Clinical trial NCT02759016: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia, Lymphocytic, Chronic, B-Cell
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2016-05-03
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Recommended Phase 2 Dose of BI 836826 in Combination With Ibrutinib
timeFrame: First treatment cycle, 4 weeks from first administration of BI 836826.
measure: Number of Participants With Dose Limiting Toxicities (DLTs) During the First Treatment Cycle
timeFrame: First treatment cycle, 4 weeks from first administration of BI 836826.
Secondary outcomes:
measure: Maximum Tolerated Dose of BI 836826 in Combination With Ibrutinib
timeFrame: First treatment cycle, 4 weeks from first administration of BI 836826.
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Portland
country: United States
facility: Oregon Health and Sciences University
state: Oregon
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: