Phase II Trial of Bortezomib and Vorinostat in Mantle Cell and Diffuse Large B-Cell Lymphomas

Inclusion Criteria:

- Histologically confirmed diagnosis of 1 of the following:

- Mantle cell lymphoma meeting the following criteria:

- Previously treated or untreated disease

- Diffuse large B-cell lymphoma (cohort 3) meeting the following criteria:

- At least 1 prior systemic therapy

- No prior bortezomib

- Measurable disease, defined as ≥ 1 lesion > 1.0 cm in diameter in both the long and
short axis, according to Revised Response Criteria for Malignant Lymphoma, as
measured by spiral CT scan or physical exam

- Must have histological material available for pathologic review and correlative
studies, including either of the following:

- Archival specimens from previous biopsies

- Specimens from repeat biopsy for histological confirmation in patients with
lymphoma that has undergone histological transformation in the past

- No history of brain metastasis, including leptomeningeal metastasis

- ECOG performance status 0-2

- Life expectancy > 3 months

- ANC ≥ 1.5 x 10^9/L

- CD4 count ≥ 0.5 x 10^9/L (must be specifically assayed only in patients with known
HIV infection)

- Platelet count ≥ 75 x 10^9/L

- Total bilirubin ≤ 2 mg/dL

- AST and ALT ≤ 2.5 times upper limit of normal

- Creatinine normal OR creatinine clearance ≥ 60 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception prior to and during study treatment

- Able to tolerate loperamide or other anti-diarrheal medications

- Able to take oral medications

- No neuropathy ≥ grade 2

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to bortezomib or vorinostat

- No medical or other condition (e.g., uncontrolled infection or potentially
life-threatening changes on EKG) that would represent an inappropriate risk to the
patient or likely would compromise achievement of the primary study objective

- Able to understand and willing to sign a written informed consent document

- No concurrent treatment (e.g., marrow suppressive agents such as zidovudine) that
would represent an inappropriate risk to the patient or likely would compromise
achievement of the primary study objective

- Recovered from prior treatment

- No prior histone deacetylase inhibitor as cancer treatment

- No prior bortezomib

- Prior allogeneic stem cell transplantation allowed provided that all of the following
conditions are met:

- At least 6 months since allogeneic transplantation

- No graft-vs-host disease is present

- Not currently on immunosuppressive therapy

- More than 3 weeks since prior chemotherapy or large field radiotherapy

- No plan for other concurrent cancer treatment; If steroids for cancer control have
been used, patients must be off these agents for ≥ 1 week before starting treatment.
Exception: maintenance therapy for non-malignant disease with prednisone or steroid
equivalent dose < 10 mg/day is permitted

- No concurrent investigational agent