Study of VELCADE and Rituximab in Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma
Condition: Non-Hodgkin's Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell
Intervention: Bortezomib + Rituximab; Rituximab
Intervention description: VELCADE for Injection will be administered weekly on Days 1,8,15, and 22 of a 35-day cycle in combination with 4 doses of rituximab once a week on Days 1,8,15, and 22 of Cycle 1 and in combination with a single dose of rituximab on Day 1 of Cycles 2 to 5.; rituximab once a week on Days 1,8,15, and 22 of Cycle 1, and as a single dose on Day 1 of Cycles 2 to 5 (for a total of 8 doses).
Intervention MeSH terms: Rituximab; Bortezomib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 676.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: B-cell Non-Hodgkin's Lymphoma

Summary:

      The purpose of this study is to determine if the combination of VELCADE and rituximab
      improves progression free survival relative to rituximab alone in patients with relapsed or
      refractory B-cell non-Hodgkin's lymphoma (B-NHL) who never received rituximab or who have
      previously responded to rituximab. This is an international study being conducted in the
      United States and in many countries around the world. A complete list of study locations is
      listed below.
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects must satisfy the following criteria to be enrolled in the study:

          -  Man or woman and age 18 years or older

          -  Diagnosis of follicular B-NHL of the following subtypes (World Health Organization
             [WHO] classification 1997): follicular lymphoma (FL) (Grades 1 and 2).

          -  Documented relapse or progression following prior antineoplastic treatment. New
             lesions or objective evidence of progression of existing lesions must document relapse
             or progression following the previous therapy.

        If any prior regimen included rituximab, the subject must have responded (complete response
        [CR], unconfirmed complete response [CRu], partial response [PR]), and the time to
        progression (TTP) from the first dose of rituximab must have been 6 months or more.

          -  At least 1 measurable tumor mass (greater than 1.5 cm in the longest dimension and
             greater than 1.0 cm in the short axis) that has not been previously irradiated, or has
             grown since previous irradiation

          -  In the opinion of the investigator the decision to initiate treatment is justified to
             manage the subject's lymphoma

          -  No active central nervous system lymphoma

          -  Eastern Cooperative Oncology Group [ECOG] status ≤ 2

          -  Female subjects must be postmenopausal (for at least 6 months), surgically sterile,
             abstinent, or, if sexually active, be practicing an effective method of birth control
             (e.g., prescription oral contraceptives, contraceptive injections, intrauterine
             device, double-barrier method, contraceptive patch, male partner sterilization) before
             entry and throughout the study; and have a negative serum beta-human chorionic
             gonadotropin (β-hCG) pregnancy test at screening.

          -  Subjects (or their legally acceptable representatives) must have signed an informed
             consent document indicating that they understand the purpose of and procedures
             required for the study and are willing to participate in the study.

          -  In countries where health authorities have approved the pharmacogenomic testing,
             subjects or their legally acceptable representatives must have signed a separate
             informed consent that they agree to participate in the genetic part and protein
             testing part of the study; participation in the genetic and protein testing component
             is mandatory for pharmacogenomics testing, but optional for serum protein testing and
             future testing.

        Exclusion Criteria:

        Potential subjects who meet any of the following criteria will be excluded from
        participating in the study:

          -  Diagnosed or treated for a malignancy other than NHL within 1 year of randomization,
             or who were previously diagnosed with a malignancy other than NHL and have any
             radiographic or biochemical marker evidence of malignancy. Subjects with completely
             resected basal cell carcinoma, squamous cell carcinoma of the skin, or in situ
             malignancy are not excluded.

          -  Clinical evidence of a transformation from indolent NHL to a more aggressive form of
             NHL.

          -  History of disallowed therapies:

               -  Prior treatment with VELCADE

               -  Antineoplastic (including unconjugated therapeutic antibodies), experimental, or
                  radiation therapy within 3 weeks before randomization

               -  Nitrosoureas within 6 weeks before randomization

               -  Radioimmunoconjugates or toxin immunoconjugates within 10 weeks before
                  randomization

               -  Stem cell transplant within 6 months before randomization

               -  Major surgery within 2 weeks before randomization

          -  Residual toxic effects of previous therapy or surgery of Grade 3 or worse

          -  Peripheral neuropathy or neuropathic pain of Grade 2 or worse

          -  Have received an experimental drug or used an experimental medical device within 21
             days before the planned start of treatment.

          -  History of allergic reaction attributable to compounds containing boron or mannitol

          -  Known anaphylaxis or immunoglobulin E (IgE)-mediated hypersensitivity to murine
             proteins or to any component of rituximab including polysorbate 80 and sodium citrate
             dihydrate

          -  Concurrent treatment with another investigational agent

          -  Female subject who is pregnant or breast-feeding