A Trial to Find and Investigate a Safe Dose of BI 836858 in Combination With Decitabine for Patients With Acute Myeloid Leukemia (AML)

An Open-label, Phase I/II Trial to Determine the Maximum Tolerated Dose and Investigate Safety, Pharmacokinetics and Efficacy of BI 836858 in Combination With Decitabine in Patients With Acute Myeloid Leukemia

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.

Study Overview

• Status: Completed
• Conditions: Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: Decitabine; Drug: BI 836858

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Augsburg, Germany, 86156
    • Universitätsklinikum Augsburg
  • Berlin, Germany, 10967
    • Vivantes Netzwerk für Gesundheit GmbH
  • Dresden, Germany, 01307
    • Universitatsklinikum Carl Gustav Carus Dresden
  • Hamburg, Germany, 20246
    • Universitatsklinikum Hamburg-Eppendorf
  • Jena, Germany, 07740
    • Universitatsklinikum Jena
  • Münster, Germany, 48149
    • Universitatsklinikum Munster
• Italy
  • Brescia, Italy, 25123
    • A.O. Spedali Civili di Brescia
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Valencia, Spain, 46026
    • Hospital Politècnic La Fe
• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • New York
    • Lake Success, New York, United States, 11042
      • Northwell Health
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1)

Phase I Dose Escalation:

• Male or female patients >/= 18 years of age with relapsed or refractory AML
• Male or female patients >/= 65 years of age with previously untreated AML ineligible for receiving standard intensive therapy

Phase I Extension and Phase II:

-- Male or female patients >/= 65 years of age with previously untreated AML ineligible for receiving standard intensive therapy

2) Histologically or cytologically confirmed AML according to the WHO classification 3) Patients must be eligible for treatment with decitabine 4) Eastern co-operative oncology group (ECOG) performance score </=2 at screening Further inclusion criteria apply.

Exclusion criteria:

1. Acute promyelocytic leukemia (APL, French-American-British (FAB) subtype M3), according to WHO classification.
2. Patients who are candidates for allogeneic stem cell transplantation.
3. Active chronic graft versus host disease requiring immunosuppressive treatment.

4. Phase I extension and Phase II only:

   Prior treatment with a hypomethylating agent, such as prior treatment for Myelodysplastic Syndrome (MDS).

5. Prior treatment with Cluster of differentiation 33 (CD33) antibody. Further exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I dose escalation: BI 836858 20 mg + decitabine (intensive); Dose escalation.	Drug: Decitabine; Drug: BI 836858
Experimental: Phase I dose escalation: BI 836858 40 mg + decitabine (intensive); Dose escalation.	Drug: Decitabine; Drug: BI 836858
Experimental: Phase I dose escalation: BI 836858 80 mg + decitabine (intensive); Dose escalation.	Drug: Decitabine; Drug: BI 836858
Experimental: Phase I Extension A: BI 836858 80 mg + decitabine (intensive); Extension phase.	Drug: Decitabine; Drug: BI 836858
Experimental: Phase I Extension B: BI 836858 80 mg + decitabine (standard); Extension phase.	Drug: Decitabine; Drug: BI 836858

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I: Number of Patients With Dose Limiting Toxicity (DLT(s)) During 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 Investigator	Up to 28 days (first treatment cycle).
Phase I: Maximum Tolerated Dose (MTD) of BI 836858 in Combination With Decitabine	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.	From first drug administration until end of treatment, up to 941 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Number of Patients With Objective Response (CR + CRi)	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]).	From start of treatment until the earliest of progression, death or end of trial, up to 971 days.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2016
• Primary Completion (Actual): January 16, 2023
• Study Completion (Actual): January 16, 2023

Study Registration Dates

• First Submitted: December 15, 2015
• First Submitted That Met QC Criteria: December 15, 2015
• First Posted (Estimated): December 17, 2015

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: February 19, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine
• Other Study ID Numbers: 1315.2; 2015-002892-30 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:

1. studies in products where Boehringer Ingelheim is not the license holder;
2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).

For more details refer to: https://www.mystudywindow.com/msw/datasharing