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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00703664
Recruitment Status : Completed
First Posted : June 23, 2008
Results First Posted : August 7, 2018
Last Update Posted : August 7, 2018
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief 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.

Condition or disease Intervention/treatment Phase
Recurrent Mantle Cell Lymphoma Recurrent Non-Hodgkin Lymphoma Drug: Bortezomib Other: Laboratory Biomarker Analysis Drug: Vorinostat Phase 2

Detailed Description:

This was a multicenter, non-randomized phase 2 trial using a Simon two-stage design with 3 cohorts.


I. Estimate the response rates of mantle cell and diffuse large B-cell lymphomas to bortezomib and vorinostat combination therapy.


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.


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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 65 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Bortezomib and Vorinostat in Mantle Cell and Diffuse Large B-Cell Lymphomas
Actual Study Start Date : July 9, 2008
Actual Primary Completion Date : December 1, 2017
Actual Study Completion Date : December 1, 2017

Arm Intervention/treatment
Experimental: Treatment (vorinostat, bortezomib)

Participants receive vorinostat orally (PO) once daily (QD) on days 1-5 and 8-12. Participants also receive bortezomib intravenously (IV) over 3-5 seconds on days 1, 4, 8, and 11. Vorinostat precedes bortezomib on days of concurrent administration. Courses repeat every 3 weeks in the absence of disease progression - or unacceptable toxicity. After completion of study therapy, participants are followed periodically.

Treatment arm consists of 3 cohorts, all receiving the same treatment:

A: Mantle Cell Lymphoma (MCL) - with no prior bortezomib.

B: Mantle Cell Lymphoma (MCL) - with no prior bortezomib.

C: Diffuse Large B-Cell Lymphoma (DLBCL) - with no prior bortezomib.

Drug: Bortezomib
Bortezomib: 1.3 mg/m^2/d IV days 1, 4, 8, and 11.
Other Names:
  • [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid
  • LDP 341
  • MLN341
  • PS-341
  • PS341
  • Velcade

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Vorinostat
Vorinostat: 400 mg (total daily dose as a single dose) days 1-5 and 8-12.
Other Names:
  • L-001079038
  • MSK-390
  • SAHA
  • Suberanilohydroxamic Acid
  • Suberoylanilide Hydroxamic Acid
  • Zolinza

Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: Up to 9 years ]
    ORR: Complete Response (CR) + Partial Response (PR) assessed according to the Revised Response Criteria for Malignant Lymphoma.

Secondary Outcome Measures :
  1. Best Response [ Time Frame: Up to 9 years ]
    Number of participants per category: Partial Response (PR), Stable Disease (SD), Progressive Disease (PD). PR: Regression of measurable disease and no new sites. SD: Failure to attain Complete Response (CR), /PR or PD. Relapsed or Progressive Disease: Any new lesion or increase by ≥ 50% of previously involved sites from nadir.

  2. Progression-free Survival (PFS) [ Time Frame: Up to 9 years ]
    Median progression-free survival in months per cohort.

  3. Duration of Partial Response [ Time Frame: Up to 9 years ]
    Median duration of response per cohort.

  4. Duration of Stable Disease [ Time Frame: Up to 9 years ]
    Median duration of stable disease per cohort.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00703664

United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
United States, Maryland
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201
United States, New Jersey
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903
United States, New York
Montefiore Medical Center-Weiler Hospital
Bronx, New York, United States, 10461
Montefiore Medical Center - Moses Campus
Bronx, New York, United States, 10467
Weill Medical College of Cornell University
New York, New York, United States, 10065
United States, North Carolina
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States, 27599
United States, Tennessee
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Virginia
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Beata Holkova Massey Cancer Center
  Study Documents (Full-Text)

Documents provided by National Cancer Institute (NCI):

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00703664     History of Changes
Other Study ID Numbers: NCI-2009-00275
NCI-2009-00275 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MCC-15428 ( Other Identifier: Moffitt Cancer Center )
8064 ( Other Identifier: CTEP )
N01CM00071 ( U.S. NIH Grant/Contract )
N01CM00100 ( U.S. NIH Grant/Contract )
N01CM62201 ( U.S. NIH Grant/Contract )
N01CM62204 ( U.S. NIH Grant/Contract )
N01CM62208 ( U.S. NIH Grant/Contract )
P30CA076292 ( U.S. NIH Grant/Contract )
First Posted: June 23, 2008    Key Record Dates
Results First Posted: August 7, 2018
Last Update Posted: August 7, 2018
Last Verified: July 2018

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action