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
Condition: Leukemia, Lymphocytic, Chronic, B-Cell
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: BI 836826; Ibrutinib
Intervention description: Standard of Care
Intervention MeSH terms: BI 836826
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No

Summary:

      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
    

Eligibility criteria:

        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