A Trial to Find and Investigate a Safe Dose of BI 836858 in Combination With Decitabine for Patients With Acute Myeloid Leukemia (AML)
- Registration Number
- NCT02632721
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
Phase I Dose Escalation:
Primary objective is to determine the Maximum Tolerated Dose (MTD) and the recommended dose for Phase I Extension.
Secondary objective is to investigate the safety, pharmacokinetics and efficacy of BI 836858 in combination with decitabine
Phase I Extension:
Primary objective is to collect additional data on safety, pharmacokinetics and efficacy and to define the Recommended Phase II Dose (RP2D) of BI 836858 in combination with decitabine.
Phase II: Primary objective is to investigate efficacy, safety and pharmacokinetics of BI 836858 in combination with decitabine compared to decitabine monotherapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 49
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase I Extension B: BI 836858 80 mg + decitabine (standard) BI 836858 Extension phase. Phase I dose escalation: BI 836858 20 mg + decitabine (intensive) BI 836858 Dose escalation. Phase I dose escalation: BI 836858 40 mg + decitabine (intensive) Decitabine Dose escalation. Phase I dose escalation: BI 836858 40 mg + decitabine (intensive) BI 836858 Dose escalation. Phase I dose escalation: BI 836858 80 mg + decitabine (intensive) Decitabine Dose escalation. Phase I dose escalation: BI 836858 80 mg + decitabine (intensive) BI 836858 Dose escalation. Phase I Extension A: BI 836858 80 mg + decitabine (intensive) BI 836858 Extension phase. Phase I dose escalation: BI 836858 20 mg + decitabine (intensive) Decitabine Dose escalation. Phase I Extension A: BI 836858 80 mg + decitabine (intensive) Decitabine Extension phase. Phase I Extension B: BI 836858 80 mg + decitabine (standard) Decitabine Extension phase.
- Primary Outcome Measures
Name Time Method Phase I: Number of Patients With Dose Limiting Toxicity (DLT(s)) During First Treatment Cycle Up to 28 days (first treatment cycle). Number of patients with dose limiting toxicity (DLT(s)) for BI 836858 in combination with decitabine during first treatment cycle (Phase 1).
DLT was defined as any non-disease-related non-haematological adverse event (AE) of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher. Expected non-haematological disease-related AEs were not to be regarded as a DLT.
These included complications resulting from haematological AEs such as:
* Bleeding and complications from bleeding due to thrombocytopenia as defined by the Investigator,
* Infection and complications from infections due to neutropenia as defined by the Investigator,
* Constitutional symptoms due to anaemia as defined by the InvestigatorPhase I: Maximum Tolerated Dose (MTD) of BI 836858 in Combination With Decitabine From first drug administration until end of treatment, up to 941 days. The Maximum tolerated dose (MTD) of BI 836858 in combination with decitabine was estimated after the dose escalation part of the trial obtaining on the basis of dose limiting toxicities (DLT(s)) observed during the first treatment cycle. However, for those patients who receive more than one cycle of the combination treatment, all adverse events that constitute a DLT will be considered for re-estimation of the MTD based on the Bayesian logistic regression model (BLRM). The MTD is defined as the highest dose of BI 836858 (in combination with decitabine) with less than 25% risk of the true DLT rate being above 33% during the MTD evaluation period.
- Secondary Outcome Measures
Name Time Method Phase 1: Number of Patients With Objective Response (CR + CRi) From start of treatment until the earliest of progression, death or end of trial, up to 971 days. Number of patients with objective response (Complete remission (CR) + complete remission with incomplete remission (CRi)).
CR was defined as bone marrow (BM) blasts \< 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count \> 1.0 x 109/L \[1,000/μL\]; platelet count \> 100 x 109/L \[100,000/μL\]; independence of red blood cells transfusions (no transfusion for 1 week prior to the assessment). No minimum duration of response is required.
CRi was defined as all CR criteria except for residual neutropenia (\< 1.0 x 109/L \[1,000/μL\]) or thrombocytopenia (\< 100 x 109/L \[100,000/μL\]).
Trial Locations
- Locations (14)
Northwestern University
🇺🇸Chicago, Illinois, United States
Mayo Clinic Cancer Center
🇺🇸Jacksonville, Florida, United States
Vivantes Netzwerk für Gesundheit GmbH
🇩🇪Berlin, Germany
Hospital Politècnic La Fe
🇪🇸Valencia, Spain
Universitätsklinikum Augsburg
🇩🇪Augsburg, Germany
Universitätsklinikum Münster
🇩🇪Münster, Germany
A.O. Spedali Civili di Brescia
🇮🇹Brescia, Italy
Universitätsklinikum Jena
🇩🇪Jena, Germany
Northwell Health
🇺🇸Lake Success, New York, United States
Universitätsklinikum Carl Gustav Carus Dresden
🇩🇪Dresden, Germany
Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Hospital Clínic de Barcelona
🇪🇸Barcelona, Spain
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States