In patients with haemoglobin counts below the limits of normal at baseline, improvement in this count during therapy potentially indicated a benefit for the patient. Number of patients with improved haemoglobin count for at least two subsequent response assessments which fulfil International Workshop on Chronic Lymphocytic Leukemia (IWCLL) response criteria for Complete Remission (CR) or Partial Remission (PR). The response was assessed before Progressive Disease (PD) or start of new Chronic Lymphocytic Leukaemia (CLL) therapy.

In patients with platelet counts below the limits of normal at baseline, improvement in this count during therapy potentially indicated a benefit for the patient. Number of patients with improved platelet count for at least two subsequent response assessments which fulfil International Workshop on Chronic Lymphocytic Leukemia (IWCLL) response criteria for Complete Remission (CR) or Partial Remission (PR). The response was assessed before Progressive Disease (PD) or start of new Chronic Lymphocytic Leukaemia (CLL) therapy.

In patients with neutrophil count below the limits of normal at baseline, improvement in this count during therapy potentially indicated a benefit for the patient. Number of patients with improved neutrophil count for at least two subsequent response assessments which fulfil International Workshop on Chronic Lymphocytic Leukemia (IWCLL) response criteria for Complete Remission (CR) or Partial Remission (PR). The response was assessed before Progressive Disease (PD) or start of new Chronic Lymphocytic Leukaemia (CLL) therapy.

Response was assessed according to the IWCLL (International Workshop on Chronic Lymphocytic Leukemia) guidelines based on laboratory data from the peripheral blood and clinical examination by the investigator after each cycle prior to administration of the next dose of BI 836826, at the end of the treatment (EOT) visit, and at all Follow-up Visits. Best overall response will be analysed descriptively. Frequency distributions will be used to examine this endpoint.

Progression-free survival (PFS) was defined as the time from the first administration of BI 836826 until disease progression or death, whichever occurred first. Disease progression= At least one of the following:

• 50+% increase in blood lymphocytes over baseline with an absolute number of B-lymphocytes of at least 5x109/L
• Progression of lymphadenopathy
• 50+% increase in the previously noted enlargement of the liver or new appearance of hepatomegaly
• 50+% increase in the previously noted enlargement of the spleen or new appearance of splenomegaly
• 50+% Decrease of platelet counts or to less than 100x109/L secondary to CLL and unrelated to autoimmune cytopenia
• Decrease of haemoglobin levels by more than 20 g/L, or to less than 100 g/L secondary to CLL and unrelated to autoimmune cytopenia T Transformation to a more aggressive histology, e.g. Richter syndrome.

Failure-free survival (FFS) was defined as the time from the first administration of BI 836826 until disease progression or death, or start of next Chronic Lymphocytic Leukemia (CLL) therapy, whichever occurred first. Disease progression= At least one of the following:

• 50+% increase in blood lymphocytes over baseline with an absolute number of B-lymphocytes of at least 5x109/L
• Progression of lymphadenopathy
• 50+% increase in the previously noted enlargement of the liver or new appearance of hepatomegaly
• 50+% increase in the previously noted enlargement of the spleen or new appearance of splenomegaly
• 50+% Decrease of platelet counts or to less than 100x109/L secondary to CLL and unrelated to autoimmune cytopenia
• Decrease of haemoglobin levels by more than 20 g/L, or to less than 100 g/L secondary to CLL and unrelated to autoimmune cytopenia T Transformation to a more aggressive histology, e.g. Richter syndrome.

Patients were administered BI 836826-9 milligram solution for infusion after dilution intravenously as one or two doses within the first cycle followed by single doses within all following 14-day cycles

Patients were administered BI 836826-25 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles

Patients were administered BI 836826-50 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles

Patients were administered BI 836826-100 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles

Patients were administered BI 836826-200 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles

Patients were administered BI 836826-400 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles

Patients were administered BI 836826-800 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles

Total of all reporting groups

Ethnicity data were not collected for the study. Race was not collected in France due to law (These are the missing/unknown).

Patients were administered BI 836826-3 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle

Patients were administered BI 836826-9 milligram solution for infusion after dilution intravenously as one or two doses within the first cycle followed by single doses within all following 14-day cycles

Patients were administered BI 836826-25 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles

Patients were administered BI 836826-50 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles

Patients were administered BI 836826-100 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles

Patients were administered BI 836826-200 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles

Patients were administered BI 836826-400 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles

Patients were administered BI 836826-800 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles

In patients with haemoglobin counts below the limits of normal at baseline, improvement in this count during therapy potentially indicated a benefit for the patient. Number of patients with improved haemoglobin count for at least two subsequent response assessments which fulfil International Workshop on Chronic Lymphocytic Leukemia (IWCLL) response criteria for Complete Remission (CR) or Partial Remission (PR). The response was assessed before Progressive Disease (PD) or start of new Chronic Lymphocytic Leukaemia (CLL) therapy.

Treated Set (TS): All patients who received at least one application of the drug BI 836826.

