| Inclusion Criteria: | 1) Patient has pathologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL), including both de novo and transformed DLBCL and follicular lymphoma, Grade 3b (FL3b).a) local pathology review is acceptable for determining eligibility; b) prior therapy for indolent lymphoma is not allowed; c) for patients who have achieved a CR to first-line therapy, a repeat biopsy since relapse for confirmation of disease is required unless all of the following conditions are met:
2) Continuation from #1) Relapse has occurred within 1 year of completing first-line therapy; In the investigator's opinion, the CT and PET imaging and clinical presentation are consistent with relapsed DLBCL or FL3b; It is medically unsafe or infeasible to perform a biopsy due to the anatomic location of the tumor(s);The site has confirmed that there is adequate tissue from the initial diagnostic biopsy for central review to confirm diagnosis and perform all immunohistochemical and pharmacogenomic studies.
3) Patient has received at least four cycles of first-line therapy with R-CHOP or equivalent first-line therapy including rituximab, cyclophosphamide, anthracycline or anthracenedione, and steroid with or without additional chemotherapy agent(s). For patients who acheive CR with first-line therapy, maintenance rituximab prior to relapse is allowed.
4) Patient achieved a response of stable disease, partial response, or complete response following the last cycle of R-CHOP.
5) Patient currently has at least one site of measurable disease meeting both of the following criteria: Bidimensional measurement with longest axis greater than or equal to 1.5 cm by radiographic imaging. Positive FDG-PET scan at baseline.
6) A fresh or archived tumor specimen is available for central review to confirm diagnosis, assess expression levels of CD40 and other B cell surface markers ( e.g., Bcl-6, CD10, CD20) on malignant tumor cells, perform immunohistochemical studies to determine DLBCL subtype and/or for gene expression profiling by cDNA microarray analysis.
7) Patient has completed first-line therapy at least four weeks prior to the date of randomization.
8) Patient has an Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
9) Patient is at least 18 years old and no more than 75 years old.
10) Patient has the following required baseline laboratory data (eligibility can be based on local lab results): Platelet count greater than or equal to 75,000/mm^3. Absolute neutrophil count (ANC) greater than or equal to 1,000/mm^3 (may be maintained by growth factors). Alanine aminotransferase (ALT) and asparate aminotransferase (AST) less than or equal to 2.5 times upper limit of normal (ULN). Total serum bilirubin level less than or equal to 1.5 times ULN. Serum creatinine less than or equal to 1.5 times ULN.
11) If a female of childbearing potential, the patient has a negative serum or urine pregnancy test result (sensitivity at least 50 mlU/mL) within three days prior to the first dose of Investigational Drug or on Day -2, prior to first dose. ( Females of non-childbearing potential are those who are postmenopausal greater than one year or who have had a bilateral tubal ligation or hysterectomy).
12) If female of childbearing potential or a male patient, patient agrees to use an effective contraceptive method from the time of informed consent, during the course of the study, and for six months following the last dose of Investigational Drug.
13) Patient is available for periodic blood sampling, study-related assessments, and management of toxicity at the treating institution.
14) Patient or legally authorized representative understands and voluntarily signs the written informed consent prior to any study-specific procedures. A copy of the signed informed consent form will be retained by the treating institution. |