Intravenous BI 836826 in Combination With Ibrutinib in Relapsed/Refractory CLL Patients Who Have Been Pre-treated With at Least One Prior Line of Systemic Therapy, and Who Are Eligible for Treatment With Ibrutinib
Intravenous BI 836826 in Combination With Ibrutinib in Relapsed/Refractory CLL Patients Who Have Been Pre-treated With at Least One Prior Line of Systemic Therapy, and Who Are Eligible for Treatment With Ibrutinib
Intravenous BI 836826 in combination with ibrutinib in relapsed/refractory Chronic
 Lymphocytic Leukemia (CLL) patients who have been pre-treated with at least one prior line of
 systemic therapy, and who are eligible for treatment with ibrutinib. Objectives of the trial
 are to determine the recommended Phase 2 dose of BI 836826, and to document the safety and
 tolerability of BI 836826 when given in combination with ibrutinib
Inclusion criteria:

 -  Diagnosis of Chronic Lymphocytic Leukemia (CLL) established according to International
 Workshop Chronic Lymphocytic Leukemia (IWCLL) criteria.

 -  Relapsed or refractory CLL pre-treated with at least one prior line of systemic
 therapy for CLL.

 -  Indication for treatment consistent with IWCLL criteria, i.e. at least one of the
 following criteria should be met

 -  Evidence of progressive marrow failure as manifested by the development of, or
 worsening of, anemia and/or thrombocytopenia.

 -  Massive or progressive or symptomatic splenomegaly.

 -  Massive nodes or progressive or symptomatic lymphadenopathy.

 -  Progressive lymphocytosis in the absence of infection, with an increase in blood
 Absolute Lymphocyte Count (ALC) >=50% over a 2-month period, or a lymphocyte doubling
 time (LDT) of <6 months (as long as initial ALC was >=30000/µl).

 -  Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids
 or other standard therapy.

 -  Constitutional symptoms, defined as any one or more of the following disease-related
 symptoms or signs:

 -  unintentional weight loss of 10% or more within the previous 6 months

 -  significant fatigue

 -  fevers higher than 100.5°F or 38.0°C for >=2 weeks without other evidence of infection

 -  night sweats for > 1 month without evidence of infection

 -  Clinically quantifiable disease burden defined as at least one of the following:

 -  either ALC >10 000/µL, or

 -  measurable lymphadenopathy

 -  quantifiable bone marrow infiltration documented in a bone marrow biopsy during
 screening

 -  Resolution of all clinically relevant acute non-hematologic toxic effects of any prior
 antitumor therapy resolved to Grade <=1

 -  Baseline laboratory data as defined as:

 Hemoglobin (Hb): >=8g/dL Absolute Neutrophil Count (ANC): >=1000/µL Platelet (PLT):
 >=25000/µL Glomerular Filtration Rate (GFR) or Creatinine Clearance: >=30ml/min Aspartate
 Aminotransferase (AST) and Alanine Aminotransferase (ALT): <3 x Upper Limit of Normal (ULN)
 Bilirubin - total: <1.5 x ULN Activated Partial Thromboplastin Time (aPTT), Prothrombin
 Time (PT) or International Normalized Ratio (INR): <=1.5 x ULN PT <=1.5 x ULN, INR <=1.5

 -  Male or female patients. Women of childbearing potential must agree to use highly
 effective methods of birth control during the trial and for at least 1 year after the
 last dose of BI 836826 and 1 month after the last dose of ibrutinib.

 -  Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2.

 -  Age 18 years and older

 -  Eligible and able to secure sourcing for ibrutinib

 -  Written Informed Consent

 -  Further Inclusion criteria apply

 Exclusion criteria:

 -  Known transformation of Chronic Lymphocytic Leukemia (CLL) to an aggressive B-cell
 malignancy at the time of screening

 -  Prior allogeneic stem cell transplant within one year or active graft vs. host
 disease.

 -  History of a non-CLL malignancy except for adequately treated in situ, stage 1 or 2
 carcinoma in Complete Response (CR), or any other cancer that has been in CR for >=2
 years after end of cancer treatment.

 -  Active, uncontrolled autoimmune cytopenia. Patients with autoimmune cytopenia which is
 controlled with corticosteroids at doses of <=20 mg prednisolone or equivalent may be
 enrolled.

 -  Previous CLL treatment with a CD37-targeting antibody or a CD37-antibody drug
 conjugate.

 -  Previous treatment with ibrutinib

 -  Previous treatment with another Bruton's Tyrosine Kinase (BTK) -inhibitor.

 -  Ongoing systemic immunosuppressive therapy other than corticosteroids.

 -  Active bacterial, viral, or fungal infection requiring systemic treatment at the time
 of study entry.

 -  Human Immunodeficiency Virus (HIV) infection

 -  Active hepatitis B or C as evidenced by detection of virus specific Deoxyribonucleic
 Acid (DNA) or Ribonucleic Acid (RNA).

 -  History of stroke or intracranial hemorrhage within 6 months prior to enrollment

 -  Chronic persistent atrial flutter or atrial fibrillation. Patients with intermittent
 atrial fibrillation may be enrolled if without episode for >= 6 months and without
 indication for anti-coagulation

 -  Requirement for chronic anticoagulation with warfarin or with direct oral
 anticoagulants at the time of screening.

 -  Chronic treatment (i.e. >7 days) with a strong Cytochrome P450 (CYP3A) inhibitor which
 cannot be terminated prior to the first dose of ibrutinib.

 -  Unstable angina pectoris, uncontrolled hypertension, uncontrolled asthma or other
 pulmonary disease

 -  Women who are pregnant, nursing, or who plan to become pregnant while in the trial

 -  Further Exclusion criteria apply