon physical examination of CNS disease (e.g., primary brain tumor, seizures not controlled with standard medical therapy, any brain metastasis, or history of stroke) within 1 year prior to study entry.
10) Active infection requiring parenteral antibiotics on Day 1.
11) Major surgical proceudre, 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.
12) Pregnancy or lactation.
13) Serious nonhealing wound, ulcer, or bone fracture.
14) Current or recent (within the 28 days prior to Day 1) participation in another experimental drug study.
15) Clinically significant cardiovascular disease (e.g., uncontrolled hypertension with BP > 140/90, myocardial infarction, unstable angina), New York Heart Association (NYHA) Grade II or greater congestive heart failure, serious ventricular cardiac arrhythmia requiring medication within 1 year prior to Day 1, Grade II or greater peripheral vascular disease on Day 1.
16) Clinical laboratory values: ANC < 1500 microL, Platelet count < 75,000 microL, Hemoglobin < 9 g/dL (may not be transfused or treated with erythropoietin to maintain or exceed this level), Total bilirubin > 1.6 mg/dL, AST or ALT > 2.5 times the upper limit of normal, Serum creatinine > 2.0 mg/dL or measured creatinine clearance < 50 mLs/min.
17) Known positive test result for HIV, hepatitis B surface antigen (sAg), hepatitis B IgG and immunoglobulin M (IgM) core antibody, or hepatitis C antibody.
18) 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.
19) Known sensitivity to murine or human antibodies. |