Pharmacokinetics and Pharmacodynamics of BI 695500 vs. Rituximab as First Line-treatment in Patients With Low Tumor Burden Follicular Lymphoma
Condition: Lymphoma, Follicular
MeSH terms: Lymphoma; Lymphoma, Follicular
Intervention: BI 695500; MabThera
Intervention description: BI695500, once a week for 4 weeks (4 administrations in total); MabThera, once a week for 4 weeks (4 administrations in total)
Intervention MeSH terms: Rituximab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 95.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of the study is to assess the pharmacokinetic (PK) similarity of
      Boehringer Ingelheim (BI) 695500 vs. rituximab (MabThera®) in previously untreated patients
      with low tumor burden follicular lymphoma (LTBFL).

      The secondary objective of the study is to evaluate the pharmacodynamics (PD), safety, and
      anti-tumor activity of BI 695500 vs. rituximab (MabThera®), as well as the presence of
      anti-drug antibodies (ADAs).
    

Eligibility criteria:

        Inclusion criteria:

          -  Must give written informed consent and be willing to follow this Clinical Trial
             Protocol.

          -  Male or female patients, at least 18 years of age at Screening.

          -  Histologically-confirmed, stage II - IV Non-Hodgkin's lymphoma (CD20+ FL of Grades 1,
             2, or 3a).

          -  Low tumor burden according to the Groupe d'Etudes des Lymphomes Folliculaires (GELF)
             criteria - no nodal or extranodal involvement of more than 7 cm, no more than 3 nodal
             sites with a diameter >3 cm, no B symptoms (i.e., fever >38°C, weight loss -
             unexplained loss of >10 % body weight over the past 6 months, and sweats - the
             presence of drenching night sweats), no significant splenomegaly, no significant
             serious effusion, no complications such as organ compression, and less than 5x10^9/L
             circulating tumor cells.

          -  Availability of archived tumor sample prior to screening.

          -  Patients not previously treated for their FL.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

          -  Have at least 1 measurable lesion as per the International Working Group (IWG)
             criteria 2007 at Screening (lesion clearly measurable in at least 2 perpendicular
             dimensions; see Appendix 10.1 for further details).

          -  Adequate hematological function (unless abnormalities are related to lymphoma
             infiltration of the bone marrow) within 28 days prior to randomization, including:

          -  - hemoglobin =9.0 g/dL (=5.6 mmol/L).

          -  - absolute neutrophil count =1.5 × 10^9/L.

          -  - platelet count =100 × 10^9/L.

          -  Adequate renal and liver function:

          -  - serum creatinine <2.0 mg/dL (<176.8 micromol/L).

          -  - total bilirubin <2.0 mg/dL (<34 mcmol/L) except for patient with Gilbert's Syndrome
             or Hemolysis. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3 x
             upper limit of normal (ULN) (<5 x ULN is acceptable if abnormalities are thought to be
             related to hepatic infiltration by FL).

          -  For participants of reproductive potential (males and females), use of a medically
             acceptable method of contraception during the trial, i.e., a combination of 2 forms of
             effective contraception (defined as hormonal contraception, intrauterine device,
             condom with spermicide, etc.). Females of childbearing potential (includes tubal
             ligation) and males with female partners of childbearing potential must also agree to
             use an acceptable method of contraception (see above) for 12 months following
             completion or discontinuation from the trial medication.

        Exclusion criteria:

          -  Transformation to high-grade lymphoma (secondary to low-grade lymphoma).

          -  Presence or history of central nervous system lymphoma.

          -  Patients receiving current treatment with corticosteroids must not be receiving a dose
             exceeding 20 mg/day prednisone or equivalent.

          -  Patients with prior or concomitant malignancies within 5 years prior to screening
             except non-melanoma skin cancer, adequately treated carcinoma in situ of the cervix,
             adequately treated breast cancer in situ, localized prostate cancer stage T1c -
             provided that the patient underwent curative treatment, and remains relapse free.

          -  Major surgery (excluding lymph node biopsy) within 28 days prior to randomization.

          -  Active, chronic or persistent infection that might worsen with immunosuppressive
             treatment (e.g., Human Immunodeficiency Virus [HIV], Hepatitis C Virus [HCV], Herpes
             Zoster); positive for HIV or tuberculosis at Screening.

          -  Patients with serological evidence of Hepatitis B virus (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.

          -  Serious underlying medical conditions, which, per the investigator's discretion, could
             impair the ability of the patient to participate in the trial (including but not
             limited to ongoing active infection, severe immunosuppression, uncontrolled diabetes
             mellitus, gastric ulcers, active autoimmune disease); 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.

          -  Known hypersensitivity or allergy to murine products.

          -  History of a severe allergic reaction or anaphylactic reaction to a biological agent
             or history of hypersensitivity to any component of the trial drug.

          -  Receipt of a live/attenuated vaccine within 12 weeks prior to the Screening Visit.

          -  Prior treatment with BI 695500 and/or rituximab.

          -  Patients who received any prior therapy using monoclonal antibodies will be excluded;
             this does not apply to other biological drugs such as growth factors or
             anticoagulants.

          -  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.

          -  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.

          -  Pregnancy or breast feeding. For women of childbearing potential, a positive serum
             pregnancy test at the Screening Visit.

          -  Patients who have significant cardiac disease, including but not limited to congestive
             heart failure of Class III or IV of the New York Heart Association (NYHA)
             classification; uncontrolled angina or arrhythmia; any uncontrolled or severe
             cardiovascular or cerebrovascular disease; or uncontrolled hypertension.