Bortezomib and Vorinostat in Treating Patients With Recurrent Mantle Cell Lymphoma or Recurrent and/or Refractory Diffuse Large B-Cell Lymphoma
Phase II Trial of Bortezomib and Vorinostat in Mantle Cell and Diffuse Large B-Cell Lymphomas
10 other identifiers
interventional
65
1 country
12
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jul 2008
Longer than P75 for phase_2
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 20, 2008
CompletedFirst Posted
Study publicly available on registry
June 23, 2008
CompletedStudy Start
First participant enrolled
July 9, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2017
CompletedResults Posted
Study results publicly available
August 7, 2018
CompletedAugust 7, 2018
July 1, 2018
9.4 years
June 20, 2008
June 15, 2018
July 11, 2018
Conditions
Outcome Measures
Primary Outcomes (1)
Overall Response Rate (ORR)
ORR: Complete Response (CR) + Partial Response (PR) assessed according to the Revised Response Criteria for Malignant Lymphoma.
Up to 9 years
Secondary Outcomes (4)
Best Response
Up to 9 years
Progression-free Survival (PFS)
Up to 9 years
Duration of Partial Response
Up to 9 years
Duration of Stable Disease
Up to 9 years
Study Arms (1)
Treatment (vorinostat, bortezomib)
EXPERIMENTALParticipants 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.
Interventions
Bortezomib: 1.3 mg/m\^2/d IV days 1, 4, 8, and 11.
Vorinostat: 400 mg (total daily dose as a single dose) days 1-5 and 8-12.
Eligibility Criteria
You may qualify if:
- 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
- +11 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (12)
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Weill Medical College of Cornell University
New York, New York, 10065, United States
Montefiore Medical Center-Weiler Hospital
The Bronx, New York, 10461, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Cohort C met the 1st-stage efficacy endpoint to proceed to the 2nd stage but was closed with evidence that the 2nd-stage efficacy endpoint could not be achieved.
Results Point of Contact
- Title
- Dr. Beata Holkova
- Organization
- Massey Cancer Center, Virginia Commonwealth University
Study Officials
- PRINCIPAL INVESTIGATOR
Beata Holkova
Massey Cancer Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 20, 2008
First Posted
June 23, 2008
Study Start
July 9, 2008
Primary Completion
December 1, 2017
Study Completion
December 1, 2017
Last Updated
August 7, 2018
Results First Posted
August 7, 2018
Record last verified: 2018-07