BI 695500 vs Rituxan First Line Treatment in Patients With Low Tumor Burden Follicular Lymphoma
Condition: Lymphoma, Non-Hodgkin
MeSH terms: Lymphoma; Lymphoma, Follicular; Lymphoma, Non-Hodgkin
Intervention: Rituximab; BI 695500
Intervention description: BI 695500 375 mg/M2; BI 695500 375 mg/M2
Intervention MeSH terms: Rituximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No

Summary:

      This is a Phase III, multicenter, randomized, double-blind, parallel-arm, active comparator
      trial to evaluate BI 695500 versus rituximab as a first-line immunotherapy treatment in
      patients with LTBFL. Patients will be randomly assigned in a 1:1 ratio to receive 375 mg/m2
      of BI 695500 or rituximab via intravenous (IV) infusion once a week for 4 weeks (total of 4
      dosages administered on Days 1, 8, 15, and 22). Disease assessments will be performed at the
      End of Study (EOS) Visit at Week 30.
    

Eligibility criteria:

        Inclusion criteria:

          1. Written informed consent that is consistent with ICH GCP guidelines and local
             legislations.

          2. Male or female patients, at least 18 years of age at Screening.

          3. Histologically-confirmed, stage II - IV NHL (CD20+ FL of Grades 1, 2, or 3a).

          4. Low tumor burden according to the GELF criteria

          5. Diagnostic biopsies will be centrally reviewed by expert pathologists to confirm
             correct histology in accordance with WHO guidelines. If the interval since diagnosis
             is > 12 months, a new biopsy will be required to confirm the histology remained
             unchanged.

          6. Patients not previously treated for their FL, including any previous treatment for FL
             under clinical trials.

          7. ECOG performance status of 0 to 1.

          8. Have at least one measurable lesion as per the International Working Group (IWG)
             criteria 2007 at Screening (lesion clearly measurable in at least two perpendicular
             dimensions

          9. Adequate hematological function (unless abnormalities are related to lymphoma
             infiltration of the bone marrow) within 28 days prior to randomization

         10. Adequate renal and liver function:

         11. For participants of reproductive potential (males and females), use of a medically
             acceptable method of contraception during the trial

        Exclusion criteria:

          1. Transformation to high-grade lymphoma (secondary to low-grade lymphoma) prior to study
             entry.

          2. Circulating tumor cells = 5 × 109/L.

          3. Presence or history of central nervous system lymphoma.

          4. Patients receiving current treatment with corticosteroids must not be receiving a dose
             exceeding 20 mg/day prednisone or equivalent.

          5. Patients with prior or concomitant malignancies within 5 years prior to Screening

          6. Major surgery within 28 days prior to randomization.

          7. Active, chronic or persistent infection that might worsen with immunosuppressive
             treatment; positive for HIV or tuberculosis (TB) at Screening. Patients who are
             confirmed positive and those who have active infections are excluded from the trial
             participation.

          8. Patients with serological evidence of HBV infection. Patients seropositive because of
             HBV vaccine are eligible. HBV positive patients may participate following consultation
             with a hepatitis expert regarding monitoring and use of HBV antiviral therapy, and
             provided they agree to receive treatment as indicated.

          9. Serious underlying medical conditions, that, per the Investigator¿s discretion, could
             impair the ability of the patient to participate in the trial.

         10. Known hypersensitivity or allergy to murine products.

         11. History of a severe allergic reaction or anaphylactic reaction to a biological agent
             or history of hypersensitivity to any component of the trial medication.

         12. Receipt of a live/attenuated vaccine within 12 weeks prior to the Screening Visit.

         13. Prior treatment with BI 695500 and/or rituximab.

         14. Patients who received any prior therapy using mAbs will be excluded; this does not
             apply to other biological drugs such as growth factors or anticoagulants.

         15. Treatment within a clinical trial within 4 weeks prior to initiation of trial
             treatment. Patients who have received treatment with a drug that has not received
             regulatory approval for any indication within 4 weeks or a minimum of 5 half-lives,
             whichever is longer, of the initial dose of trial medication.

         16. Any other co-existing medical or psychological condition(s) that will preclude
             participation in the trial or compromise ability to give informed consent and/or
             comply with study procedures.

         17. Pregnancy or breast feeding. For women of childbearing potential, a positive serum
             pregnancy test at the Screening Visit.

         18. Patients who have significant cardiac disease, including but not limited to congestive
             heart failure of Class III or IV of the NYHA classification; uncontrolled angina or
             arrhythmia; any uncontrolled or severe cardiovascular or cerebrovascular disease; or
             uncontrolled hypertension.