Study Evaluating Orally Administered AMG 900 in Adult Subjects With Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This study of AMG 900 will be conducted in two parts: dose escalation and dose expansion. The dose escalation part of the study is aimed at evaluating the safety, tolerability and PK (pharmacokinetics) of oral AMG 900 in subjects with acute myeloid leukemia. Up to 93 subjects may be enrolled in dose escalation. The dose expansion part of the study will consist of 20 subjects with acute myeloid leukemia. The dose of AMG 900 will be dependent upon data from the dose escalation part of the study.

Official Title
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A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally Administered AMG 900 in Adult Subjects With Acute Myeloid Leukemia

Conditions
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Cancer, Hematologic Malignancies, Leukemia, Myeloid Leukemia

Intervention / Treatment
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* Drug: Arm 1- Dose Escalation
* Drug: Arm 2- Dose Expansion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women ≥ 18 years old Pathologically documented, definitively diagnosed AML that has failed standard treatments or for which no standard therapy is available or the subject refuses standard therapy Must consent to undergo bone marrow biopsies per schedule of assessments Exclusion Criteria: White blood cell greater than 20,000 uL History of or active central nervous system leukemia Prior allogeneic bone marrow transplant Subject will not be available for protocol-required study visits or procedures Other Inclusion/ Exclusion Criteria may apply to qualify for enrollment

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1- Dose Escalation<br>The dose escalation will be conducted in 2 parts. Group 1 will consist of 8 cohorts and Group 2 will consist of 5 cohorts. The dose escalation is aimed at determining the maximum tolerated dose (MTD) of AMG 900. | Drug: Arm 1- Dose Escalation<br>* AMG 900 is a small molecule aurora kinase inhibitor. AMG 900 will be administered daily for 4 days every 2 weeks or daily 7 days every 2 weeks (ie.g., 4 consecutive days of dosing followed by 10 consecutive days off treatment).<br>|
| Experimental: Arm 2- Dose Expansion<br>The dose expansion part of the study will begin after completion of the dose escalation phase and will consist of 20 subjects with acute myelogenous leukemia. | Drug: Arm 2- Dose Expansion<br>* AMG 900 is a small molecule aurora kinases inhibitor. The dose expansion phase would be conducted to gain further clinical experience with AMG 900 in AML at the optimal dose schedule.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject incidence of adverse events |  | 1 year | 
| Subject incidence of dose limiting toxicities (DLTs) |  | 1 year | 
| Maximum observed concentration of AMG 900 |  | 1 year | 
| Time to maximum observed concentration of AMG 900 |  | 1 year | 
| Area under the plasma concentration-time curve (AUC) of AMG 900 |  | 1 year | 
| Half life of AMG 900 |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response as per Cheson Response Criteria |  | 1 year | 
| Change in the number of p-Histone H3 positive cells from baseline |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amgen, Phase 1, Clinical Trial, Aurora kinase inhibitor, Open label, Oncology, Hematology