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

Leukemia, Myeloid, Acute Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02632721
• Other study ID #: 1315.2
• Secondary ID: 2015-002892-30
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 16, 2016
• Est. completion date: January 16, 2023

Study information

• Verified date: February 2024
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: January 16, 2023
• Est. primary completion date: January 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Decitabine

• BI 836858

Locations

Country	Name	City	State
Germany	Universitätsklinikum Augsburg	Augsburg
Germany	Vivantes Netzwerk für Gesundheit GmbH	Berlin
Germany	Universitätsklinikum Carl Gustav Carus Dresden	Dresden
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitätsklinikum Jena	Jena
Germany	Universitätsklinikum Münster	Münster
Italy	A.O. Spedali Civili di Brescia	Brescia
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Politècnic La Fe	Valencia
United States	Northwestern University	Chicago	Illinois
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Mayo Clinic Cancer Center	Jacksonville	Florida
United States	Northwell Health	Lake Success	New York

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).
Primary	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	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.

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