Zevalin and Velcade in Relapsed/Refractory Mantle Cell Lymphoma

The purpose of this study is to evaluate the effects (good and bad) of the combination of ibritumomab tiuxetan (Zevalin) and bortezomib (Velcade) in patients with relapsed/refractory mantle cell lymphoma.

Zevalin is a monoclonal antibody that is combined with a radioactive substance and given with another monoclonal antibody called rituximab (Rituxan). It works by attaching to cancer cells and releasing radiation to damage those cells. Both Zevalin and Rituxan are given in this study, along with Velcade.

This is a non-randomized, unblinded single arm Phase II trial to evaluate the combination of yttrium90 ibritumomab tiuxetan and bortezomib in patients with relapsed/refractory mantle cell lymphoma (MCL). Standard hematology and chemistries, imaging and bone marrow biopsies will be done.

Research tests: 17cc of blood will be collected at screen, Day 8 OR 11 and month 3. Samples will be collected and stored for future analysis. These analyses may include but are not limited to measurements of proteasome inhibition. No genetic studies will be performed on these samples. Samples will be destroyed at the end of the study.

Primary Objective Estimate the overall response rate (CR + PR) of the combination of bortezomib and ibritumomab tiuxetan in patients with relapsed/refractory mantle cell lymphoma.

Secondary Objectives

* Estimate the progression free and overall survival in patients with relapsed/refractory mantle cell lymphoma who receive bortezomib and ibritumomab tiuxetan.
* Assess the toxicity of the combination of bortezomib and ibritumomab tiuxetan in patients with relapsed/refractory MCL.

Eligibility Criteria:
Inclusion Criteria:

* Patients with relapsed or refractory Mantle Cell lymphoma with measurable disease.
* Age \> 18 years old
* Expected survival \>/= 3 months
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 at initiation of study (Appendix I).
* Laboratory tests meet the levels specified in the protocol

Exclusion Criteria:

* Patients must not have received chemotherapy, radiation or surgical resection of malignancy within 3 weeks of study initiation. However, if they have received nitrosurea or mitomycin C then they should not be enrolled in the study until 6 weeks after therapy was last received.
* No limitations to number of prior therapies
* No prior radioimmunotherapy (RIT)
* Prior bortezomib is allowed
* Patient must be fully recovered from all toxicities associated with prior surgery, radiation treatment, chemotherapy or immunotherapy.
* No active, serious infection or medical or psychiatric illness likely to interfere with participation in this clinic trial
* No known HIV infection
* No active central nervous system (CNS) involvement
* Bone Marrow Involvement \>/= 25% within 30 days of initiation of study treatment
* Pregnant or breast feeding
* No patients who have received Granulocyte colony-stimulating factor (G-CSF) or Granulocyte macrophage colony-stimulating factor (GM-CSF) within the 14 days prior to initiating protocol
* No patient who has had major surgery within the four weeks prior to initiating protocol therapy
* No patients with pleural effusion or significant ascites