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

NCT ID: NCT00703664

Last Updated: 2018-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-09
• Study Completion Date: 2017-12-01

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.

Detailed Description

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

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.

Conditions

Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

Bortezomib: 1.3 mg/m\^2/d IV days 1, 4, 8, and 11.

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Vorinostat

Intervention Type: DRUG

Vorinostat: 400 mg (total daily dose as a single dose) days 1-5 and 8-12.

Interventions

Bortezomib

Bortezomib: 1.3 mg/m\^2/d IV days 1, 4, 8, and 11.

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Vorinostat

Vorinostat: 400 mg (total daily dose as a single dose) days 1-5 and 8-12.

Intervention Type: DRUG

Other Intervention 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; L-001079038; MSK-390; SAHA; Suberanilohydroxamic Acid; Suberoylanilide Hydroxamic Acid; Zolinza

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Beata Holkova

Role: PRINCIPAL_INVESTIGATOR

Massey Cancer Center

Locations

Moffitt Cancer Center

Tampa, Florida, United States

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Weill Medical College of Cornell University

New York, New York, United States

Montefiore Medical Center-Weiler Hospital

The Bronx, New York, United States

Montefiore Medical Center - Moses Campus

The Bronx, New York, United States

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2009-00275

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000598308

Identifier Type: -

Identifier Source: secondary_id

MCC-15428

Identifier Type: OTHER

Identifier Source: secondary_id

8064

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM00071

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM00100

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62201

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62204

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62208

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA076292

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00275

Identifier Type: -

Identifier Source: org_study_id