Pilot Study of Bortezomib, Bendamustine and Rituximab on Non-Hodgkin's Lymphoma
Condition: Non-Hodgkin's Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: bortezomib; bendamustine; rituximab
Intervention description: 1.3 mg/m^2 on days 1, 4, 8, 11; 90 mg/m^2 days 1 and 4; 375 mg/m^2 day 1
Intervention MeSH terms: Rituximab; Bortezomib; Bendamustine Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Bortezomib; Bendamustine; Rituximab; Relapsed; Refractory; Mantle Cell; Indolent

Summary:

      The purpose of this study is to evaluate how non-Hodgkin's lymphoma that has not responded
      to, or that has returned after standard treatment, responds to bortezomib, rituximab and
      bendamustine, and also to see what effects this drug combination have on this cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Voluntary written informed consent before performance of any study-specific procedure
             not part of routine medical care, with the understanding that consent may be withdrawn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
             acceptable method of birth control for duration of study.

          -  Male subject agrees to use acceptable method for contraception for duration of study.

          -  Histologically-confirmed indolent or mantle cell lymphoma, utilizing the World Health
             Organization (WHO) classification. The biopsy must fulfill one of the following
             criteria:

               -  Follicular lymphoma, grades 1-3

               -  Marginal zone lymphoma

               -  Small lymphocytic lymphoma (circulating lymphocyte count must be < 5,000)

               -  Lymphoplasmacytic lymphoma

               -  Mantle cell lymphoma [confirmed by cyclin D1+ or FISH for t(11;14)]

          -  Age ≥ 18 years

          -  Must have received at least one prior chemotherapy regimen for lymphoma. Patients
             treated only with antibody therapy or only with radiation therapy are not eligible.

          -  Zubrod performance status ≤ 3

          -  Patients must have measurable disease or an indication to receive additional therapy

        Exclusion Criteria:

          -  Patient has platelet count of ≤75,000/mm^3 within 14 days before enrollment.

          -  Patient has absolute neutrophil count of < 1,000/mm^3 within 14 days before
             enrollment.

          -  Patient has calculated or measured creatinine clearance of <30 mL/minute within 14
             days before enrollment.

          -  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 Class III or IV heart failure, 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 subject is not pregnant
             must be established by negative serum ß-human chorionic gonadotropin (ß-hCG) pregnancy
             test result obtained during screening. Pregnancy testing is not required for
             post-menopausal or surgically sterilized women.

          -  Patient has received chemotherapy or antibody therapy within 28 days before enrollment

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study.

          -  Patient has received other investigational drugs with 14 days before enrollment

          -  Diagnosed or treated for another malignancy within 3 years of enrollment, with the
             exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
             the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.

          -  Prior exposure to bendamustine

          -  Prior exposure to bortezomib if Time to Progression (TTP) after bortezomib containing
             regimen was < 6 months. If TTP after bortezomib containing regimen was > 6 months,
             then patient is allowed to enroll on the study.

          -  Patient has concomitant active malignancy requiring therapy

          -  Patient is known to be HIV positive (test result not required for enrollment).

          -  History of solid organ transplantation, or post transplant lymphoproliferative
             disorder

          -  Patient has history of allogeneic stem cell transplantation.

          -  Patient has history of autologous stem cell transplantation or radioimmunotherapy
             within the previous 4 months.

          -  Patient has received any other investigational drugs within 14 days prior to
             enrollment

          -  History of, or clinically apparent CNS lymphoma

          -  Any clinically significant abnormality in screening blood chemistry, hematology, or
             urinalysis results that, in the judgment of the investigator, would impede adequate
             evaluation of adverse events and/or response to treatment, or that requires aggressive
             intervention