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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00703664
First received: June 20, 2008
Last updated: October 2, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Mantle Cell Lymphoma
Drug: vorinostat
Drug: bortezomib
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Bortezomib and Vorinostat in Mantle Cell and Diffuse Large B-Cell Lymphomas

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rates (complete and partial response) assessed according to the Revised Response Criteria for Malignant Lymphoma [ Time Frame: Up to 9 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 116
Study Start Date: July 2008
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (vorinostat, bortezomib)
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.
Drug: vorinostat
Given PO
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Other: laboratory biomarker analysis
Correlative studies

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00703664

Locations
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Northwestern University
Chicago, Illinois, United States, 60611
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
Albert Einstein College of Medicine
Bronx, New York, United States, 10461
Montefiore Medical Center - Moses Campus
Bronx, New York, United States, 10467-2490
Weill Medical College of Cornell University
New York, New York, United States, 10065
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Investigators
Principal Investigator: Beata Holkova Moffitt Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00703664     History of Changes
Other Study ID Numbers: NCI-2009-00275, NCI-2009-00275, CDR0000598308, MCC-8064, 8064, N01CM00071, N01CM00100, P30CA076292, N01CM62201, N01CM62208, N01CM62204
Study First Received: June 20, 2008
Last Updated: October 2, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 21, 2014