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

Phase 2
18 Years
Open (Enrolling)
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

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Trial Information

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


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.

Inclusion Criteria:

- 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

- DLBCL and MCL patients must be either transplant ineligible or have refused high dose

- 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

- 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

- Women of childbearing potential (not surgically sterile or < 12 months naturally
post-menopausal) must be willing to use medically accepted method of contraception
for the duration and 6 months following the end of the treatment; acceptable methods
of contraception include abstinence, barrier method with spermicidal or hormonal
contraceptive (oral, transdermal, implanted and injected) in conjunction with a
barrier method

- Men who are not surgically sterile must practice abstinence or use a barrier method
of birth control for the duration and 6 months following the end of treatment

- Patients must have the ability to understand and the willingness to sign a written
informed consent document

Exclusion Criteria:

- 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

- Active hepatitis C infection (HC) defined as a positive test for HCAb, in which case
the investigator should reflexively perform a HC Recombinant Immunoblot assay (RIBA)
on the same sample to confirm the result

- Known lymphoma involvement of the central nervous system (CNS)

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

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.

Outcome Time Frame:

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

Safety Issue:


Principal Investigator

Craig Okada

Investigator Role:

Principal Investigator

Investigator Affiliation:

OHSU Knight Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

October 2011

Completion Date:

Related Keywords:

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



OHSU Knight Cancer Institute Portland, Oregon  97239