High Dose Rituximab for Initial Treatment of Indolent B-Cell Lymphomas
Condition: B-cell Lymphoma; Indolent B-cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell
Intervention: rituximab
Intervention description: Increased dose (750 mg/m2) intravenously for 4 weekly doses followed by maintenance dosing once every three months for up to 2 years. Maintenance dose is standard (375 mg/m2).
Intervention MeSH terms: Rituximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: rituximab

Summary:

      The purpose of this clinical trial is to see if increased doses of rituximab are safe and
      effective for the initial treatment of indolent B-cell lymphomas. Rituximab (Rituxan) is a
      type of drug called an "antibody" that specifically targets B-cell lymphoma cells, and is
      approved by the FDA for the treatment of indolent B-cell non-hodgkin lymphomas and certain
      other types of non-hodgkin lymphomas. Standard doses currently used may not be achieving
      maximal efficacy. Higher doses have been shown to be safe in other clinical trials, and may
      offer superior efficacy to the current standard dose. This trial also employs intermittent
      maintenance doses of rituximab at the standard dose, which has been shown to prolong
      remissions and survival in patients with relapsed indolent B-cell lymphomas. This trial is
      designed to show that higher dose rituximab plus maintenance rituximab can achieve similarly
      good results to chemotherapy approaches, but without chemotherapy-related toxicity.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Indolent B-Cell NHL of the following histologies:

               1. Follicular lymphoma (grades 1-3A);

               2. marginal zone lymphoma (extranodal, nodal or splenic):

                    -  Extranodal marginal zone lymphomas (MALT lymphomas) may not be candidates
                       for cure with antibiotics or local radiotherapy. Patients who have failed
                       antibiotics or local therapy are eligible for the protocol as long as they
                       have measurable disease and are naive to chemotherapy and monoclonal
                       antibody;

                    -  splenic marginal zone lymphoma patients may have received prior splenectomy
                       as long as they have measureable disease and are naive to chemotherapy and
                       monoclonal antibody therapy;

               3. Small lymphocytic lymphoma (must have less than 5000 circulating clonal
                  B-lymphocytes);

               4. Indolent CD20+ B-cell lymphoma not otherwise specified with CD20+ expression

          -  Measurable disease, defined as at least one lesion that can be accurately measured in
             at least one dimension (longest diameter to be recorded) as 20mm or greater with
             conventional techniques or as 10mm or greater with spiral CT scan

          -  No previous chemotherapy, antibody therapy or radioimmunotherapy for NHL. Patients
             previously treated with external bean radiation alone, surgery, or with antibiotics
             are eligible

          -  18 years of age or older

          -  Life expectancy of greater than 3 months

          -  ECOG performance status of 2 or less

          -  Adequate bone marrow function

          -  Use of adequate contraception

        Exclusion Criteria:

          -  Prior chemotherapy, monoclonal antibody therapy or radioimmunotherapy for lymphoma

          -  Receiving any other investigational agent

          -  Known brain metastases

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to rituximab

          -  HIV positivity

          -  Active hepatitis B infection

          -  Candidate for curative radiotherapy, unless radiation therapy is considered too toxic
             (as in abdominal disease), or is refused by the patient

          -  NYHA Classification III or IV disease

          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active
             infection that is not optimally treated with antibiotics, unstable angina pectoris, or
             psychiatric illness/social situations that would limit compliance with study
             requirements

          -  Pregnant women

          -  Individuals with a history of a different malignancy except for the following
             circumstances:

               1. disease-free for at least 1 year and are deemed by the investigator to be at low
                  risk for recurrence of that malignancy;

               2. localized prostate cancer, prostate cancer with elevated PSA but no measurable
                  disease on CT scans or bone scan, cervical cancer in situ; and

               3. non-melanoma skin cancers