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

A Phase Ib, Open Label, Single Arm, Multi-center, Dose Escalation Trial of Intravenous BI 836826 in Combination With Ibrutinib in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia

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