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

Phase 1

Completed

• Conditions: Leukemia, Lymphocytic, Chronic, B-Cell
• Interventions: Drug: BI 836826; Drug: Ibrutinib

• Registration Number: NCT02759016
• Lead Sponsor: Boehringer Ingelheim

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-04-27
• Study First Submitted QC: 2016-04-29
• Study First Posted: 2016-05-03
• Study Start: 2016-06-23
• Primary Completion: 2019-06-03
• Study Completion: 2019-07-09
• Results First Submitted: 2020-07-07
• Results First Submitted QC: 2020-07-07
• Results First Posted: 2020-07-24
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-08
• Last Update Posted: 2020-09-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BI 836826	Ibrutinib	BI 836826 administered in combination with Standard of Care Ibrutinib
BI 836826	BI 836826	BI 836826 administered in combination with Standard of Care Ibrutinib

Primary Outcome Measures

Name	Time	Method
Recommended Phase 2 Dose of BI 836826 in Combination With Ibrutinib	First treatment cycle, 4 weeks from first administration of BI 836826.	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.
Number of Participants With Dose Limiting Toxicities (DLTs) During the First Treatment Cycle	First treatment cycle, 4 weeks from first administration of BI 836826.	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.

Secondary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose of BI 836826 in Combination With Ibrutinib	First treatment cycle, 4 weeks from first administration of BI 836826.	To determine the Maximum Tolerated Dose (MTD) of BI 836826 in combination with ibrutinib, participants were entered sequentially into dose cohorts starting at 100 mg of BI 836826 and escalating to the MTD in combination with ibrutinib (fixed dose of 420 mg daily). Stepwise dose escalation of BI 836826 was guided by a Bayesian Logistic Regression Model (BLRM) with overdose control. The BLRM estimates the MTD by updating estimates of the probability of observing a Dose Limiting Toxicity (DLT) in the first treatment cycle (4 weeks) for each dose level as participant information becomes available. The MTD would be considered reached if the following criteria were fulfilled. The posterior probability of the true DLT rate in the target interval \[0.16 - 0.33) of the MTD is above 0.50 or at least 15 participants have been treated in the study, of which at least 6 at the MTD.

Trial Locations

Locations (3)

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Oregon Health and Sciences University; 🇺🇸 Portland, Oregon, United States

City of Hope; 🇺🇸 Duarte, California, United States