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

NCT02759016 | Completed Phase 1 Results

• 1 other identifier: 1270.15
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 3

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

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Outcome Measures

Primary Outcomes (2)

• Recommended Phase 2 Dose of BI 836826 in Combination With Ibrutinib

  The Recommended Phase 2 Dose (RP2D ) of BI 836826 in combination with ibrutinib would be either the Maximum Tolerated Dose (MTD) or a lower dose and would be determined by the safety review committee based on safety and efficacy considerations.

  First treatment cycle, 4 weeks from first administration of BI 836826.

• Number of Participants With Dose Limiting Toxicities (DLTs) During the First Treatment Cycle

  Number of participants with Dose Limiting Toxicities (DLTs) during the first treatment cycle. DLT was defined as any non-hematologic adverse event (AE) of Grade ≥ 3 related to BI 836826 and/or ibrutinib except infusion-related reaction (any Grade), Grade 3 Aspartate Aminotransferase (AST)- and/or Alanine Aminotransferase (ALT) elevation without concomitant bilirubin, elevation or any other asymptomatic Grade 3 laboratory abnormality with spontaneous recovery within 1 week. The following hematologic AEs related to BI 836826 and/or ibrutinib were considered DLT: Grade 4 neutropenia with concomitant infection, Grade 4 febrile neutropenia, and Grade 3 febrile neutropenia not resolving within 72 hours with appropriate treatment (antibiotics, antivirals, antifungals, growth factor support), Grade 4 thrombocytopenia with clinically significant bleeding, Grade 4 anemia, any Grade 5 hematologic AE.

  First treatment cycle, 4 weeks from first administration of BI 836826.

Secondary Outcomes (1)

• Maximum Tolerated Dose of BI 836826 in Combination With Ibrutinib

  First treatment cycle, 4 weeks from first administration of BI 836826.

Study Arms (1)

BI 836826

EXPERIMENTAL

BI 836826 administered in combination with Standard of Care Ibrutinib

Drug: BI 836826; Drug: Ibrutinib

Interventions

BI 836826 DRUG

BI 836826

Ibrutinib DRUG

Standard of Care

BI 836826

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (3)

City of Hope

Duarte, California, 91010, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Oregon Health and Sciences University

Portland, Oregon, 97239, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

BI 836826; ibrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Development of BI 836826 was discontinued (strategic decision). Recruitment was subsequently terminated, the Phase II part of the trial was eliminated from the protocol, participants on treatment were allowed to complete the trial as per protocol.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2016
• First Posted: May 3, 2016
• Study Start: June 23, 2016
• Primary Completion: June 3, 2019
• Study Completion: July 9, 2019
• Last Updated: September 29, 2020
• Results First Posted: July 24, 2020

Record last verified: 2020-09

Locations

US (3)