| Inclusion Criteria: | 1) For part 1 and part 2 (arms 1 and 2):subjects who have been previously diagnosed with CD20 and CD22-positive, follicular or diffuse large B-cell NHL, according to WHO classification, which has not responded to or progressed after 1 or 2 prior therapies of probable clinical benefit.
2) For arm 3: subjects with CD20 and CD22-positive intermediate/aggressive NHL (diffuse large b-cell, mantle cell lymphoma, transformed follicular lymphoma or grade 3b follicular lymphoma), according to WHO classification, which has not responded or progressed after 1 or more therapies of probable clinical benefit.Prior CD20 and CD22-immunophenotyping of tumors to document B-cell NHL is acceptable.
3) continuation # 2) If such prior documentation is not available, then the immunophenotype of the current disease must be documented by fine-needle aspirate or biopsy, or by circulating CD20 and CD22-positive NHL cells from peripheral blood during screening.
4) Prior therapy must contain at least one dose of rituximab therapy, as single agent or in combination. For part 1 and 2 (arms 1 and 2): subjects cannot be refractory to rituximab (refractory = PD under treatment or within 6 months of start of therapy, rituximab as single agent or in combination). For arm 3 of the expanded MTD cohort: only subjects who are refractory to a previous rituximab containing chemotherapy regimen will be enrolled.
5) continuation #4) Refractory for this group is defined as having exhibited no response (CR or PR) to the most recent rituximab containing therapy, or have relapsed within 6 months of the first dose of the rituximab containing induction therapy. The induction phase of the previous rituximab containing regimen must have included at least 2 cycles of treatment.
6) Age 18 years or older.
7) Eastern Cooperative Oncology Group (ECOG) performance status </= 2
8) Life expectancy >/= 12 weeks.
9) ANC >/= 1.5 x 10^9/L (1,500/microL) and platelets >/= 75 x 10^9/L (75,000/microL)
10) Serum creatinine </= 1.5 x the upper limit of normal (ULN) and urine protein to creatinine ratio of </= 0.2.
11) Total bilirubin </= 1.5 x ULN, aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) </= 2.5 x ULN.
12) Measurable disease with a lymph node or tumor mass >/= 1.5 cm x 1.5 cm by CT at inclusion, in an area of no prior radiation therapy, or clear progression in an area that was previously irradiated.
13) Willingness of male and female subjects who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control during the active part of the study, including 12 months after the last dose of test article. Sexually active males and females using oral contraceptive pills should also use barrier contraception.
14) Negative serum pregnancy test within 1 week before first treatment if the subject is a woman of childbearing potential. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives. |