This trial is active, not recruiting.

Conditions recurrent adult diffuse large cell lymphoma, recurrent mantle cell lymphoma
Treatments bortezomib, laboratory biomarker analysis, vorinostat
Phase phase 2
Targets HDAC, proteasome
Sponsor National Cancer Institute (NCI)
Start date July 2008
End date June 2017
Trial size 116 participants
Trial identifier NCT00703664, 8064, CDR0000598308, MCC-8064, N01CM00071, N01CM00100, N01CM62201, N01CM62204, N01CM62208, NCI-2009-00275, P30CA076292


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Patients receive vorinostat PO QD on days 1-5 and 8-12. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 3 weeks in the absence of disease progression- or unacceptable toxicity.
bortezomib [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid
Given IV
laboratory biomarker analysis
Correlative studies
vorinostat L-001079038
Given PO

Primary Outcomes

Response rates (complete and partial response) assessed according to the Revised Response Criteria for Malignant Lymphoma
time frame: Up to 9 years

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title Phase II Trial of Bortezomib and Vorinostat in Mantle Cell and Diffuse Large B-Cell Lymphomas
Principal investigator Beata Holkova
Description PRIMARY OBJECTIVES: I. Estimate the response rates of mantle cell and diffuse large B-cell lymphomas to bortezomib and vorinostat combination therapy. SECONDARY OBJECTIVES: I. Assess the safety and tolerability of the study regimen. II. Observe progression-free survival and response durations. III. Observe the relationship between pretreatment lymphoma cell nuclear v-rel reticuloendotheliosis viral oncogene homolog A (relA) and response. OUTLINE: Patients receive vorinostat orally (PO) once daily (QD) on days 1-5 and 8-12. Patients also receive bortezomib intravenously (IV) over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).