Ofatumumab and Bortezomib in Subjects With Relapsed Cluster of Differentiation Antigen 20 (CD20)+ Non-Hodgkin's Lymphoma (NHL)
This phase II trial studies how well giving ofatumumab together with bortezomib works in treating patients with relapsed diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), or mantle cell lymphoma (MCL). Monoclonal antibodies, such as ofatumumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving ofatumumab together with bortezomib may help kill more cancer cells
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Other: laboratory biomarker analysis
Other: enzyme-linked immunosorbent assay
Procedure: quality-of-life assessment
Genetic: polymorphism analysis
Other: flow cytometry
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of Ofatumumab and Bortezomib in Subjects With Relapsed Cluster of Differentiation Antigen 20 (CD20)+ Diffuse Large B Cell Lymphoma, Follicular Lymphoma, or Mantle Cell Lymphoma|
- Response rate of ofatumumab with bortezomib in patients with non-Hodgkin lymphoma, including DLBCL, MCL, and FL, who fail or are resistant to rituximab containing immunochemotherapy [ Time Frame: Every 2 courses during treatment and then every 3 months for 2 years ] [ Designated as safety issue: No ]Based on International Working Group(IWG) criteria, recorded in four categories: CR, PR, stable disease (SD) and progressive disease (PD). A response is defined to be either CR/PR. A failure in response includes SD/PD.
- Overall Survival [ Time Frame: Up to every 3 months for 2 years ] [ Designated as safety issue: No ]
- Progression Free Survival [ Time Frame: Up to every 3 months for 2 years ] [ Designated as safety issue: No ]
- Disease Free Survival [ Time Frame: Up to every 3 months for 2 years ] [ Designated as safety issue: No ]
- Number of participants with adverse events (Toxicity) [ Time Frame: Days 1, 8, and 15 of each course and 4-6 weeks after final treatment ] [ Designated as safety issue: Yes ]Toxicities and adverse experiences will be assessed at each visit using the NCI Common Toxicity Criteria for Adverse Events v4.0 Interim analyses on toxicity will be implemented based on the toxicity endpoints of the first 6 patients, and will be conducted sequentially 4 weeks after the treatment of each patient, or when serious toxicity has been observed for the patient, whichever comes earlier. we assume a non-informative prior distribution (Beta (0.001, 0.001)) for toxicity rate, and compute the posterior distribution of toxicity rate sequentially.
|Study Start Date:||October 2011|
|Study Completion Date:||July 2013|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (monoclonal antibody and enzyme inhibitor therapy)
Patients receive ofatumumab IV over 2.5 hours on days 1 and 8 of course 1, and day 1 of all subsequent courses. Patients also receive bortezomib IV over 3-5 seconds on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Other Names:Drug: bortezomib
Other Names:Other: laboratory biomarker analysis
Correlative studiesOther: enzyme-linked immunosorbent assay
Other Name: ELISAProcedure: biopsy
Optional correlative studies
Other Name: biopsiesProcedure: quality-of-life assessment
Other Name: quality of life assessmentGenetic: polymorphism analysis
Correlative studiesOther: flow cytometry
I. To determine the efficacy, as measured by overall response (complete response [CR] + partial response [PR]) of ofatumumab in combination with bortezomib in subjects with relapsed cluster of differentiation (CD)20+ DLBCL, FL or MCL.
I. To explore duration of efficacy of ofatumumab in combination with bortezomib in the same population as measured by progression free survival (PFS), overall survival (OS) and disease free survival (DFS).
II. To assess response as compared to prior treatment. III. To assess the safety and tolerability of ofatumumab in combination with bortezomib in the same patient population.
I. Correlation of trough ofatumumab blood levels to response. II. Correlation fragment crystallizable receptor (FcR) gamma 3 allotype and response.
Patients receive ofatumumab intravenously (IV) over 2.5 hours on days 1 and 8 of course 1, and day 1 of all subsequent courses. Patients also receive bortezomib IV over 3-5 seconds on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment patients are followed up every 3 months for 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01397591
|United States, Oregon|
|OHSU Knight Cancer Institute|
|Portland, Oregon, United States, 97239|
|Principal Investigator:||Craig Okada||OHSU Knight Cancer Institute|