To Determine the Dose of BI 836826-GemOx and the Efficacy of BI 836826-GemOx Versus R-GemOx in Patients With Relapsed/Refractory DLBCL

An Open Label Multicenter Phase Ib/II Trial to Determine the Dose of BI 836826 in Combination With Gemcitabine and Oxaliplatin (GemOx) and the Efficacy of BI 836826-GemOx Versus Rituximab (R)- GemOx (R-GemOx) in Patients With Relapsed/ Refractory Diffuse Large B-cell Lymphoma (DLBCL) Who Are Not Eligible for, or Have Relapsed/Progressed After Autologous/Allogeneic Stem Cell Transplant

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).

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