Bortezomib and Vorinostat in Treating Patients With Recurrent Mantle Cell Lymphoma or Recurrent and/or Refractory Diffuse Large B-Cell Lymphoma

• Status: Completed
• Trial end date: 2017-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Bortezomib; Vorinostat

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