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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Leukemia, Myeloid, Acute

Intervention / Treatment
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* Drug: Decitabine
* Drug: BI 836858


Participation Criteria
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Eligibility Criteria
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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: 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). Prior treatment with Cluster of differentiation 33 (CD33) antibody. Further exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase I: Dose Escalation<br>Combination treatment of decitabine with escalating doses of BI 836858 | Drug: Decitabine<br> <br> Drug: BI 836858<br> <br> |
| Experimental: Phase I: Extension<br>Cohort A treated with BI 836858 plus intensive decitabine treatment schedule. Followed by Cohort B treated with BI 836858 plus standard decitabine treatment schedule. | Drug: Decitabine<br> <br> Drug: BI 836858<br> <br> |
| Experimental: Phase II: Arm 1<br>Combination treatment of decitabine with BI 836858 | Drug: Decitabine<br> <br> Drug: BI 836858<br> <br> |
| Other: Phase II: Arm 2<br>Monotherapy treatment with decitabine (standard of care treatment) | Drug: Decitabine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Number of patients with dose limiting toxicity (DLT(s)) during first treatment cycle |  | 12 months | 
| Phase II:Number of patients with objective response combining - Complete remission (CR) - CR with incomplete blood count recovery (CRi) |  | 30 months | 
| Phase I: MTD of BI 836858 in combination with decitabine |  | 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase II: Event free survival (EFS) |  | 60 months | 
| Phase II: Relapse free survival (RFS) |  | 60 months | 
| Phase II: Remission duration |  | 60 months | 
| Phase II: Time to remission |  | 60 months | 
| Phase I: Number of patients with objective response combining - Complete remission (CR) - CR with incomplete blood count recovery (CRi) |  | 60 months |