Phase II Randomized Trial Comparing GA101 and Rituximab in Untreated Low Tumor Burden Indolent Non-Hodgkin's Lymphoma
Condition: Indolent Non-Hodgkin's Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: Arm A: Rituximab; Arm B: GA101
Intervention description: Rituximab 375 mg/m² IV x 4 weekly doses.; GA101 1,000 mg (flat dose) IV x 4 weekly doses.
Intervention MeSH terms: Rituximab; Obinutuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Untreated Non-Hodgkin's Lymphoma; Low Tumor Burden Non-Hodgkin's Lymphoma; NHL; Indolent; Rituximab; Rituxan; GA101; Obinutuzumab

Summary:

      Patients with previously untreated low tumor burden indolent Non-Hodgkin's Lymphoma (NHL)
      will receive either rituximab or GA101 weekly for 4 weeks followed by re-staging to determine
      response.

      Rituximab, an anti-CD20 chimeric antibody, was approved by the United States Food and Drug
      Administration in 1998 for the treatment of patients with relapsed low-grade B-cell
      lymphomas. Clinically, four weekly doses of rituximab have proven to be well tolerated and
      effective in previously untreated as well as relapsed patients with low-grade lymphoma.

      GA101 is an anti-CD20 humanized and glyco-engineered monoclonal antibody. GA101 has been
      shown to have increased antibody-dependent cellular cytotoxicity (ADCC) and direct cell-death
      induction compared to Rituximab. It is possible that GA101 may have greater efficacy than
      rituximab.

      PrE0401 Sub-Study Evaluation of Corrected QT (QTc) Interval and Pharmacokinetic Parameters in
      Patients Participating in GA101 (Obinutuzumab)

      Approximately twenty-five patients randomized to GA101 may participate in the sub-study.
      Electrocardiograms and blood samples will be obtained.
    

Eligibility criteria:

        Inclusion Criteria:

        Registration: Patients having both diffuse and follicular architectural elements will be
        considered eligible if the histology is predominantly follicular (≥ 50% of the
        cross-sectional area), and there is no evidence of transformation to a large cell
        histology.

          -  Biopsy-proven diagnosis of Grade 1 or 2 follicular non-Hodgkin's lymphoma with no
             evidence of transformation to large cell histology.

          -  Meet criteria for Low Tumor Burden:

               -  No nodal or extra nodal mass ≥ 7 centimeter (cm)

               -  <3 nodal masses >3 cm in diameter

               -  No systemic symptoms or B symptoms

               -  No splenomegaly >16 cm by CT scan

               -  No risk of compression of a vital organ.

               -  No leukemic phase with >5000/mm³ circulating lymphocytes.

          -  No cytopenias defined as:

               -  Platelets <100,000/mm³

               -  Hemoglobin (Hgb) <10 g/dL

               -  Absolute Neutrophil Count (ANC) <1500/mm³

          -  Must have Stage III or Stage IV disease.

          -  Baseline measurements/evaluations obtained within 6 weeks of registration. Patient
             must have at least one objective measurable disease parameter.

          -  Age ≥ 18 years.

          -  Eastern Oncology Cooperative Group Performance Status 0-1.

          -  Must not have received investigational agents within 30 days of registration.

          -  Signed Institutional Review Board (IRB)-approved informed consent.

          -  Willing to provide blood samples for research purposes.

          -  Women must not be pregnant or breastfeeding.

          -  Women of childbearing potential and sexually active males must use an accepted and
             effective method of contraception.

          -  No prior chemotherapy, radiotherapy or immunotherapy for lymphoma.

          -  No prior treatment with cytotoxic drugs or rituximab for a previous cancer or another
             condition (e.g. rheumatoid arthritis) or prior use of an anti-CD20 antibody.

          -  No prior use of any monoclonal antibody within 3 months of randomization.

          -  No history of severe allergic/anaphylactic reactions to humanized/murine monoclonal
             antibodies or known sensitivity/allergy to murine products.

          -  No history of prior malignancy except for adequately treated basal cell or squamous
             cell skin cancer, in situ cervical cancer, or other cancer for which the patient has
             been disease-free for at least 2 years and did not require treatment with cytotoxic
             drugs or rituximab.

          -  No major surgery within 4 weeks prior to randomization, other than for diagnosis.

          -  Must be Human Immunodeficiency Virus (HIV) negative.

          -  Have adequate organ function without growth factor and/or transfusion support within ≤
             2 weeks prior to registration:

               -  ANC ≥ 1500/mm³

               -  Hgb ≥ 10 g/dL

               -  Platelets ≥ 100,000/mm³

               -  Serum Creatinine ≤ 2x Upper Limit Normal (ULN)

               -  Total Bilirubin ≤ 2x ULN

               -  AST (aspartate aminotransferase)/ALT (alanine aminotransferase) ≤ 5x ULN

               -  PTT (Partial Thromboplastin Time) or aPTT (activated Partial Thromboplastin Time)
                  >1.5x the ULN in the absence of a lupus anticoagulant

               -  INR (International Normalized Ratio) >1.5x the ULN in the absence of therapeutic
                  anticoagulation

          -  No active, uncontrolled infections (afebrile for ≥ 48 hours off antibiotics).

          -  Must not receive immunization with attenuated live vaccines within 28 days prior to
             registration or during the study period.

          -  Must be tested for hepatitis B surface antigen (HBsAg) and total hepatitis B core
             antibody (anti-HBc) within 2 weeks of registration. Patients who are chronic carriers
             of HBsAg and anti-HBc are excluded.

          -  Must be tested for hepatitis C antibody within 2 week of registration. If this test is
             positive, patients are excluded unless a hepatitis C virus ribonucleic acid (HCV RNA)
             is negative.

          -  No evidence of significant, uncontrolled concomitant diseases that could affect
             compliance with the protocol or interpretation of results, including significant
             cardiovascular disease (i.e., severe arrhythmia, myocardial infarction within the
             previous 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease.