Ofatumumab and Bortezomib for Patients With Low-grade B-cell Non-hodgkin Lymphoma That Relapse After Rituximab
Condition: Lymphoma, Non-Hodgkins
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: Ofatumumab and Bortezomib
Intervention description: Ofatumumab 1000 mg IV Cycle 1 on day 1, 8, 15 and 22 Bortezomib 1.6 mg/m2 IV Ofatumumab 1000 mg IV on day 1 maintenance phase Patients will remain until progression
Intervention MeSH terms: Bortezomib; Ofatumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: B-cell small lymphocytic lymphoma; marginal zone lymphoma; follicular lymphoma; mantle cell lymphoma; Waldenström macroglobulinemia.; Low Grade B cell Non-Hodgkins Lymphoma

Summary:

      The purpose of this study is to: Investigate the Overall Response Rate (ORR) of the
      combination of ofatumumab and bortezomib in patients with low-grade B-cell non-Hodgkin
      lymphoma (LG-NHL) that relapse beyond 6 months of a previous rituximab-containing regimen.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients are required to have histologically confirmed lymphoma according to the
             WHO/Revised European-American Lymphoma classification, including B-cell small
             lymphocytic lymphoma (SLL); marginal zone lymphoma (MZL); follicular lymphoma (FL),
             grades 1, 2, or 3; mantle cell lymphoma (MCL); and Waldenström macroglobulinemia.
             Prior history of transformed lymphoma is permitted as long as recent biopsies revealed
             no evidence of aggressive lymphoma and it has been > 3years since prior aggressive
             lymphoma

          -  Patients must measurable disease (defined as 1 cm with spiral computed tomography
             scan)

          -  Relapse of disease beyond 6 months after rituximab-containing regimen

          -  Patients had to have received no more than three prior lines of conventional cytotoxic
             therapy, and were required to have stopped receiving cytotoxic chemotherapy for at
             least 4 weeks before study enrollment

          -  Absolute neutrophil count > 1,500/uL and Platelet > 100,000/uL (if known lymphomatous
             involvement of the bone marrow, then absolute neutrophil count > 750/uL and platelet
             count of > 50,000/uL) within 14 days of enrollment.

          -  Total bilirubin < 1.5 x upper institutional limit of normal (ULN), and AST or ALT <
             2.5 x ULN (< 3 x ULN if the patient had liver involvement); alkaline phosphatase <
             2.5x upper limit of normal; and a creatinine < 2mg/dl within 14 days of enrollment.

          -  ECOG performance status 0 to 2

          -  Minimum life expectancy of 6 months

          -  Age older than 18 years

          -  Voluntary, signed written informed consent before performance of any study-related
             procedure not part of normal medical care, with the understanding that consent may be
             withdrawn by the subject at any time without prejudice to future medical care.

          -  Female subject is either post-menopausal or surgically sterilized or willing to use an
             acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine
             device, diaphragm with spermicide, condom with spermicide, or abstinence) for the
             duration of the study.

          -  Male subject agrees to use an acceptable method for contraception for the duration of
             the study.

        Exclusion Criteria:

          -  Subjects who have current active hepatic or biliary disease asymptomatic gallstones,
             liver metastases or stable chronic liver disease per investigator assessment)

          -  Documented infection with HIV

          -  Positive serology for Hepatitis B defined as a positive test for HBsAg. In addition,
             if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test
             will be performed and if positive the subject will be excluded.

          -  Central nervous system or meningeal involvement by lymphoma

          -  Prior transplantation

          -  Contraindication to any drug contained in the chemotherapy regimens

          -  Any serious active disease or co-morbid condition that would impair protocol
             treatment.

          -  Diagnosed or treated for another malignancy within 3 years of enrollment, with the
             exception of complete resection of basal call carcinoma or squamous cell carcinoma of
             the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.

          -  Prior treatment with any anti-CD20 monoclonal antibody, with the exception of
             rituximab, or any proteasome inhibitor.

          -  Patient has Grade 2 peripheral neuropathy within 14 days before enrollment.

          -  Myocardial infarction within 6 months prior to enrollment or has New York Heart
             Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled
             angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence
             of acute ischemia or active conduction system abnormalities. Prior to study entry, any
             ECG abnormality at screening has to be documented by the investigator as not medically
             relevant.

          -  Patient has hypersensitivity to boron or mannitol.

          -  Female subject is pregnant or breast-feeding. Confirmation that the subject is not
             pregnant must be established by a negative serum pregnancy test result obtained during
             screening. A pregnancy test must be performed within 7 days prior to study drug.
             Pregnancy testing is not required for post-menopausal or surgically sterilized women.

          -  Patient has received other investigational drugs within 4 weeks before enrollment or 5
             half lives of the investigational agent.

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study.