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

NCT02632721 | Completed Phase 1 Results DMC

• 2 other identifiers: 1315.22015-002892-30
• Study Type: interventional
• Target: 49
• Locations: 4 countries
• Sites: 14

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.

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• 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.

Study Arms (5)

Phase I dose escalation: BI 836858 20 mg + decitabine (intensive)

EXPERIMENTAL

Dose escalation.

Drug: Decitabine; Drug: BI 836858

Phase I dose escalation: BI 836858 40 mg + decitabine (intensive)

EXPERIMENTAL

Dose escalation.

Drug: Decitabine; Drug: BI 836858

Phase I dose escalation: BI 836858 80 mg + decitabine (intensive)

EXPERIMENTAL

Dose escalation.

Drug: Decitabine; Drug: BI 836858

Phase I Extension A: BI 836858 80 mg + decitabine (intensive)

EXPERIMENTAL

Extension phase.

Drug: Decitabine; Drug: BI 836858

Phase I Extension B: BI 836858 80 mg + decitabine (standard)

EXPERIMENTAL

Extension phase.

Drug: Decitabine; Drug: BI 836858

Interventions

Decitabine DRUG

Phase I Extension A: BI 836858 80 mg + decitabine (intensive); Phase I Extension B: BI 836858 80 mg + decitabine (standard); Phase I dose escalation: BI 836858 20 mg + decitabine (intensive); Phase I dose escalation: BI 836858 40 mg + decitabine (intensive); Phase I dose escalation: BI 836858 80 mg + decitabine (intensive)

BI 836858 DRUG

Phase I Extension A: BI 836858 80 mg + decitabine (intensive); Phase I Extension B: BI 836858 80 mg + decitabine (standard); Phase I dose escalation: BI 836858 20 mg + decitabine (intensive); Phase I dose escalation: BI 836858 40 mg + decitabine (intensive); Phase I dose escalation: BI 836858 80 mg + decitabine (intensive)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• Acute promyelocytic leukemia (APL, French-American-British (FAB) subtype M3), according to WHO classification.
• Patients who are candidates for allogeneic stem cell transplantation.
• Active chronic graft versus host disease requiring immunosuppressive treatment.
• Phase I extension and Phase II only:
• Prior treatment with a hypomethylating agent, such as prior treatment for Myelodysplastic Syndrome (MDS).

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (14)

Mayo Clinic Cancer Center

Jacksonville, Florida, 32224, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Northwell Health

Lake Success, New York, 11042, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Universitätsklinikum Augsburg

Augsburg, 86156, Germany

Location

Vivantes Netzwerk für Gesundheit GmbH

Berlin, 10967, Germany

Location

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, 01307, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Universitätsklinikum Jena

Jena, 07740, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

A.O. Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Politècnic La Fe

Valencia, 46026, Spain

Location

Related Links

• Related Info

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Decitabine; BI 836858

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Limitations and Caveats

Sponsor stopped development of the study drug before Phase II start. Phase II was not performed.

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
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Model Details: Phase I Dose Escalation: Open-label, single-arm, dose escalation \- To determine the maximum tolerated dose (MTD) and the recommended dose for Phase I Extension (RExP1D) Phase I Extension: Open-label, two consecutive groups (cohort A and B) - To collect additional data on safety, pharmacokinetics and efficacy and to decide if the RExP1D will become the Recommended Phase II Dose (RP2D) Phase II: Open-label, two-arm randomized \- To investigate efficacy, safety and pharmacokinetics of BI 836858 in combination with decitabine compared to decitabine monotherapy

Study Record Dates

• First Submitted: December 15, 2015
• First Posted: December 17, 2015
• Study Start: June 16, 2016
• Primary Completion: January 16, 2023
• Study Completion: January 16, 2023
• Last Updated: March 19, 2024
• Results First Posted: March 19, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (6); ES (3); US (4); IT (1)