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

Boehringer Ingelheim

Status and phase

Completed

Phase 1

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Treatments

Drug: BI 836826

Drug: Ibrutinib

Study type

Interventional

Funder types

Industry

Identifiers

NCT02759016

1270.15

Details and patient eligibility

About

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

Enrollment

7 patients

Sex

All

Ages

18 to 99 years old

Volunteers

No Healthy Volunteers

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