To Determine the Dose of BI 836826-GemOx and the Efficacy of BI 836826-GemOx Versus R-GemOx in Patients With Relapsed/Refractory DLBCL
Condition: Lymphoma, Large B-Cell, Diffuse
MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse
Intervention: BI 836826; GemOx; Rituximab; GemOx
Intervention MeSH terms: Rituximab; BI 836826
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Part 1 (Phase Ib)

      Primary objective:

      To establish the maximum tolerated dose (MTD) of BI 836826 in combination with GemOx.

      Secondary objectives:

      To evaluate pharmacokinetics of BI 836826 when given in combination with GemOx and to
      investigate preliminary efficacy in terms of the overall response rate based on
      investigator's assessment.

      Part 2 (Phase II randomized)

      Primary objective:

      To investigate the efficacy by means of the overall response rate (PR+ CR) based on central
      review assessment in patients with relapsed DLBCL treated with BI 836826-GemOx compared to
      R-GemOx.

      Secondary objective:

      To investigate the efficacy by means of the complete remission rate based on central review
      assessment in patients with relapsed DLBCL treated with BI 836826-GemOx compared to Rituximab
      + gemcitabine + oxaliplatin (RGemOx).
    

Eligibility criteria:

        Inclusion criteria:

          -  Age 18 years or older

          -  Patients with histologically confirmed, relapsed/refractory, diffuse large B-cell
             lymphoma (including transformed follicular lymphoma) who have received an
             anti-CD20-supplemented, anthracycline-containing chemotherapy and are not eligible for
             high dose therapy followed by an autologous stem cell transplant, or have
             relapsed/progressed after autologous/allogenic stem cell transplant. Allogenic stem
             cell transplant performed at least 6 months prior to study entry is allowed if
             patients do not require immunosuppressive treatment and have no evidence of active
             graft-versus-host disease.

          -  Patient has not received anti-lymphoma treatment prior to the first dose of trial
             medication: within past 14 days or within time that is shorter or equal to 5
             half-lives of the drug if the last anti-lymphoma treatment contained an
             investigational agent

          -  Screening computer tomography (CT) scan with involvement of at least 1 bi-dimensional
             lesion/node >1.5 cm

          -  Screening [18F] fluorodeoxyglucose (FDG)- positron emission tomography (PET) scans
             must demonstrate positive lesion compatible with computer tomography (CT) defined
             anatomical tumor sites

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2

          -  Written signed informed consent consistent with International Conference on
             Harmonization (ICH) Good Clinical Practice (GCP) and local legislation

          -  Patients must have an acceptable organ function

          -  Women of childbearing potential must be ready and able to use highly effective methods
             of birth control per ICH M3(R2) that result in a low failure rate of less than 1% per
             year when used consistently and correctly. Non-vasectomized male patients having a
             female sexual partner of childbearing potential must ensure their partner is using a
             highly effective method of birth control as described above, during the trial and for
             at least 12 months after the end of the trial.

        Exclusion criteria:

          -  Eligible for curative salvage high dose therapy followed by stem cell transplant

          -  Primary central nervous system lymphoma or known Central nervous system (CNS)
             involvement

          -  Prior history of malignancy other than DLBCL except basal cell or squamous cell
             carcinoma of the skin, or carcinoma in situ of the uterine cervix or breast which has
             been treated with curative therapy. Other prior malignancies are allowed only if
             patient has been free of disease and without treatment other than hormones for at
             least past three years.

          -  Refractory to gemcitabine and/or oxaliplatin

          -  Contraindications for gemcitabine, oxaliplatin and/or rituximab as judged by the
             investigator. Hypersensitivity to oxaliplatin

          -  Unresolved toxicity of CTCAE grade > 1from prior anti-lymphoma therapy (except
             alopecia)

          -  Significant concurrent medical disease or condition which according to the
             investigators judgment would either compromise patient safety or interfere with the
             evaluation of the safety of the test drug. e.g. symptomatic congestive heart failure,
             unstable angina pectoris, cardiac arrhythmia requiring therapy with the exception of
             extra systoles of minor conduction abnormalities

          -  An infection requiring treatment at the start of the trial medication.

          -  Active hepatitis B or hepatitis C, or laboratory evidence for a chronic infection or
             HIV infection (test results done in routine diagnostics are acceptable if done within
             14 days before the first study treatment dose)

          -  Women who are pregnant, nursing, or who plan to become pregnant while in the
             trial.This includes the female sexual partners of a male participant

          -  Known alcohol or drug abuse which could potentially interfere with trial participation
             according to investigators judgment

          -  Prior treatment with CD37 antibody