In patients with platelet counts below the limits of normal at baseline, improvement in this count during therapy potentially indicated a benefit for the patient. Number of patients with improved platelet count for at least two subsequent response assessments which fulfil International Workshop on Chronic Lymphocytic Leukemia (IWCLL) response criteria for Complete Remission (CR) or Partial Remission (PR). The response was assessed before Progressive Disease (PD) or start of new Chronic Lymphocytic Leukaemia (CLL) therapy.

TS

In patients with neutrophil count below the limits of normal at baseline, improvement in this count during therapy potentially indicated a benefit for the patient. Number of patients with improved neutrophil count for at least two subsequent response assessments which fulfil International Workshop on Chronic Lymphocytic Leukemia (IWCLL) response criteria for Complete Remission (CR) or Partial Remission (PR). The response was assessed before Progressive Disease (PD) or start of new Chronic Lymphocytic Leukaemia (CLL) therapy.

TS

Response was assessed according to the IWCLL (International Workshop on Chronic Lymphocytic Leukemia) guidelines based on laboratory data from the peripheral blood and clinical examination by the investigator after each cycle prior to administration of the next dose of BI 836826, at the end of the treatment (EOT) visit, and at all Follow-up Visits. Best overall response will be analysed descriptively. Frequency distributions will be used to examine this endpoint.

TS

Progression-free survival (PFS) was defined as the time from the first administration of BI 836826 until disease progression or death, whichever occurred first. Disease progression= At least one of the following:

• 50+% increase in blood lymphocytes over baseline with an absolute number of B-lymphocytes of at least 5x109/L
• Progression of lymphadenopathy
• 50+% increase in the previously noted enlargement of the liver or new appearance of hepatomegaly
• 50+% increase in the previously noted enlargement of the spleen or new appearance of splenomegaly
• 50+% Decrease of platelet counts or to less than 100x109/L secondary to CLL and unrelated to autoimmune cytopenia
• Decrease of haemoglobin levels by more than 20 g/L, or to less than 100 g/L secondary to CLL and unrelated to autoimmune cytopenia T Transformation to a more aggressive histology, e.g. Richter syndrome.

TS

Failure-free survival (FFS) was defined as the time from the first administration of BI 836826 until disease progression or death, or start of next Chronic Lymphocytic Leukemia (CLL) therapy, whichever occurred first. Disease progression= At least one of the following:

• 50+% increase in blood lymphocytes over baseline with an absolute number of B-lymphocytes of at least 5x109/L
• Progression of lymphadenopathy
• 50+% increase in the previously noted enlargement of the liver or new appearance of hepatomegaly
• 50+% increase in the previously noted enlargement of the spleen or new appearance of splenomegaly
• 50+% Decrease of platelet counts or to less than 100x109/L secondary to CLL and unrelated to autoimmune cytopenia
• Decrease of haemoglobin levels by more than 20 g/L, or to less than 100 g/L secondary to CLL and unrelated to autoimmune cytopenia T Transformation to a more aggressive histology, e.g. Richter syndrome.

TS

Dose-Limiting Toxicities (DLTs) were defined as any drug-related non-haematologic adverse event of Common Terminology Criteria for AE (CTCAE) Grade 3 or higher, except infusion related reactions associated with the administration of BI 836826. In addition complications due to haematologic AEs were considered as DLTs and were added in more detail in an amendment later on.

The maximum tolerated dose (MTD) evaluation set: This includes all patients who were documented to have received at least one dose of trial medication and were not replaced for the MTD evaluation.

The maximum tolerated dose (MTD) was defined as the highest dose of BI 836826 studied for which the incidence of DLT was no more than 17% (i.e. 1 out of 6 patients) during the first treatment cycle. For those patients who received more than 1 cycle of BI 836826, all AEs corresponding to the DLT were considered for the purpose of confirming the MTD and for the selection of the recommended dose for treatment of the expansion cohort and for further development. All DLTs, occurring during the first or repeated treatment cycle were reported as significant AEs. As it was not possible to recruit a sufficient number of patients whilst the first part of the trial was still in progress, the recruitment was ended by the sponsor before the MTD or optimal biological dose (OBD) was reached.

The trial was discontinued prematurely due to lack of recruitment before the MTD based on the frequency of patients with DLTs in the first treatment cycle was reached.

Patients were administered BI 836826-3 milligram solution for infusion after dilution intravenously as one single dose within a 14-day cycle

Patients were administered BI 836826-9 milligram solution for infusion after dilution intravenously as one or two doses within the first cycle followed by single doses within all following 14-day cycles

Patients were administered BI 836826-25 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles

Patients were administered BI 836826-50 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles

Patients were administered BI 836826-100 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles

Patients were administered BI 836826-200 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles

Patients were administered BI 836826-400 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles

Patients were administered BI 836826-800 milligram solution for infusion after dilution intravenously as two doses within the first cycle followed by single doses within all following 14-day cycles