Bortezomib and Vorinostat in Treating Patients With Recurrent Mantle Cell Lymphoma or Recurrent and/or Refractory Diffuse Large B-Cell Lymphoma
Condition: Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Recurrence
Intervention: Bortezomib; Laboratory Biomarker Analysis; Vorinostat
Intervention description: Bortezomib: 1.3 mg/m^2/d IV days 1, 4, 8, and 11.; Correlative studies; Vorinostat: 400 mg (total daily dose as a single dose) days 1-5 and 8-12.
Intervention MeSH terms: Bortezomib; Vorinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 65.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well bortezomib and vorinostat work in treating patients with
      recurrent mantle cell lymphoma or recurrent and/or refractory diffuse large B-cell lymphoma.
      Bortezomib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes
      needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed mantle cell or diffuse large B-cell lymphoma; histological
             material must be available for central pathological review; unstained histological
             material -- slides or blocks -- must be available for correlative studies; archived
             material from previous biopsies is acceptable, unless a patient's lymphoma has been
             known to undergo histological transformation in the past, in which case a repeat
             biopsy to confirm histology prior to enrollment is required; availability of material
             must be confirmed at the time of registration, but material may be submitted
             subsequent to registration and initiation of study treatment

          -  Measurable disease according to the Revised Response Criteria for Malignant Lymphoma;
             this requires at least one lesion greater than 1.0 cm in diameter in both the long and
             short axis as measured by spiral computed tomography (CT) scan or physical exam

          -  Prior allogeneic stem cell transplant is allowed provided that all of the following
             conditions are met:

               -  >= 6 months have elapsed since allogeneic transplant

               -  No graft vs. host disease (GVHD) is present

               -  Not currently on immunosuppressive therapy

          -  Prior therapy:

               -  Mantle cell lymphoma:

                    -  Previously treated or untreated

                    -  No prior bortezomib

               -  Diffuse large B-cell lymphoma:

                    -  At least one prior systemic therapy

                    -  No prior bortezomib

                         -  Note: Not intended for patients in first relapse who are candidates for
                            high dose therapy with stem cell support

          -  Life expectancy of greater than 3 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2

          -  Able to tolerate loperamide or other anti-diarrheal medications

          -  Absolute neutrophil count >= 1.5 x 10^9/L

          -  Platelets >= 75 x 10^9/L

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transferase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x institutional upper limit of normal

          -  Creatinine within normal institutional limits or calculated creatinine clearance >= 60
             mL/min according to the Cockcroft-Gault formula

          -  For patients with known human immunodeficiency virus (HIV) infection, a cluster of
             differentiation (CD)4 count >= 0.5 x 10^9/L

          -  For patients whose last treatment included bendamustine or fludarabine, a CD4 count >=
             0.4 x 10^9/L

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation and to report pregnancy or suspected pregnancy
             while participating in the study

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Chemotherapy or large field radiotherapy within 3 weeks prior to entering the study

          -  Prior histone deacetylase inhibitor as cancer treatment

          -  Concurrent treatment with other investigational agents

          -  Plans 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

          -  History of brain metastasis including leptomeningeal metastasis

          -  Grade >= 2 neuropathy, regardless of cause

          -  Unable to take oral medications

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to bortezomib or vorinostat

          -  Not sufficiently recovered from previous treatment

          -  Medical or other condition (for example: uncontrolled infection; potentially life
             threatening changes on electrocardiogram [EKG]) or concurrent treatment (for example,
             marrow suppressive agents such as zidovudine) that represents an inappropriate risk to
             the patient or likely would compromise achievement of the primary study objective;
             patients should be closely monitored when given bortezomib in combination with the
             cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors and inducers

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued

          -  Active concurrent malignancy, except adequately treated non-melanoma skin cancer