Ofatumumab and Bortezomib in Subjects With Relapsed CD20+Diffuse Large B Cell, Follicular, or Mantle Cell Lymphoma

NCT01397591 | Terminated Phase 2 Results DMC

• 3 other identifiers: IRB00007042NCI-2011-01032OFT113735
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Response Rate of Ofatumumab in Combination With Bortezomib in Patients With Relapsed CD20+ (Cluster of DIfferentiation Antigen 20) Diffuse Large B Cell Lymphoma, Follicular Lymphoma, or Mantle Cell Lymphoma

  Based on International Working Group (IWG) criteria, recorded in four categories: Complete Response (CR), disappearance of all evidence of disease; Partial Response (PR), regression of measurable disease and no new sites of disease; Progressive Disease (PD), Any new lesion or increase by \>= 50% of previously involved sites from nadir. Stable Disease (SD), failure to attain CR/PR or PD. A response is defined to be either CR/PR. A failure in response includes SD/PD.

  Every 2 cycles during treatment and then every 3 months for 2 years

Secondary Outcomes (4)

• Overall Survival

  Up to every 3 months for 2 years

• Progression Free Survival

  Up to every 3 months for 2 years

• Disease Free Survival

  Up to every 3 months for 2 years

• Number of Participants With Adverse Events (Toxicity)

  Days 1, 8, and 15 of each course and 4-6 weeks after final treatment

Study Arms (1)

Ofatumumab with Bortezomib

EXPERIMENTAL

Ofatumumab was given intravenously on cycle 1 day 1 at a dose of 300mg, followed by a cycle 1 day 8 dose of 1000mg. During cycles 2 through cycle 6, Ofatumumab was given at a dose of 1000mg on day 1 of each cycle, with no dosing on any other day of the cycle. Bortezomib was given intravenously at a dose of 1.6mg/m2 on days 1, 8, and 15 of each cycle, following the Ofatumumab infusion, if given.

Biological: Ofatumumab; Drug: Bortezomib

Interventions

Ofatumumab BIOLOGICAL

Given intravenously

Also known as: Arzerra, HuMax-CD20

Ofatumumab with Bortezomib

Bortezomib DRUG

Given intravenously

Also known as: LDP 341, MLN341, VELCADE

Ofatumumab with Bortezomib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have biopsy sample obtained within 6 months of study entry that:
• Is histologically confirmed DLBCL, MCL or FL, by an Oregon Health and Science University (OHSU) hematopathologist
• Retains expression of CD20+
• Patients must be refractory to or have recurrent disease after prior rituximab containing treatment; relapse or progression is defined according the International Working Group (IWG) response criteria
• FL patients must have disease-related symptoms, cytopenias, threatened end-organ function, bulky or progressive disease, or it is the patient's preference to be treated
• DLBCL and MCL patients must be either transplant ineligible or have refused high dose therapy
• Patients must have radiographically measurable disease, as defined by the IWG criteria; the same method of assessment used to measure each lesion at baseline must be used for all subsequent tumor measurements throughout the study
• There is no limit to the number of prior treatments
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Absolute neutrophil count \>= 1.0 K/mm\^3
• Platelets \>= 50 K /mm\^3
• Total bilirubin =\< 1.5 x normal institutional limits, unless secondary to Gilbert's disease
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase (SGOT))/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase (SGPT)) =\< 2.5 x institutional upper limit of normal (ULN)
• Alkaline Phosphatase \< 2.5 times ULN (unless due to disease involvement of the liver or bone marrow)
• Patients must be able to comply with study procedures and follow-up examinations

You may not qualify if:

• Subjects who have current active hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
• Patients who have had chemotherapy, antibody or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C); corticosteroids for symptom control are allowed up to 7 days of starting protocol treatment
• Patients may not have received any other investigational agents within 4 weeks, or may not be currently participating in any other interventional clinical study
• Prior treatment with ofatumumab or bortezomib
• Prior treatment with anti-CD20 monoclonal antibody or alemtuzumab within 3 months prior to start of therapy
• Diagnosis of another malignancy, unless the patient has been disease-free or at least 5 years following the completion of curative intent therapy with the following exceptions: patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed; patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ofatumumab or bortezomib
• Peripheral neuropathy or neuropathic pain of Grade 2 or greater
• Chronic or current infectious disease requiring systemic antibiotics, antifungal, or anti-viral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis and tuberculosis
• History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae
• Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (New York Heart Association (NYHA) III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities
• Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient
• Pregnant or breast feeding women
• Known human immunodeficiency virus (HIV) infection
• Positive serology for Hepatitis B (HB) defined as a positive test for HB surface antigen (HBsAg); in addition, if negative for HBsAG but HB core antibody (HBcAb) positive (regardless of HBsAb status), a HB deoxyribonucleic acid (DNA) test will be performed; if positive the subject will be excluded

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• National Cancer Institute (NCI): collaborator
• Millennium Pharmaceuticals, Inc.: collaborator
• GlaxoSmithKline: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell

Interventions

ofatumumab; Bortezomib

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Jeff Donovan
• Organization: OHSU Knight Investigational Cancer Services

mastersj@ohsu.edu

503-494-7702

Study Officials

• Craig Okada

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2011
• First Posted: July 19, 2011
• Study Start: October 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: July 1, 2013
• Last Updated: July 30, 2014
• Results First Posted: July 30, 2014

Record last verified: 2014-07

Locations

US (1)