Study of Veltuzumab and 90Y-Epratuzumab in Relapsed/Refractory, Aggressive NHL

Inclusion Criteria:

* Male or female, \>18 years old
* Histological diagnosis of CD20+ B-cell NHL, with DLBCL or other aggressive lymphomas by WHO lymphoma criteria including mantle cell lymphoma and transformed follicular lymphoma.
* Failed at least one prior standard treatment regimen for NHL
* If DLBCL, either received, ineligible for or refused high-dose chemotherapy with stem cell transplant
* Measurable NHL disease by CT, with at least one lesion \>1.5 cm in one dimension
* Adequate performance status (\>70 Karnofsky scale, 0-1 ECOG)\* with an estimated life expectancy of at least 6 months
* Laboratory parameters:

  * Adequate hematology (Hemoglobin \>/= 10 g/dL, ANC \>/= 1.5 ´ 109/L, platelets \>/=100 x 109/L) without ongoing transfusional support
  * Adequate renal and liver function (creatinine and bilirubin \</= 1.5 x IULN; AST and ALT \</= 2.5 x IULN)
* Otherwise, \<Grade 1 toxicity at study entry by NCI CTC version 3.0.
* 3 months beyond any prior rituximab or veltuzumab treatment, 12 weeks beyond autologous stem cell transplant and 4 weeks beyond chemotherapy, other experimental treatments, or any radiation therapy to the index lesion(s).
* Screened for hepatitis B (no time limit) and negative by tests included in NCCN guidelines (hepatitis B surface antigen/antibodies, core antigen/antibodies, hepatitis B e-antigen).
* Patients of childbearing potential must be willing to practice birth control during the study until at least 12 weeks after last veltuzumab infusion; women of childbearing potential must have a negative urine or serum pregnancy test to enter the study.
* Ability to provide signed, informed consent

Exclusion Criteria:

* Pregnant or lactating women. Women of childbearing potential are required to have a negative pregnancy test

  * NCI CTC Grade 3 or 4 infusion reaction to prior anti-CD20 antibodies (rituximab, veltuzumab, etc.)
  * A known anti-antibody response to prior antiCD20 antibodies (HACA positive, HAHA positive, etc)
  * Prior radioimmunotherapy, including Zevalin or Bexxar.
  * Prior high-dose chemotherapy with peripheral blood stem cell transplant.
  * Prior therapy with other human or humanized monoclonal antibodies, unless HAHA tested and negative
  * Primary CNS lymphoma, HIV lymphoma or transformed lymphoma, or presence of symptomatic CNS metastases or carcinomatous meningitis.
  * Rituximab or veltuzumab resistant, defined as having progressed during or within 6 months of any prior rituximab or veltuzumab treatment.
  * Bulky disease by CT, defined as any single mass \>10 cm in its greatest diameter
  * Bone marrow involvement ≥25%
  * Prior external beam radiation therapy to \>30% bone marrow.
  * Pleural effusion with positive cytology for lymphoma
  * Patients known to be HIV positive, hepatitis B positive, or hepatitis C positive
  * Known autoimmune disease or presence of autoimmune phenomena.
  * Evidence of infection or requiring antibiotics within 7 days.
  * Use of systemic corticosteroids within 2 weeks, except low dose regimens (prednisone, \<20 mg/day, or equivalent) which may continue if unchanged.
  * Prior malignancies (other than non-melanoma skin cancer or carcinoma in situ of the cervix) unless disease free for 5 years.
  * Prior malignancy with less than a 5-year disease-free interval, excluding nonmelanoma skin cancers and carcinoma in situ of the cervix.
  * Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations