Volasertib in Japanese Patients With Acute Myeloid Leukemia (AML)

Study Overview
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Brief Summary
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To investigate safety, tolerability, maximum tolerated dose of volasertib in Japanese patients with AML

Official Title
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An Open Label, Phase I Trial of Intravenous Once Every 2 Weeks Administration of BI 6727 (Volasertib) in Japanese Patients With Acute Myeloid Leukemia

Conditions
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Leukemia, Myeloid, Acute

Intervention / Treatment
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* Drug: Volasertib


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients with diagnosis of AML (except for acute promyelocytic leukemia, APL) according to the World Health Organization definition and with one of the following features at screening Relapsed or refractory AML Untreated AML patients not considered to be suitable for standard induction therapy according to investigator's judgement Male or female patients of age >/= 18 years at the time of informed consent Eastern Cooperative Oncology Group performance status score 0 - 2 at screening Signed written informed consent consistent with Japanese Good Clinical Practice. Exclusion criteria: Patients with APL Patients in the third or later relapse Prior stem cell transplantation Treatment with systemic therapy for the primary disease (including an investigational drug) within 14 days before the first dose of volasertib with the exception of hydroxyurea, or lack of recovery from any acute toxicities or clinically significant adverse events pertinent to the prior systemic therapy Treatment with gemtuzumab ozogamicin within 6 weeks before the first dose of volasertib Concomitant medication/treatment with anti-leukemic chemotherapy (systemic or intrathecal), radiotherapy, immunotherapy, or any investigational agent while receiving study treatment Other malignancy requiring treatment at the time of screening Clinical central nervous system (CNS) symptoms deemed by the investigator to be related to leukemic CNS involvement or requiring treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Volasertib<br>Patient to receive escalating dose of volasertib | Drug: Volasertib<br>* Patient to receive volasertib<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicities (DLT) in Cycle 1 for the Determination of the Maximum Tolerated Dose (MTD) of Volasertib | Primary objective for this trial was to identify the MTD of volasertib. The MTD was defined as the highest dose level at which DLTs were reported in at most 2 in 6 evaluable patients during cycle 1. In this outcome measure the number of participants with DLTs in cycle 1 is presented. | From first administration of trial drug up to 28 days | 
| MTD of Volasertib | Primary objective for this trial was to identify the MTD of volasertib. The MTD was defined as the highest dose level at which DLTs were reported in at most 2 in 6 evaluable patients during cycle 1. In this outcome measure the MTD is presented. | From first administration of trial drug up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Response by Complete Remission (CR) | The secondary outcome best response will be presented by the CR, CR with incomplete blood count recovery (CRi) and partial remission (PR). In this outcome measure the CR will be presented. The criteria for the CR are: Bone marrow blasts less than 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) >1.0 × 10^9/Litre (L) (1000/microlitre (μL)); platelet count >100 × 10^9/L (100 000/μL); independence of red cell transfusions. | From first administration of trial drug up to 486 days | 
| Best Response by CRi | The secondary outcome best response will be presented by the CR, CRi and PR. In this outcome measure the CRi will be presented. The criteria for the CRi are: All CR criteria are met except for residual neutropenia (<1.0 × 10^9/L [1000/μL]) or thrombocytopenia (<100 × 10^9/L [100 000/μL]). | From first administration of trial drug up to 486 days | 
| Best Response by PR | The secondary outcome best response will be presented by the CR, CRi and PR. In this outcome measure the PR is presented. The criteria for the PR are: All haematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%. | From first administration of trial drug up to 486 days | 
| Remission Duration | The remission duration is the time from the date of achieving CR or CRi until relapse for patients with documented CR or CRi. | From first administration of trial drug up to 486 days |