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

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.
Brief Title
Bortezomib and Vorinostat in Treating Patients With Recurrent Mantle Cell Lymphoma or Recurrent and/or Refractory Diffuse Large B-Cell Lymphoma
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.
Completion Date
Completion Date Type
Actual
Conditions
Recurrent Mantle Cell Lymphoma
Recurrent Non-Hodgkin Lymphoma
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
Inclusion 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

Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT00703664
Org Class
Nih
Org Full Name
National Cancer Institute (NCI)
Org Study Id
NCI-2009-00275
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Phase II Trial of Bortezomib and Vorinostat in Mantle Cell and Diffuse Large B-Cell Lymphomas
Primary Outcomes
Outcome Description
ORR: Complete Response (CR) + Partial Response (PR) assessed according to the Revised Response Criteria for Malignant Lymphoma.
Outcome Measure
Overall Response Rate (ORR)
Outcome Time Frame
Up to 9 years
Secondary Ids
Secondary Id
NCI-2009-00275
Secondary Id
CDR0000598308
Secondary Id
MCC-15428
Secondary Id
8064
Secondary Id
N01CM00071
Secondary Id
N01CM00100
Secondary Id
N01CM62201
Secondary Id
N01CM62204
Secondary Id
N01CM62208
Secondary Id
P30CA076292
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Up to 9 years
Outcome Measure
Best Response
Outcome Description
Median progression-free survival in months per cohort.
Outcome Time Frame
Up to 9 years
Outcome Measure
Progression-free Survival (PFS)
Outcome Description
Median duration of response per cohort.
Outcome Time Frame
Up to 9 years
Outcome Measure
Duration of Partial Response
Outcome Description
Median duration of stable disease per cohort.
Outcome Time Frame
Up to 9 years
Outcome Measure
Duration of Stable Disease
Start Date
Start Date Type
Actual
Status Verified Date
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ioannis Mantzaris
Investigator Email
IMANTZAR@montefiore.org
Investigator Phone

Categories Mesh Debug
Cancer --- NEOPLASMS
Blood & Bone Marrow Cancers --- LYMPHOPROLIFERATIVE DISORDERS
Blood & Bone Marrow Cancers --- LYMPHATIC DISEASES
Blood & Bone Marrow Cancers --- IMMUNOPROLIFERATIVE DISORDERS
Infectious Disease --- IMMUNE SYSTEM DISEASES
Lung --- IMMUNE SYSTEM DISEASES
MeSH Terms
LYMPHOMA, MANTLE-CELL
LYMPHOMA, NON-HODGKIN
LYMPHOMA
NEOPLASMS BY HISTOLOGIC TYPE
NEOPLASMS
LYMPHOPROLIFERATIVE DISORDERS
LYMPHATIC DISEASES
HEMIC AND LYMPHATIC DISEASES
IMMUNOPROLIFERATIVE DISORDERS
IMMUNE SYSTEM DISEASES
BORTEZOMIB
VORINOSTAT
BORONIC ACIDS
ACIDS, NONCARBOXYLIC
ACIDS
INORGANIC CHEMICALS
BORON COMPOUNDS
ORGANIC CHEMICALS
PYRAZINES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
ANILIDES
AMIDES
ANILINE COMPOUNDS
AMINES
HYDROXAMIC ACIDS
HYDROXYLAMINES
HYDROXY ACIDS
CARBOXYLIC ACIDS