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

Recurrent Mantle Cell Lymphoma Clinical Trial

Official title:

Phase II Trial of Bortezomib and Vorinostat in Mantle Cell and Diffuse Large B-Cell Lymphomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00703664
• Other study ID #: NCI-2009-00275
• Secondary ID: NCI-2009-00275CD
• Status: Completed
• Phase: Phase 2
• Start date: July 9, 2008
• Est. completion date: December 1, 2017

Study information

• Verified date: July 2018
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: December 1, 2017
• Est. primary completion date: December 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Recurrent Mantle Cell Lymphoma
• Recurrent Non-Hodgkin Lymphoma

Intervention

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

Other:
• Laboratory Biomarker Analysis
Correlative studies

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

Locations

Country	Name	City	State
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
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	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Best Response	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.	Up to 9 years
Secondary	Progression-free Survival (PFS)	Median progression-free survival in months per cohort.	Up to 9 years
Secondary	Duration of Partial Response	Median duration of response per cohort.	Up to 9 years
Secondary	Duration of Stable Disease	Median duration of stable disease per cohort.	Up to 9 years